The BK polyomavirus was isolated in 1971; it has been a significant risk factor for both graft dysfunction and failure in renal transplant recipients. So far, no specific treatment option has been available for effective treatment or prophylaxis for BK virus infections. Although the use of heavy immunosuppression has been the main risk factor for BK virus infection, other risk factors are equally important, including elderly recipients, prior rejection episodes, male sex, human leukocyte antigen mismatching, prolonged cold ischemia time, pretransplant BK virus serostatus, and ureteral stenting. Regular follow-up for BK virus infections according to each institution’s policy has been, so far, effective in detecting patients with BK virus viremia and consequently preventing allograft loss. The mainstay of management continues to be reduction of immunosuppression. However, newer options are providing new insights, such as cellular immunotherapy. In this review, we will address the diagnosis, screening, new diagnostic tools, and updated management of BK virus infections.

Key words : Graft dysfunction, Immunosuppression, Polyomavirus, Renal failure

Introduction

Polyomaviruses are small DNA viruses that can infect humans and animals like rabbits, rodents, and birds. BK polyomavirus (BKV) is considered one of the highly prevalent forms of polyomaviruses causing infection in humans, especially in immuno­compromised patients. In renal transplant recipients, BKV can lead to tubulointerstitial nephritis and ureteral stenosis; it can also lead to hemorrhagic cystitis in bone marrow transplant patients.¹ The current consensus on management of BKV viremia is to decrease immunosuppression, to have regular follow-up of BKV polymerase chain reaction (PCR), and to have continuous monitoring of renal functions in an attempt to prevent allograft BKV nephropathy (BKVN), which could subsequently increase the risk of graft failure. The challenging part in the management of BKV infection is the balance between the fear of rejection due to reduction of immunosuppression and the maintenance of immunosuppression at the same level, which could cause more BKV viremia and consequently BKVN.²

BK virus is one of the most common infections in renal transplant recipients.^3-5 Every institution has its own local policy for screening BKV infection; however, most institutions tend to reduce immunosuppression to control BKV viremia, with few institutions following a preemptive immunosuppression reduction policy.^6-8 Reports have shown that BKVN management with reduction of immunosuppression has been effective in preserving allograft function.^9,10

Virology
Properties
BK virus is a member of the family Polyomaviruses. This family is a double-stranded DNA virus with icosahedral symmetry. BK virus has been categorized serologically and genotypically into 4 groups (I to IV), with each one having a different virulence.¹¹

Historical aspects
In 1971, a Sudanese renal transplant patient “whose initials were given for the virus” was diagnosed with BKV infection when he presented with ureteral obstruction after renal transplant. When the ureters were examined under electron microscopy, viral particles were seen in the lining of the ureters. In addition, a high BKV antibody titer was detected in the patient’s serum.¹²

Genome structure and transcription
Polyomaviruses are small (40-50 nm in diameter), uncovered, icosahedrals, with a double circular chain. Their genome is about 5000 base pairs, contained in the histones derived from host cells. When exposed to high temperature, their particles are stable, thus retaining their ability to infect. The external layer consists of structural proteins VP1, VP2, and VP3. VP1 is organized into 72 pentamers, each one associated with a unique copy of smaller structure proteins (VP2 or VP3). VP1 determines receptor specificity, whereas VP2 and VP3 are involved in viral particle stabilization outside the host cell and transport within it. The genomic structure encodes 6 chief proteins divided into 3 regions: early encoding region, late encoding region, and noncoding control region.¹³

Transmission mechanism
Primary BKV infection occurs in the first decade of life, on average at 4 to 5 years of age. Possible routes include the following: (1) airborne transmission through air droplets¹⁴; (2) a feco-oral transmission, as fecally eliminated polyomaviruses are detected in hospitalized children; (3) other mechanisms, including urinary-oral route or seroconversion after solid-organ transplant (such as renal transplantation)15; and (4) both through blood transfusion and vertical transmission; these have been considered routes for BKV transmission as BKV DNA has been found in the placenta, brain, and renal tissue of aborted fetuses.^16,17

Primary polyomavirus infections usually occur during childhood through respiratory or oral routes.¹⁸ Primary infections are often clinically insignificant; however, the virus stays in the renal epithelium, including in tubular, parietal, and transitional structures and in Bowman’s capsule.¹⁹ In the immunocompetent population, BKV replication is manifested by asymptomatic viruria, and the incidence of shedding is 20%. However, in immunocompromised individuals, the risk of shedding reaches 60% and the viruria is more common.^20,21 Patients with impaired cell-mediated immunity have a particularly greater risk of BKV infection; these patients include pregnant women where viral shedding usually disappears 2 weeks after delivery.²² The mean prevalence of BKVN in renal transplant recipients is 5%, whereas the prevalence of ureteral stenosis is less.²³

Risk factors and pathogenesis
The most important risk factor for developing BKV disease is the degree of immunosuppression rather than the type of immunosuppression used. Transplant physicians consider BKV infection as a marker of heavy immunosuppression.²⁴ Active BKV disease has been associated with various immunosuppression protocols, most commonly tacrolimus and mycophe­nolate mofetil based.^25,26 Other studies have suggested that BKV disease can occur with any immunosup­pression medication.^27,28 In addition, immunosup­pressive agents can affect T cells, which can lead to increased BKV replication. Tacrolimus specifically can increase BKV replication by a specific mechanism involving FK-binding protein (BP-12).²⁹ Other risk factors that could be involved, although not commonly, include diabetes mellitus, delayed graft function, treated episodes of acute rejection, ureteral trauma, use of antilymphocyte antibodies, coinfection with Cytomegalovirus (CMV), maintenance steroid immunosuppression, older age, white race/ethnicity, and presence of specific human leukocyte antigen (HLA) C loci.^30-32 Of note, the presence of BKV antibody titers in donors, which reflects recent BKV reactivation and replication, is another risk factor. The viruria in a potential donor can be considered as a predictor for posttransplant BKV infection.

Recent studies have demonstrated that BKV replication in a transplant recipient is usually due to transmitted infection from the donor.³⁰ Both HLA and ABO-incompatible transplants carry a higher risk of BKV nephropathy, possibly due to heavy immunosuppression (whether due to induction or maintenance immunosuppression or episodes of rejection). In 2004, Awadalla and associates demonstrated that renal transplant recipients who have HLA-incompatible transplant have increased incidence of rejection; this is especially shown in patients who were steroid resistant or treated with antilymphocyte treatment.³³ Similarly, ABO-incompatible recipients are at a higher risk of BKVN than HLA-mismatched recipients as they may have a higher rate of rejection and need more immuno­suppression than HLA-incompatible patients. In a study that compared 62 ABO-incompatible and 221 HLA-incompatible kidney transplant recipients, 17.7% versus 5.9% recipients developed BKVN, respectively.³²

Clinical Picture of BK Virus Infection
About 90% of the population will become BKV seropositive during their life; this reactivates after solid-organ transplant, especially in bone marrow or kidney transplant recipients. In kidney transplant recipients, reactivation may lead to BKVN, which may end with graft dysfunction and failure by causing tubulointerstitial nephritis and/or ureteral obstruction. In bone marrow transplant recipients, BKV can lead to hemorrhagic cystitis. It is quite rare to have BKV reactivation in other immuno­compromised patients, such as those with human immunodeficiency virus, systemic lupus, or other autoimmune diseases (Table 1).

Clinical manifestations are as follows: (1) asymptomatic, (2) slow and progressive increase of serum creatinine, and (3) an unsuspected finding of progressive renal damage (BKVN) on surveillance renal allograft biopsy.34 Importantly, no signs and symptoms are identified with BKV infection. Usually, BKV infection occurs 10 to 13 months posttransplant. BK virus nephropathy may occur earlier at week 1 posttransplant or as late as 5 years posttransplant.³⁵

Laboratory findings in patients with BKV infec­tion are as follows: (1) elevated serum creatinine and (2) urine analysis with pyuria, hematuria, and findings consistent with interstitial nephritis as cellular casts composed of renal tubular cells and inflammatory cells. However, these results could be normal.

Diagnosis Overview
A tissue (renal) biopsy is needed for a definitive diagnosis of BKVN; however, a diagnosis may be missed in the tissue obtained because viropathic lesions are patchy. In addition, for BKV, tropism is medulla, not the cortex, which may increase the risk of missing the viropathic lesions. Quantitative PCR is used to diagnose BKV viremia, which demonstrates BKV replication whether there is renal involvement or not. BK virus nephritis is suspected when the clinical diagnosis of tubulointerstitial nephritis is suspected; however, there are no clinical features of tubulointerstitial nephritis that are unique to BKVN. The presence of decoy cells in the urine analysis increases the suspicion of BKV nephritis, which should be followed by quantitative PCR of blood preferable to urine (Figure 1).

Different pathological patterns and associations with BKV infection are also shown in Figures 2 to 7.

Definitive diagnosis of BK virus nephropathy
A definitive diagnosis of BKVN requires characteristic cytopathic changes on the renal biopsy plus positive immunohistochemistry (against BKV or against SV40 large T antigens), which has a specificity of 100%, and pathognomonic results for BKV infection (Figure 6).36,37 A diagnosis of BKV in a renal biopsy could be missed in about 30% of cases because BKV has a focal tropism in the medulla rather than in the cortex, making an initial biopsy not enough to exclude the diagnosis of BKVN if highly suspicious.38,39 In the absence of definitive criteria for BKVN diagnosis (Table 2), a presumptive diagnosis can be done if there is sustained (more than 2-week duration) urinary viral shedding and significant BKV replication (plasma DNA PCR load > 10 000 copies/mL), as detected using a specific assay with or without kidney dysfunction; these characteristics have been proposed to define presumptive BKVN.36,38 Moreover, BKVN can be graded into 3 grades using Banff criteria according to the percentage of fibrosis and the amount of viral replication (Table 3).

In BKVN, light microscopy examinations would show the following: (1) basophilic intranuclear viral inclusions without a surrounding halo (Figure 7)^21,40; (2) anisonucleosis, hyperchromasia, and chromatin clumping of infected cells^21,40; (3) areas of tubular damage showing interstitial mononuclear or polymorphonuclear cell infiltrates (Figure 2)^21,40; (4) tubular injury in the form of tubular cell apoptosis, desquamation, and flattened epithelial lining^21,40; and (5) tubulitis with lymphocyte invasion to the basement membrane of the tubular epithelium. When extensive, it is difficult to differentiate between BKVN and allograft rejection (Figure 2).^21,40

In BKVN, electron microscopy examinations would show the following: (1) viral inclusions with diameter size ranging from 30 to 50 nm and (2) tubular damage, including tubular cell necrosis, prominent lysosomal inclusions, and luminal protein and cellular casts.^40,41,49

Differential diagnosis
BK virus infection can be similar to other types of viral infections (CMV, herpes simplex virus, adenovirus). Therefore, to confirm a diagnosis of BKVN, a blood quantitative PCR showing > 60 to 100 BKV copies plus characteristically pathologic morphology results are needed. Different pathological patterns and associations with BKV infection are shown in Figures 2 to 7.

Urine cytology findings for BK virus infections
Urine examinations may reveal BKV-infected cells. The most characteristic abnormality of infected cells is an enlarged nucleus with a single, large basophilic intranuclear inclusion (Figure 1).^34,42

The presence of characteristic cytopathologic changes in infected cells (which have been called decoy cells due to their similarity to renal carcinoma cells) is strongly suggestive of polyomavirus infections.^43,44 Viral replication in the urine is demonstrated by either decoy cells or BKV urine quantitative PCR.³⁶

Cytological urine abnormalities (decoy cells) are suggestive but not specific, sensitive, or definitive for BKV infection because (1) decoy cells can be present in other renal viral infections (such as CMV or adenovirus42) and (2) decoy cells correlate poorly with biopsy-proven BKVN in renal transplant recipients.⁴⁴ Of note, their absence does not exclude the disease.³⁵

Quantitative polymerase chain reaction
Sustained high viral DNA levels in the plasma of renal transplant recipients who have an appropriate clinical picture can suggest BKVN. In a study of 78 renal transplant patients, the sensitivity and specificity of quantitative PCR analyses in detecting BKV DNA were about 100% and 88%, respectively.⁴⁴ In another study, 9 of 9 transplant recipients with biopsy-proven BKVN had BKV DNA detected in plasma by PCR.⁴⁵ However, such DNA was found in only 2 of 41 transplant recipients without nephropathy and in 0 of 17 nontransplant patients with advanced human immunodeficiency virus-1 infection. Viral DNA disappeared with decreased immunosuppression.

Renal transplant recipients can be monitored with quantitative or real-time PCR for BKV infections in either the plasma or urine.^46,47 Multiple retrospective and prospective studies have agreed that viruria precede viremia by 4 weeks.^46-48 Viral replication in the urine as detected by either analysis of urine cytology or demonstration of the virus by quantitative PCR has been shown to be present in 20% to 60% of renal transplant recipients, depending on the method of detection.³⁶ During the first 6 months, 10% to 30% of renal transplant recipients may show levels of BKV viremia; however, BKV viremia can decrease later to 5% to 10% of renal transplant recipients. One study showed that 2% to 10% of renal transplant recipients had no BKVN 12 weeks after BKV viruria.³⁶ Patients with a higher viruria level are highly prone to developing BKV viremia, and patients with high sustained viremia are susceptible to BKVN. In another study, although the risks of viremia and sustained viremia were 3- and 13-fold higher if the urine DNA level was > 9.5 log10 copies/mL, the sensitivity, specificity, positive predictive value, and negative predictive values of urine levels were 70%, 70%, 53%, and 83% for any viremia and 91%, 66%, 33%, and 98% for sustained viremia, respectively.⁶ In addition, a strong correlation was shown between the negativity of urine BKV PCR and blood BKV PCR.50 BK virus DNA levels can alter weekly by 1 to 2 log-folds depending on the commercially available PCR assay. It is recommended that medical decisions, especially those with regard to alterations of immunosup­pression, be made on the basis of trends in quantitative DNA levels rather than on a single measurement.²⁰

Serology
It is not helpful to examine serum for anti-BKV antibodies for a definitive diagnosis of BKV infection because positivity for these antibodies is quite common in the general population.^9,51 During BKV infection, there are high levels of BKV (immunoglobulin G [IgG]) titers during the first 6 weeks of infection or 2 years after primary infection.^51,52 The risk of developing higher levels of BKV IgG is directly correlated with donor anti-BKV antibody positivity.⁵² Anti-BKV antibody does not seem to be protective; therefore, it can increase in both primary infections and reactivation of infections.³⁰ Previous BKV seropos-itivity in the recipient can affect progression of BKV infection, especially progression from viruria to viremia, which is considered a harbinger of BKVN.⁵³ In the laboratory, the intensity of infection can be classified according to the type of antibody response: IgG, IgM, or IgA.⁵³ The utility of assessing anti-BKV antibody levels before and after transplant is not clear. The utility of conducting BKV serology examinations before and after transplant is controversial because it is not entirely clear which antibodies are neutralizing.^54,55 The risk of developing a clinically significant BKV infection is high when transplant is performed between a positive BKV donor and a negative recipient.

Viral culture
Viral culture is rarely used as a method for BKV infection detection outside the research setting. Viral isolation from the clinical specimen can take weeks to months; therefore, this method is not clinically applicable.⁵⁶

Urine electron microscopy
Urine examinations using negative-staining electron microscopy for patients with BKV infection will show cast-like 3-dimensional polyomavirus aggregates, which are called Haufen (Figure 8).⁵⁷ In a retrospective single-center study, Haufen presence was shown to be associated with 100% sensitivity and 99% specificity for biopsy-verified BKVN in kidney transplant recipients.⁵⁷ In addition, a relationship was reported among Haufen, high-level BKV viremia (median copy 1 206 325 copies/mL), and the occurrence of acute kidney injury and BKVN. However, urine analyses in patients with a low viremia (median of 26 959 copies/mL) did not show Haufen bodies. Thus, urinary Haufen bodies can act as a noninvasive method for BKVN diagnosis in renal transplant recipients. This diagnostic technique is of a great utility, especially in differentiating between BKVN and asymptomatic BKV infection. However, it remains to be determined whether this method can be used for diagnosis as it depends on a sophisticated analysis and it also requires a meticulous interpretation by pathologists. In addition, the study did not determine whether urine electron microscopy can discriminate between rejection and BKVN.⁵⁷ Despite these limitations, the presence of a high load of Haufen with equivocal biopsy would highly support the possibility of BKVN rather than rejection as a cause of allograft dysfunction, which could support medical decisions of reduction of immunosuppression rather than augmentation as in cases of rejection.

Therapeutic Interventions
Few controlled studies are available to guide us through the management of BKV infection in renal transplantation.⁵⁸ Currently, there are no available antiviral medications against BKV. However, potential anti-BKV agents have been suggested by several reports. Concomitant administration of these agents with immunosuppression reduction was only documented in uncontrolled retrospective obser­vational studies; therefore, it is difficult to make firm conclusions about their therapeutic efficacy. The usual approach in the management of BKV viremia or BKVN in renal transplant recipients is the reduction of immunosuppression and continuous monitoring of BKV viremia levels using quantitative PCR.^9,59 Various therapeutic interventions are discussed in the following sections.

Immunosuppression reduction
Despite the fact that reduction of immunosup­pression has been the cornerstone in the mana­gement of BKV infection, it also carries a higher risk of rejection, making this decision challenging. Histologically, there is a similar feature between rejection and BKVN, which often shows severe interstitial inflammation in addition to the presence of viral inclusions and SV40 immunohistochemistry may become negative.⁶⁰ Moreover, modification of immunosuppression to treat BKV infection carries a higher incidence of long-term chronic rejection. One study suggested that patients with persistent sustained BKV viremia are prone to the development of de novo donor-specific anti-HLA antibodies.

Cidofovir
Multiple single-center studies and case series have described the benefits of adding cidofovir with immunosuppression reduction. However, no ran­domized controlled trials are available to support this approach.^61,62 One of the limitations of this approach is nephrotoxicity, thus making the decision to use cidofovir unlikely.

Brincidofovir (CMX001)
Because of the nephrotoxicity with cidofovir, scientists had developed brincidofovir, which is a prodrug of cidofovir that is administered orally. Phase 3 clinical trials have shown a lower incidence of nephrotoxicity with brincidofovir.63 Successful outcomes in renal and hematopoietic transplant have been described in multiple case reports after treatment of BKVN with brincidofovir.^64,65 However, larger-scale clinical trials are needed to establish the safety and efficacy of brincidofovir in the management of BKVN patients.

Leflunomide
Leflunomide is an immunosuppressant agent that also has antiviral properties against BKV in vitro.⁶⁶ Several case series have utilized it as a replacement agent in lieu of mycophenolate.^67,68 These studies have shown a significant association between leflunomide and decrease in BKV viral load; however, this does not reflect the cause of BKV viral load (that is, whether it is a result of immunosup­pression reduction or due to the antiviral properties of leflunomide). Side effects of leflunomide include thrombotic microangiopathy, hepatitis, and bone marrow suppression.⁶⁷ The active metabolite of leflunomide (known as teriflunomide or A771726) can be measured, which can be helpful in continuous monitoring of the level of leflunomide and avoid toxicity.⁶⁸ In a case series, achieving a level of 50 to 100 g/mL of teriflunomide or A771726 was associated with a reduction of BKV viral load, as shown in a follow-up of 22 renal transplant patients.⁶⁹ Further prospective controlled studies of leflunomide are needed to confirm the efficacy and safety of this drug against BKV infection⁷⁰

Intravenous immunoglobulin
Intravenous immunoglobulin (IVIG) contains neu­tralizing antibodies against BKV, which makes it a good choice in the management of BKVN.⁷¹ The evidence of using IVIG as adjunctive therapy for BKVN has been described in multiple case reports and case series^72,73; however, no controlled studies have been reported. In patients with hypogam­maglobulinemia, IVIG therapy was beneficial with regard to anti-BKV immunity; the immunomod­ulatory effects of IVIG may guard against allograft rejection in the context of reduced immunosuppression.⁷⁴

Fluoroquinolone
In vitro studies have shown that fluoroquinolone antibiotics can inhibit replication of BKV or SV40 polyomavirus replication in vitro; therefore, fluoroquinolone antibiotics have been considered as potential agents for controlling BKV infection in renal transplant recipients.^75,76 In vitro studies have revealed that fluoroquinolones appear to have an inhibitory effect through reduction of large T antigen expression and inhibition of large T antigen helicase activity.^75,76 In a retrospective study of fluoroquinolone given as prophylaxis against BKV infection in renal transplant recipients, fewer renal transplant recipients who received the fluoroquinolone devel­oped BKV viremia, supporting the probability that fluoroquinolone may have a role in preventing BKV replication.^77,78 A single-center nonrandomized study demonstrated that coadministration of ciprofloxacin and leflunomide were successful in controlling BKV infections.⁷⁹ However, other prospective randomized trials showed no benefit from levofloxacin in renal transplant recipients to control BKV infection.^80-82 Overall, these data suggest that fluoroquinolones do not currently have a clinically significant role in the management of BKV-related diseases.⁸²

Role of cellular immunotherapy in the management of BKV infection
BK virus infections usually occur during childhood; BKV then becomes dormant until it is reactivated after immunosuppression treatment as a result of failure of BKV-reactive T cells to control viral replication.⁸³ Therefore, the idea of this approach depends on the transfer of primed BKV-reactive T cells, which may help in controlling the BKV-associated disease. In the early 1990s, Riddell and associates were the first team to start cellular therapy using T cells to restore antiviral immunity in immunocompromised patients.⁸⁴ Since then, various research teams have refined new approaches for treating various chronic virus-associated diseases using the adoptive T-cell therapy approach.^85,86 Identifying viral immunogenic antigens is necessary for successful generation of virus-specific T cells. Herpesviruses immunodominant epitopes have been defined as researchers successfully used synthetic viral peptides or overlapping peptide pools to produce CMV- or Epstein-Barr-specific T cells.⁸⁷ Newer advanced techniques have been developed using interferon-capture technology or major histocompatibility complex multimers^88,89 to allow rapid selection and virus-specific T-cell enrichment.⁹⁰ Research on treating BKV-associated diseases using immunotherapeutic approaches is still in the early stages, and data on immunodominant BKV epitopes for T-cell priming are limited. Blyth and associates recently reported the use of overlapping peptide pools derived from all 5 BKV antigens to expand BKV-specific human T cells.⁹¹ Functional characterization of the expanded T-cell population confirmed BKV reactivity, cytokine production, and in vitro cytotoxicity.⁹¹ In a pilot study published in 2014, in vitro expansion of virus-reactive T cells was performed by use of overlapping peptide pools that included antigens from Epstein-Barr virus, CMV, adenovirus, BKV, and human herpesvirus 6.⁹² Generated cell products using this protocol were given to patients after hematopoietic stem cell transplant either prophylactically or in response to single or multiple viral infections. Few participants had active BKV infection, which improved after adoptive T-cell transfer.⁹² This study has paved the way to the possibility of management of BKV infection using the adoptive transfer of BKV-reactive T cells.

Conclusions

BK virus is a member of human polyomaviruses, which are DNA viruses; BKV infections lead to tubulointerstitial nephritis and ureteral stenosis in the renal transplant population. The average incidence is about 10% of the renal transplant population.

There is a direct correlation between the incidence of BKV infection and the degree of immunosup­pression, but not the drug itself. Other risk factors include diabetes mellitus, elderly patients, male patients, delayed graft function, acute rejection episodes, and previous CMV infections.

Clinical manifestations of BKV infection range from being asymptomatic to frank nephropathy with disturbed renal function and progressive increase of serum creatinine levels. Urine analysis may show hematuria, pyuria, and cellular casts. Urine microscopy shows decoy cells that are BKV-infected cells. A definitive diagnosis of BKVN is made by renal allograft biopsy using immunohistochemistry, which cross-react with the BKV, specifically SV40 large-T antigen part of the virus. BK virus nephropathy could be missed in about one-third of patients; therefore, 2 core biopsies are needed for confirmation, preferably including the medulla. Renal transplant recipients are usually monitored by serum and urine quantitative PCR for BKV DNA. Viral replication goes through stages, with viruria preceding viremia by about 4 weeks and nephropathy by 12 weeks.

Acute rejection is the main differential diagnosis of BKVN. BK virus nephropathy could be differentiated with BKV inclusions and immunohistologic analyses. In addition, it is important to correlate histologic findings with PCR evidence of viremia.

There are no available antiviral medications for BKV infections, and there are few controlled studies available on management of BKV infection in renal transplant recipients. The concomitant admin­istration of these agents with immunosuppression reduction has been reported in only uncontrolled retrospective observational studies; therefore, it is difficult to make firm conclusions about their therapeutic efficacy. The common approach for BKV infection management is active screening every 3 months after renal transplant; with any levels of BKV viremia, immunosuppression should be reduced and there should be continuous follow-up of BKV viremia levels using quantitative PCR and renal function tests. Newer options, including cellular immunotherapy, may carry potential hope for treatment of BKV infection.

References:

1. Imperiale MJ. The human polyomaviruses: an overview. In: Khalili K, Stoner GL, eds. Human Polyomaviruses: Wiley; 2001:53-71.
   CrossRef - PubMed
   
2. Beimler J, Sommerer C, Zeier M. The influence of immunosuppression on the development of BK virus nephropathy-- does it matter? Nephrol Dial Transplant. 2007;22 Suppl 8:viii66-viii71. doi:10.1093/ndt/gfm646
   CrossRef - PubMed
   
3. Elfadawy N, Flechner SM, Schold JD, et al. Transient versus persistent BK viremia and long-term outcomes after kidney and kidney-pancreas transplantation. Clin J Am Soc Nephrol. 2014;9(3):553-561. doi:10.2215/CJN.08420813
   CrossRef - PubMed
   
4. Karuthu S, Blumberg EA. Common infections in kidney transplant recipients. Clin J Am Soc Nephrol. 2012;7(12):2058-2070. doi:10.2215/CJN.04410512
   CrossRef - PubMed
   
5. Dall A, Hariharan S. BK virus nephritis after renal transplantation. Clin J Am Soc Nephrol. 2008;3 Suppl 2:S68-75. doi:10.2215/CJN.02770707
   CrossRef - PubMed
   
6. Brennan DC, Agha I, Bohl DL, et al. Incidence of BK with tacrolimus versus cyclosporine and impact of preemptive immunosuppression reduction. Am J Transplant. 2005;5(3):582-594. doi:10.1111/j.1600-6143.2005.00742.x
   CrossRef - PubMed
   
7. Sood P, Senanayake S, Sujeet K, et al. Management and outcome of BK viremia in renal transplant recipients: a prospective single-center study. Transplantation. 2012;94(8):814-821.doi:10.1097/TP.0b013e31826690c6
   CrossRef - PubMed
   
8. Hardinger KL, Koch MJ, Bohl DJ, Storch GA, Brennan DC. BK-virus and the impact of pre-emptive immunosuppression reduction: 5-year results. Am J Transplant. 2010;10(2):407-415. doi:10.1111/j.1600-6143.2009.02952.x
   CrossRef - PubMed
   
9. Schaub S, Hirsch HH, Dickenmann M, et al. Reducing immunosuppression preserves allograft function in presumptive and definitive polyomavirus-associated nephropathy. Am J Transplant. 2010;10(12):2615-2623. doi:10.1111/j.1600-6143.2010.03310.x
   CrossRef - PubMed
   
10. Seifert ME, Gunasekaran M, Horwedel TA, et al. Polyomavirus reactivation and immune responses to kidney-specific self-antigens in transplantation. J Am Soc Nephrol. 2017;28(4):1314-1325. doi:10.1681/ASN.2016030285
    CrossRef - PubMed
    
11. Baksh FK, Finkelstein SD, Swalsky PA, Stoner GL, Ryschkewitsch CF, Randhawa P. Molecular genotyping of BK and JC viruses in human polyomavirus-associated interstitial nephritis after renal transplantation. Am J Kidney Dis. 2001;38(2):354-365. doi:10.1053/ajkd.2001.26101
    CrossRef - PubMed
    
12. Garces JC. BK virus-associated nephropathy in kidney transplant recipients. Ochsner J. 2010;10(4):245-249.
    CrossRef - PubMed
    
13. Dalianis T, Hirsch HH. Human polyomaviruses in disease and cancer. Virology. 2013;437(2):63-72.doi:10.1016/j.virol.2012.12.015
    CrossRef - PubMed
    
14. Goudsmit J, Wertheim-van Dillen P, van Strien A, van der Noordaa J. The role of BK virus in acute respiratory tract disease and the presence of BKV DNA in tonsils. J Med Virol. 1982;10(2):91-99. doi:10.1002/jmv.1890100203
    CrossRef - PubMed
    
15. Vanchiere JA, Abudayyeh S, Copeland CM, Lu LB, Graham DY, Butel JS. Polyomavirus shedding in the stool of healthy adults. J Clin Microbiol. 2009;47(8):2388-2391. doi:10.1128/JCM.02472-08
    CrossRef - PubMed
    
16. Boldorini R, Allegrini S, Miglio U, et al. Serological evidence of vertical transmission of JC and BK polyomaviruses in humans. J Gen Virol. 2011;92(Pt 5):1044-1050. doi:10.1099/vir.0.028571-0
    CrossRef - PubMed
    
17. Boldorini R, Allegrini S, Miglio U, et al. BK virus sequences in specimens from aborted fetuses. J Med Virol. 2010;82(12):2127-2132. doi:10.1002/jmv.21923
    CrossRef - PubMed
    
18. Pahari A, Rees L. BK virus-associated renal problems--clinical implications. Pediatr Nephrol. 2003;18(8):743-748. doi:10.1007/s00467-003-1184-3
    CrossRef - PubMed
    
19. Peinemann F, de Villiers EM, Dorries K, Adams O, Vogeli TA, Burdach S. Clinical course and treatment of haemorrhagic cystitis associated with BK type of human polyomavirus in nine paediatric recipients of allogeneic bone marrow transplants. Eur J Pediatr. 2000;159(3):182-188. doi:10.1007/s004310050047
    CrossRef - PubMed
    
20. Bressollette-Bodin C, Coste-Burel M, Hourmant M, Sebille V, Andre-Garnier E, Imbert-Marcille BM. A prospective longitudinal study of BK virus infection in 104 renal transplant recipients. Am J Transplant. 2005;5(8):1926-1933. doi:10.1111/j.1600-6143.2005.00934.x
    CrossRef - PubMed
    
21. Howell DN, Smith SR, Butterly DW, et al. Diagnosis and management of BK polyomavirus interstitial nephritis in renal transplant recipients. Transplantation. 1999;68(9):1279-1288. doi:10.1097/00007890-199911150-00011
    CrossRef - PubMed
    
22. Funk GA, Steiger J, Hirsch HH. Rapid dynamics of polyomavirus type BK in renal transplant recipients. J Infect Dis. 2006;193(1):80-87. doi:10.1086/498530
    CrossRef - PubMed
    
23. Schold JD, Rehman S, Kayle LK, Magliocca J, Srinivas TR, Meier-Kriesche HU. Treatment for BK virus: incidence, risk factors and outcomes for kidney transplant recipients in the United States. Transpl Int. 2009;22(6):626-634. doi:10.1111/j.1432-2277.2009.00842.x
    CrossRef - PubMed
    
24. Gralla J, Huskey J, Wiseman AC. Trends in immune function assay (ImmuKnow; Cylex) results in the first year post-transplant and relationship to BK virus infection. Nephrol Dial Transplant. 2012;27(6):2565-2570. doi:10.1093/ndt/gfr675
    CrossRef - PubMed
    
25. Fink JC, Wiland AM, Rochussen JR, Drachenberg CB, Papadimitriou JP. Increased incidence Of BK polyoma virus in renal transplant recipients treated with Prograf (Abstract 1051). Transplant J. 2000;69(8):S385.
    CrossRef - PubMed
    
26. Dadhania D, Snopkowski C, Ding R, et al. Epidemiology of BK virus in renal allograft recipients: independent risk factors for BK virus replication. Transplantation. 2008;86(4):521-528. doi:10.1097/TP.0b013e31817c6447
    CrossRef - PubMed
    
27. Lipshutz GS, Flechner SM, Govani MV, Vincenti F. BK nephropathy in kidney transplant recipients treated with a calcineurin inhibitor-free immunosuppression regimen. Am J Transplant. 2004;4(12):2132-2134. doi:10.1046/j.1600-6143.2004.00600.x
    CrossRef - PubMed
    
28. Sachdeva MS, Nada R, Jha V, Sakhuja V, Joshi K. The high incidence of BK polyoma virus infection among renal transplant recipients in India. Transplantation. 2004;77(3):429-431. doi:10.1097/01.TP.0000113163.02039.30
    CrossRef - PubMed
    
29. Hirsch HH, Yakhontova K, Lu M, Manzetti J. BK Polyomavirus replication in renal tubular epithelial cells is inhibited by sirolimus, but activated by tacrolimus through a pathway involving FKBP-12. Am J Transplant. 2016;16(3):821-832. doi:10.1111/ajt.13541
    CrossRef - PubMed
    
30. Bohl DL, Storch GA, Ryschkewitsch C, et al. Donor origin of BK virus in renal transplantation and role of HLA C7 in susceptibility to sustained BK viremia. Am J Transplant. 2005;5(9):2213-2221. doi:10.1111/j.1600-6143.2005.01000.x
    CrossRef - PubMed
    
31. Thomas A, Dropulic LK, Rahman MH, Geetha D. Ureteral stents: a novel risk factor for polyomavirus nephropathy. Transplantation. 2007;84(3):433-436. doi:10.1097/01.tp.0000269616.21698.10
    CrossRef - PubMed
    
32. Sharif A, Alachkar N, Bagnasco S, et al. Incidence and outcomes of BK virus allograft nephropathy among ABO- and HLA-incompatible kidney transplant recipients. Clin J Am Soc Nephrol. 2012;7(8):1320-1327. doi:10.2215/CJN.00770112
    CrossRef - PubMed
    
33. Awadalla Y, Randhawa P, Ruppert K, Zeevi A, Duquesnoy RJ. HLA mismatching increases the risk of BK virus nephropathy in renal transplant recipients. Am J Transplant. 2004;4(10):1691-1696. doi:10.1111/j.1600-6143.2004.00563.x
    CrossRef - PubMed
    
34. Kahan AV, Coleman DV, Koss LG. Activation of human polyomavirus infection-detection by cytologic technics. Am J Clin Pathol. 1980;74(3):326-332. doi:10.1093/ajcp/74.3.326
    CrossRef - PubMed
    
35. Randhawa P, Ramos EJ. BK viral nephropathy: an overview. Transplant Rev. 2007;21(2):77-85.
    CrossRef - PubMed
    
36. Hirsch HH, Brennan DC, Drachenberg CB, et al. Polyomavirus-associated nephropathy in renal transplantation: interdisciplinary analyses and recommendations. Transplantation. 2005;79(10):1277-1286. doi:10.1097/01.tp.0000156165.83160.09
    CrossRef - PubMed
    
37. Wiseman AC. Polyomavirus nephropathy: a current perspective and clinical considerations. Am J Kidney Dis. 2009;54(1):131-142. doi:10.1053/j.ajkd.2009.01.271
    CrossRef - PubMed
    
38. Drachenberg CB, Papadimitriou JC. Polyomavirus-associated nephropathy: update in diagnosis. Transpl Infect Dis. 2006;8(2):68-75. doi:10.1111/j.1399-3062.2006.00154.x
    CrossRef - PubMed
    
39. Drachenberg CB, Papadimitriou JC, Hirsch HH, et al. Histological patterns of polyomavirus nephropathy: correlation with graft outcome and viral load. Am J Transplant. 2004;4(12):2082-2092. doi:10.1046/j.1600-6143.2004.00603.x
    CrossRef - PubMed
    
40. Nickeleit V, Hirsch HH, Zeiler M, et al. BK-virus nephropathy in renal transplants-tubular necrosis, MHC-class II expression and rejection in a puzzling game. Nephrol Dial Transplant. 2000;15(3):324-332.doi:10.1093/ndt/15.3.324
    CrossRef - PubMed
    
41. Randhawa PS, Finkelstein S, Scantlebury V, et al. Human polyoma virus-associated interstitial nephritis in the allograft kidney. Transplantation. 1999;67(1):103-109. doi:10.1097/00007890-199901150-00018
    CrossRef - PubMed
    
42. Traystman MD, Gupta PK, Shah KV, et al. Identification of viruses in the urine of renal transplant recipients by cytomorphology. Acta Cytol. 1980;24(6):501-510.
    CrossRef - PubMed
    
43. Ramos E, Drachenberg CB, Papadimitriou JC, et al. Clinical course of polyoma virus nephropathy in 67 renal transplant patients. J Am Soc Nephrol. 2002;13(8):2145-2151. doi:10.1097/01.asn.0000023435.07320.81
    CrossRef - PubMed
    
44. Hirsch HH, Knowles W, Dickenmann M, et al. Prospective study of polyomavirus type BK replication and nephropathy in renal-transplant recipients. N Engl J Med. 2002;347(7):488-496. doi:10.1056/NEJMoa020439
    CrossRef - PubMed
    
45. Drachenberg CB, Beskow CO, Cangro CB, et al. Human polyoma virus in renal allograft biopsies: morphological findings and correlation with urine cytology. Hum Pathol. 1999;30(8):970-977. doi:10.1016/s0046-8177(99)90252-6
    CrossRef - PubMed
    
46. Coleman DV, Gardner SD, Field AM. Human polyomavirus infection in renal allograft recipients. Br Med J. 1973;3(5876):371-375. doi:10.1136/bmj.3.5876.371
    CrossRef - PubMed
    
47. Agha I, Alvarez A, Lopez L, Hardinger KL, Torrence S, Miller BJ. Human polyoma virus infects a high proportion of renal allograft recipients and the incidence is not affected by choice of calcineurin inhibitor. J Am Soc Nephrol. 2001;12:847A.
    CrossRef - PubMed
    
48. Saundh BK, Baker R, Harris M, Welberry Smith MP, Cherukuri A, Hale A. Early BK polyomavirus (BKV) reactivation in donor kidney is a risk factor for development of BKV-associated nephropathy. J Infect Dis. 2013;207(1):137-141. doi:10.1093/infdis/jis642
    CrossRef - PubMed
    
49. Bardak S, Turgutalp K, Ballı E, et al. BK virus nephropathy in a renal transplant patient: Potential role of electron microscopy in diagnosis. Nefrologia. 2016;36(5):565-567. doi:10.1016/j.nefro.2016.03.015
    CrossRef - PubMed
    
50. Randhawa PS, Demetris AJ. Nephropathy due to polyomavirus type BK. N Engl J Med. 2000;342(18):1361-1363. doi:10.1056/NEJM200005043421809
    CrossRef - PubMed
    
51. Gardner SD, MacKenzie EF, Smith C, Porter AA. Prospective study of the human polyomaviruses BK and JC and cytomegalovirus in renal transplant recipients. J Clin Pathol. 1984;37(5):578-586. doi:10.1136/jcp.37.5.578
    CrossRef - PubMed
    
52. Shah KV. Human polyomavirus BKV and renal disease. Nephrol Dial Transplant. 2000;15(6):754-755. doi:10.1093/ndt/15.6.754
    CrossRef - PubMed
    
53. Randhawa P, Bohl D, Brennan D, et al. Longitudinal analysis of levels of immunoglobulins against BK virus capsid proteins in kidney transplant recipients. Clin Vaccine Immunol. 2008;15(10):1564-1571. doi:10.1128/CVI.00206-08
    CrossRef - PubMed
    
54. Smith JM, McDonald RA, Finn LS, Healey PJ, Davis CL, Limaye AP. Polyomavirus nephropathy in pediatric kidney transplant recipients. Am J Transplant. 2004;4(12):2109-2117. doi:10.1111/j.1600-6143.2004.00629.x
    CrossRef - PubMed
    
55. Ginevri F, De Santis R, Comoli P, et al. Polyomavirus BK infection in pediatric kidney-allograft recipients: a single-center analysis of incidence, risk factors, and novel therapeutic approaches. Transplantation. 2003;75(8):1266-1270. doi:10.1097/01.TP.0000061767.32870.72
    CrossRef - PubMed
56. Arthur RR, Shah KV. Occurrence and significance of papovaviruses BK and JC in the urine. Prog Med Virol. 1989;36:42-61.
    CrossRef - PubMed
    
57. Singh HK, Andreoni KA, Madden V, et al. Presence of urinary Haufen accurately predicts polyomavirus nephropathy. J Am Soc Nephrol. 2009;20(2):416-427. doi:10.1681/ASN.2008010117
    CrossRef - PubMed
    
58. Johnston O, Jaswal D, Gill JS, Doucette S, Fergusson DA, Knoll GA. Treatment of polyomavirus infection in kidney transplant recipients: a systematic review. Transplantation. 2010;89(9):1057-1070. doi:10.1097/TP.0b013e3181d0e15e
    CrossRef - PubMed
    
59. Weiss AS, Gralla J, Chan L, Klem P, Wiseman AC. Aggressive immunosuppression minimization reduces graft loss following diagnosis of BK virus-associated nephropathy: a comparison of two reduction strategies. Clin J Am Soc Nephrol. 2008;3(6):1812-1819. doi:10.2215/CJN.05691207
    CrossRef - PubMed
    
60. Menter T, Mayr M, Schaub S, Mihatsch MJ, Hirsch HH, Hopfer H. Pathology of resolving polyomavirus-associated nephropathy. Am J Transplant. 2013;13(6):1474-1483. doi:10.1111/ajt.12218
    CrossRef - PubMed
    
61. Kuypers DR, Vandooren AK, Lerut E, et al. Adjuvant low-dose cidofovir therapy for BK polyomavirus interstitial nephritis in renal transplant recipients. Am J Transplant. 2005;5(8):1997-2004. doi:10.1111/j.1600-6143.2005.00980.x
    CrossRef - PubMed
    
62. Savona MR, Newton D, Frame D, Levine JE, Mineishi S, Kaul DR. Low-dose cidofovir treatment of BK virus-associated hemorrhagic cystitis in recipients of hematopoietic stem cell transplant. Bone Marrow Transplant. 2007;39(12):783-787. doi:10.1038/sj.bmt.1705678
    CrossRef - PubMed
    
63. Marty FM, Winston DJ, Rowley SD, et al. CMX001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369(13):1227-1236. doi:10.1056/NEJMoa1303688
    CrossRef - PubMed
    
64. Reisman L, Habib S, McClure GB, Latiolais LS, Vanchiere JA. Treatment of BK virus-associated nephropathy with CMX001 after kidney transplantation in a young child. Pediatr Transplant. 2014;18(7):E227-231.doi:10.1111/petr.12340
    CrossRef - PubMed
    
65. Papanicolaou GA, Lee YJ, Young JW, et al. Brincidofovir for polyomavirus-associated nephropathy after allogeneic hematopoietic stem cell transplantation. Am J Kidney Dis. 2015;65(5):780-784. doi:10.1053/j.ajkd.2014.11.020
    CrossRef - PubMed
    
66. Liacini A, Seamone ME, Muruve DA, Tibbles LA. Anti-BK virus mechanisms of sirolimus and leflunomide alone and in combination: toward a new therapy for BK virus infection. Transplantation. 2010;90(12):1450-1457. doi:10.1097/TP.0b013e3182007be2
    CrossRef - PubMed
    
67. Williams JW, Javaid B, Kadambi PV, et al. Leflunomide for polyomavirus type BK nephropathy. N Engl J Med. 2005;352(11):1157-1158. doi:10.1056/NEJM200503173521125
    CrossRef - PubMed
    
68. Krisl JC, Taber DJ, Pilch N, et al. Leflunomide efficacy and pharmacodynamics for the treatment of BK viral infection. Clin J Am Soc Nephrol. 2012;7(6):1003-1009. doi:10.2215/CJN.12531211
    CrossRef - PubMed
    
69. Josephson MA, Gillen D, Javaid B, et al. Treatment of renal allograft polyoma BK virus infection with leflunomide. Transplantation. 2006;81(5):704-710. doi:10.1097/01.tp.0000181149.76113.50
    CrossRef - PubMed
    
70. Cuellar-Rodriguez J, Stephany B, Poggio E, et al. Contrasting patterns of viral load response in transplant recipients with BK polyomavirus DNAemia on leflunomide therapy. Clin Transplant. 2013;27(3):E230-236. doi:10.1111/ctr.12110
    CrossRef - PubMed
    
71. Randhawa P, Pastrana DV, Zeng G, et al. Commercially available immunoglobulins contain virus neutralizing antibodies against all major genotypes of polyomavirus BK. Am J Transplant. 2015;15(4):1014-1020. doi:10.1111/ajt.13083
    CrossRef - PubMed
    
72. Vu D, Shah T, Ansari J, Naraghi R, Min D. Efficacy of intravenous immunoglobulin in the treatment of persistent BK viremia and BK virus nephropathy in renal transplant recipients. Transplant Proc. 2015;47(2):394-398. doi:10.1016/j.transproceed.2015.01.012
    CrossRef - PubMed
    
73. Randhawa PS, Schonder K, Shapiro R, Farasati N, Huang Y. Polyomavirus BK neutralizing activity in human immunoglobulin preparations. Transplantation. 2010;89(12):1462-1465. doi:10.1097/tp.0b013e3181daaaf1
    CrossRef - PubMed
    
74. Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012;367(21):2015-2025. doi:10.1056/NEJMra1009433
    CrossRef - PubMed
    
75. Sharma BN, Li R, Bernhoff E, Gutteberg TJ, Rinaldo CH. Fluoroquinolones inhibit human polyomavirus BK (BKV) replication in primary human kidney cells. Antiviral Res. 2011;92(1):115-123. doi:10.1016/j.antiviral.2011.07.012
    CrossRef - PubMed
    
76. Portolani M, Pietrosemoli P, Cermelli C, et al. Suppression of BK virus replication and cytopathic effect by inhibitors of prokaryotic DNA gyrase. Antiviral Res. 1988;9(3):205-218. doi:10.1016/0166-3542(88)90004-6
    CrossRef - PubMed
    
77. Wojciechowski D, Chanda R, Chandran S, et al. Ciprofloxacin prophylaxis in kidney transplant recipients reduces BK virus infection at 3 months but not at 1 year. Transplantation. 2012;94(11):1117-1123. doi:10.1097/TP.0b013e31826ec74e
    CrossRef - PubMed
    
78. Gabardi S, Waikar SS, Martin S, et al. Evaluation of fluoroquinolones for the prevention of BK viremia after renal transplantation. Clin J Am Soc Nephrol. 2010;5(7):1298-1304. doi:10.2215/CJN.08261109
    CrossRef - PubMed
79. Zaman RA, Ettenger RB, Cheam H, Malekzadeh MH, Tsai EW. A novel treatment regimen for BK viremia. Transplantation. 2014;97(11):1166-1171. doi:10.1097/01.TP.0000441825.72639.4f
    CrossRef - PubMed
    
80. Lee BT, Gabardi S, Grafals M, et al. Efficacy of levofloxacin in the treatment of BK viremia: a multicenter, double-blinded, randomized, placebo-controlled trial. Clin J Am Soc Nephrol. 2014;9(3):583-589. doi:10.2215/CJN.04230413
    CrossRef - PubMed
    
81. Knoll GA, Humar A, Fergusson D, et al. Levofloxacin for BK virus prophylaxis following kidney transplantation: a randomized clinical trial. JAMA. 2014;312(20):2106-2114. doi:10.1001/jama.2014.14721
    CrossRef - PubMed
    
82. Hirsch HH, Randhawa P, Practice ASTIDCo. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013;13 Suppl 4:179-188. doi:10.1111/ajt.12110
    CrossRef - PubMed
    
83. Wright AJ, Gill JS. Strategies to prevent BK virus infection in kidney transplant recipients. Curr Opin Infect Dis. 2016;29(4):353-358. doi:10.1097/QCO.0000000000000278
    CrossRef - PubMed
    
84. Riddell SR, Watanabe KS, Goodrich JM, Li CR, Agha ME, Greenberg PD. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science. 1992;257(5067):238-241. doi:10.1126/science.1352912
    CrossRef - PubMed
    
85. Icheva V, Kayser S, Wolff D, et al. Adoptive transfer of Epstein-Barr virus (EBV) nuclear antigen 1-specific t cells as treatment for EBV reactivation and lymphoproliferative disorders after allogeneic stem-cell transplantation. J Clin Oncol. 2013;31(1):39-48. doi:10.1200/JCO.2011.39.8495
    CrossRef - PubMed
    
86. Crough T, Beagley L, Smith C, Jones L, Walker DG, Khanna R. Ex vivo functional analysis, expansion and adoptive transfer of cytomegalovirus-specific T-cells in patients with glioblastoma multiforme. Immunol Cell Biol. 2012;90(9):872-880. doi:10.1038/icb.2012.19
    CrossRef - PubMed
    
87. Khanna R, Smith C. Cellular immune therapy for viral infections in transplant patients. Indian J Med Res. 2013;138(5):796-807.
    CrossRef - PubMed
    
88. Moosmann A, Bigalke I, Tischer J, et al. Effective and long-term control of EBV PTLD after transfer of peptide-selected T cells. Blood. 2010;115(14):2960-2970.doi:10.1182/blood-2009-08-236356
    CrossRef - PubMed
    
89. Schmitt A, Tonn T, Busch DH, et al. Adoptive transfer and selective reconstitution of streptamer-selected cytomegalovirus-specific CD8+ T cells leads to virus clearance in patients after allogeneic peripheral blood stem cell transplantation. Transfusion. 2011;51(3):591-599. doi:10.1111/j.1537-2995.2010.02940.x
    CrossRef - PubMed
    
90. Feuchtinger T, Opherk K, Bethge WA, et al. Adoptive transfer of pp65-specific T cells for the treatment of chemorefractory cytomegalovirus disease or reactivation after haploidentical and matched unrelated stem cell transplantation. Blood. 2010;116(20):4360-4367. doi:10.1182/blood-2010-01-262089
    CrossRef - PubMed
    
91. Blyth E, Clancy L, Simms R, et al. BK virus-specific T cells for use in cellular therapy show specificity to multiple antigens and polyfunctional cytokine responses. Transplantation. 2011;92(10):1077-1084. doi:10.1097/TP.0b013e31823328c0
    CrossRef - PubMed
    
92. Papadopoulou A, Gerdemann U, Katari UL, et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014;6(242):242ra283. doi:10.1126/scitranslmed.3008825
    CrossRef - PubMed
    
93. Nickeleit V, Mihatsch MJ. Polyomavirus nephropathy in native kidneys and renal allografts: an update on an escalating threat. Transpl Int. 2006;19(12):960-973. doi:10.1111/j.1432-2277.2006.00360.x
    CrossRef - PubMed
    
94. Drachenberg RC, Drachenberg CB, Papadimitriou JC, et al. Morphological spectrum of polyoma virus disease in renal allografts: diagnostic accuracy of urine cytology. Am J Transplant. 2001;1(4):373-381.
    CrossRef - PubMed
    
95. Petrogiannis-Haliotis T, Sakoulas G, Kirby J, et al. BK-related polyomavirus vasculopathy in a renal-transplant recipient. N Engl J Med. 2001;345(17):1250-1255. doi:10.1056/NEJMoa010319
    CrossRef - PubMed
    
96. Hirsch HH, Randhawa P; AST Infectious Diseases Community of Practice. BK polyomavirus in solid organ transplantation. Am J Transplant. 2013;13 Suppl 4:179-88. doi:10.1111/ajt.12110
    CrossRef - PubMed