Skip to main content
SpringerLink
Log in

Iron withholding: A defense against viral infections

  • Mini-Review
  • Published:
Biometals Aims and scope Submit manuscript

Abstract

A variety of laboratory and clinical investigations during the past 15 years have observed that one of the dangers of excessive iron is its ability to favor animal viral infections. The metal is essential for host cell synthesis of virions and can also impair defense cell function and increase oxidative stress. In both animal models and humans, viral infections cause upregulation of the iron withholding defense system. Factors that suppress the system enhance viral progression; factors that strengthen the system augment host defense. Procedures designed to reinforce the system are being developed and tested; some of these may become useful adjuncts in prevention and management of viral diseases.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abbud RA, Finegan CK, Guay LA, Rich EA. 1995 Enhanced production of human immunodeficiency virus type I by in vitro infected alveolar macrophages from otherwise healthy cigarette smokers. J Infec Dis 172, 859–863.

    Google Scholar 

  • Arber N, Moshkowitz M, Konikoff F, et al. 1995 Elevated serum iron predicts poor response to interferon treatment in patients with chronic HCV infection. Dig Dis Sci 40, 2431–2433.

    Google Scholar 

  • Bacon BR, Rebholz AE, Fried M, Di Biscegli AM. 1993 Beneficial effect of iron reduction therapy in patients with chronic hepatitis C who failed to respond to interferon-α. Hepatology 18, 150A.

    Google Scholar 

  • Barton A, Cable E, Smith L, Banner B, Bonkovsky H. 1993 Distribution of iron in the liver predicts the response of chronic hepatitis C infection to interferon therapy. Hepatology 18, 150A.

    Google Scholar 

  • Baruchel S, Gao Q, Wainberg MA. 1991 Desferrioxamine and HIV. Lancet 337, 1356.

    Google Scholar 

  • Bharadwaj M, Khanna N, Mathur A, Chaturvedi UC. 1991 Effect of macrophage-derived factor on hypoferraemia induced by Japanese encephalitis virus in mice. Clin Exp Immunol 83, 215–218.

    Google Scholar 

  • Blumberg BS, Lustbader Ed, Whitford PL. 1981 Changes in serum iron levels due to infection with hepatitis B virus. Proc Natl Acad Sci USA 78, 3222–3224.

    Google Scholar 

  • Blumberg BS, Hann H-WL, Mildvan D, Mathur U, Lustbader E, London WT. 1984 Iron and iron binding proteins in persistent generalized lymphadenopathy and AIDS. Lancet i, 347.

    Google Scholar 

  • Boelaert JR, Weinberg GA, Weinberg ED. 1996 Altered iron metabolism in HIV infection: mechanisms, possible consequences, and proposals for management. Infect Agents Dis 5, 35–46

    Google Scholar 

  • Caraceni P, Fagiuoli S, Van Thiel DH. 1994 Iron reduction therapy: simply camoflage, or a real weapon? Am J Gastroenterol 89, 971–973.

    Google Scholar 

  • Cemeroglu AP, Ozsoylu S. 1994 Haematologic consequences of viral infections including serum iron status. Eur J Pediatr 153, 171–173.

    Google Scholar 

  • Cinatl J Jr, Cinatl J, Rabenau H, Gumbel HO, Kornhuber B, Doerr HW. 1994 In vitro inhibition of human cytomegalovirus replication by desferrioxamine. Antiviral Res 25, 73–77.

    Google Scholar 

  • Clarke JR, Taylor IK, Fleming J, Nukuna A, Williamson JD, Mitchell DM. 1993 The epidemiology of HIV-1 infection of the lung in AIDS patients. AIDS 7, 555–560.

    Google Scholar 

  • Costagliola DG, de Montalembert M, Lefrer J-J, et al. 1994 Dose of desferrioxamine and evolution of HIV-1 infection in thalassemic patients. Br J Haematol 87, 849–852.

    Google Scholar 

  • Deugnier Y, Battistelli D, Jouanolle H, et al. 1991 Hepatitis B virus infection markers in genetic haemochromatosis. J. Hepatol 13, 286–290.

    Google Scholar 

  • Di Biscegli AM, Axiotis CA, Hoofnagle JH, Bacon BR. 1991 Measurements of iron status in patients with chronic hepatitis. Gastroenterology 102, 2108–2113.

    Google Scholar 

  • Fargion, S, Piperno A, Cappelini MD. 1992 Hepatitis C virus and porphryia cutanea tarda. Hepatology 16, 1322–1326.

    Google Scholar 

  • Felton C, Lustbader ED, Merten C, Blumberg BS. 1979 Serum iron levels and response to hepatitis B virus. Proc Natl Acad Sci USA 76, 2438–2441.

    Google Scholar 

  • Fischl M, Galfin JE, Levine JD, et al. 1990 Recombinant human erythropoietin for patients with AIDS treated with zidovudine. New Engl J Med 322, 1488–1493.

    Google Scholar 

  • Gangaidzo IT, Gordeuk VR. 1995 Hepatocellular carcinoma and African iron overload. Gut 37, 727–730.

    Google Scholar 

  • Hayashi I, Takikawa T, Nishimura N, Yano M, Isomura T, Sakamoto N. 1994 Improvement of serum amino-transferase levels after phlebotomy in patients with chronic active hepatitis C and excess hepatic iron. Am J Gastroenterol 89, 986–988.

    Google Scholar 

  • Karupiah G, Harris N. 1995 Inhibition of viral replication by nitric oxide and its reversal by ferrous sulfate and tricarboxylic acid metabolites. J Exp Med 181, 2171–2179.

    Google Scholar 

  • Karupiah G, Xie QW, Butler RM, Nathan C, Duarte C, MacMicking JD. 1993 Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science 261, 1445–1448.

    Google Scholar 

  • Lazdins JK, Alteri E, Klimkait T, et al. 1991 Lack of effect of desferrioxamine on in vitro HIV-1 replication. Lancet 338, 1341–1342.

    Google Scholar 

  • Lustbader ED, Hann H-WL, Blumberg BS. 1983 Serum ferritin as a predictor of host response to hepatitis B virus infection. Science 220, 423–425.

    Google Scholar 

  • Mudido P, George SD, Dorazio D, O'Brien WA, Lederman MM. 1994 Blood transfusion may increase HIV expression. Am Soc Microbiol, Interscience Conf Antimicrob Agents Chemother 130A.

  • Newman SL, Gootee L, Brunner G, Deepe GS Jr. 1994 Chloroquine induces human macrophage killing of Histoplasma capsulatum by limiting the availability of intracellular iron and is therapeutic in a murine model of histoplasmosis. J Clin Invest 93, 1422–1429.

    Google Scholar 

  • Nieman RB. Fleming J, Coker RJ, Harris JRW, Mitchell DM. 1993 The effect of cigarette smoking on the development of AIDS in HIV-1-seropositive individuals. AIDS 7, 705–710.

    Google Scholar 

  • Olivares M, Walter T, Llaguno S, Osorio M, Chadud P, Velozo L. 1993 Changes in the hemogram and in the laboratory parameters indicative of iron metabolism in mild viral infections. Sangre-Barc 38, 211–216.

    Google Scholar 

  • Piperno A, D'Alba R, Roffi L, Fargion S, Mancia G, Fiorelli G. 1993 Relation between α-interferon response and liver iron stores in chronic hepatitis C. Hepatology 18, 250A.

  • Sappey C, Boelaert JR, Legrand-Poels S, Forceille C, Favier A, Piette J. 1995 Iron chelation decreases NF-κB and HIV type 1 activation due to oxidative stress. AIDS Res Hum Retroviruses 11, 1049–1061.

    Google Scholar 

  • Schwarz KB, Korba B. 1990 Desferrioxamine inhibits hepatitis B virus virion production by HepG2 cells. Hepatology 12, 972A.

  • Senba M, Nakamura T, Hakura H. 1985 Statistical analysis of relationship between iron accumulation and hepatitis B surface antigen. Am J Clin Pathol 84, 340–342.

    Google Scholar 

  • Sloand E, Kumar P, Klein HG, Merritt S, Sacher R. 1994 Transfusion of blood components to persons infected with human immunodeficiency virus type 1: relationship to opportunistic infection. Transfusion 34, 48–53.

    Google Scholar 

  • Sperber K, Kalb TH, Stecher VJ, Banerjee R, Mayer L. 1993 Inhibition of human immunodeficiency virus type 1 replication by hydroxychloroquine in T cells and monocytes. AIDS Res Hum Retroviruses 9, 91–98.

    Google Scholar 

  • Sperber K, Louie M, Kraus T, Proner J, Sapira E, Lin S, Stecher V, Mayer L. 1995 Hydroxychloroquine treatment of patients with human immunodeficiency virus type 1. Clin Therapeut 17, 622–625.

    Google Scholar 

  • Tabor E, Epstein JS, Hewlett IK, Lee SF. 1991 Inhibition of desferrioxamine of in vitro replication of HIV-1. Lancet 337, 795.

    Google Scholar 

  • Taylor RL Jr, Austic RE, Dietert RR. 1991 Dietary arginine influences Rous sarcoma growth in a major histocompatability complex progressor genotype. Proc Soc Exp Biol Med 199, 38–41.

    Google Scholar 

  • Tsai W-P, Nara PL, Kung H-F, Oroszlan S. 1990 Inhibition of human immunodeficiency virus infectivity by chloroquine. AIDS Res Hum Retroviruses 6, 481–489.

    Google Scholar 

  • Van Thiel DH, Friedlander L, Fagiuoli S, Wright HI, Irish W, Gavaler JS. 1994 Response to interferon-α therapy is influenced by the iron content of the liver. J Hepatol 20, 410–415.

    Google Scholar 

  • Weinberg ED. 1992 Iron depletion: a defense against intracellular infection and neoplasia. Life Sci 50, 1289–1297.

    Google Scholar 

  • Weinberg ED. 1993 Association of iron with respiratory tract neoplasia. J Trace Element Exp Med 6, 117–123.

    Google Scholar 

  • Weinberg ED. 1995 Acquisition of iron and other nutrients in vivo. In Roth JA, Bolin CA, Brogden KA, Minion FC, Wannemuehler MJ, eds. Virulence Mechanisms of Bacterial Pathogens. Washington, DC: American Society for Microbiology: 79–94.

    Google Scholar 

  • Weinberg ED, 1996 The role of iron in cancer. Eur J Cancer Prev 5, 19–36

    Google Scholar 

  • Weinberg ED, Weinberg GA. 1995 The role of iron in infection. Curr Opin Infect Dis 8, 164–169.

    Google Scholar 

  • Weiss G, Werner-Felmayer G, Werner ER, Grunewald K, Wachter H, Hentze MW. 1994 Iron regulates nitric oxide synthase activity by controlling nuclear transcription. J Exp Med 180, 969–976.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biology and Program in Medical Sciences, Indiana University, Bloomington, IN, USA

    E. D. Weinberg

Authors
  1. E. D. Weinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Weinberg, E.D. Iron withholding: A defense against viral infections. Biometals 9, 393–399 (1996). https://doi.org/10.1007/BF00140609

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00140609

Keywords

Search

Navigation