Sequences within the feline immunodeficiency virus long terminal repeat that regulate gene expression and respond to activation by feline herpesvirus type 1

doi:10.1016/0042-6822(92)91235-M

Virology

Volume 190, Issue 1, September 1992, Pages 465-468

https://doi.org/10.1016/0042-6822(92)91235-M Get rights and content

Abstract

We constructed a series of deletion mutants of feline immunodeficiency virus (FIV) long terminal repeat (LTR) to identify the regions that regulate gene expression and are responsive to trans-activation of FIV LTR by feline herpes-virus type 1 (FHV-1). We demonstrated that sequences between −124 and −79, and between −21 and −32 (relative to the cap site) are essential for gene expression of FIV in Felis catus whole fetus 4 (fcwf-4) cells. Further, we demonstrated that the sequence between −63 and −23 responds to trans-activation of FIV LTR by FHV-1 in fcwf-4 cells.

References (41)

B.R. Cullen et al.
Cell
(1989)
Y. Kawaguchi et al.
Virology
(1991)
F.L. Graham et al.
Virology
(1973)
M.K. Jackson et al.
Virology
(1991)
T.W. Hai et al.
Cell
(1988)
M. Horikoshi et al.
Cell
(1988)
B.J. Biegalke et al.
Virology
(1991)
R. Yuan et al.
Virology
(1989)
T. Fujita et al.
Cell
(1987)
R.A. Olmsted et al.

R.A. Olmsted et al.

R.L. Talbott et al.

C.D. Ackley et al.

J. Virol.

(1990)

T. Ishida et al.

J. Am. Vet. Med. Assoc.

(1989)

N.C. Pedersen et al.

Science

(1987)

J.K. Yamamoto et al.

J. Am. Vet. Med. Assoc.

(1989)

J.K. Yamamoto et al.

Am. J. Vet. Res.

(1988)

O. Narayan et al.

N. MaKi et al.

Arch. Virol.

(1992)

T. Miyazawa et al.

J. Virol.

(1991)

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Feline immunodeficiency virus (FIV) is a widespread lentivirus of domestic cats that causes an acquired immunodeficiency syndrome (AIDS)-like disease similar to human AIDS caused by human immunodeficiency virus. FIV has a complex genome structure including structural, enzymatic and auxiliary genes and regulatory elements. In this article, we review the in vivo roles of some of these FIV auxiliary genes and regulatory elements, especially focusing on the dUTPase, vif, and ORF-A genes and AP-1 binding site in the enhancer region of the long terminal repeat, by comparison with those of other non-primate lentiviruses. These genes and elements are considered to be important for viral replication, immunological response and pathogenesis in cats.
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1997, Virus Research
The effects of treatment with chemical agents or infection with feline viruses on protein-binding properties of the feline immunodeficiency virus (FIV) long terminal repeat (LTR) were examined by gel-mobility-shift assays using oligonucleotides designed to represent putative AP-1 or ATF motif from the FIV LTR. Infection with FIV led to less nuclear proteins binding to the AP-1 and ATF sites, suggesting that proteins binding to the sites were consumed or suppressed by FIV-replication in FIV-infected cells. Nuclear proteins that bind to the AP-1 or ATF site were examined by using extracts from Crandell feline kidney (CRFK) cells treated with TPA (a phorbol ester; a strong activator of protein kinase C) or forskolin (an inducer of cyclic-AMP), or infection with feline herpesvirus type 1 (FHV-1). Although TPA or forskolin treatment moderately increased the level of both proteins that bound to AP-1 and ATF sites, FHV-1 infection markedly changed the protein-binding patterns of the sites. Furthermore, FHV-1-induced proteins that bind adjacent to the transcriptional initiation site of FIV promoter were also observed in FHV-1-infected CRFK cells, suggesting that the FHV-1-induced-proteins affects the transcription of FIV through the AP-1, ATF and leader sequences.
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To examine the regulatory properties of feline immunodeficiency virus (FIV) long terminal repeat (LTR) integrated into host chromatin, Crandell feline kidney cells were stably transfected with the FIV LTR that directs the bacterial chloramphenicol acetyltransferase (CAT) gene. Using these cells, we examined the effects of treatment with several chemical agents, infection with feline viruses, or transfection with effector plasmids expressing FIV gene products on FIV LTR-directed gene expression. Among them, treatment with the phorbol ester (a strong activator of protein kinase C), forskolin (an inducer of cyclic-AMP), 5-azacytidine (a DNA methylation antagonist), or infection with feline herpesvirus type 1 (FHV-1), resulted in induction of CAT activity in the cells. These results suggest that the integrated FIV LTR is stimulated by cellular transcriptional factors induced by phorbol ester, forskolin and FHV-1, and is also inactivated by DNA methylaton. Furthermore, this permanent cell line can be used as a screening system of activators of the FIV LTR.
The feline lymphoid cell line MBM and its use for feline immunodeficiency virus isolation and quantitation
1995, Veterinary Immunology and Immunopathology
We report on the development of a feline T lymphoblastoid cell line obtained from the peripheral blood mononuclear cells (PBMC) of a specific pathogen free cat and designated MBM. The cells are pan-T⁺, CD4⁻ and CD8⁻ and remained interleukin-2-dependent and concanavalin A-dependent throughout the period of observation. MBM cells have proved at least as sensitive as fresh blasts to infection with cell-free stocks of three feline immunodeficiency virus (FIV) isolates. Upon infection, they exhibit a lytic cytopathic effect. Repeated attempts to establish a chronic infection have failed. Using a limiting cell dilution method, it has been shown that MBM cells may be more sensitive than fresh blasts as substrate for isolating FIV from the PBMC of infected cats. These studies have also shown that considerable individual variations exist in the virus loads present in the PBMC of naturally infected cats, and that load size does not appear to correlate with cat age, clinical status, $CD4 CD8$ ratio and titer of serum neutralizing antibody.
The C/EBP Site in the Feline Immunodeficiency Virus (FIV) Long Terminal Repeat (LTR) Is Necessary for Its Efficient Replication and Is Also Involved in the Inhibition of FIV LTR-Directed Gene Expression by Pseudorabies Virus ICP4
1995, Virology
We investigated effects of site-specific mutation of the putative C/EBP binding site in the feline immunodeficiency virus (FIV) long terminal repeat (LTR) on the basal promoter activity in Crandell feline kidney (CRFK) cells and on replication efficiency in CRFK cells and a T-lymphoblastoid cell line, MYA-1 cells. Mutation of the C/EBP site reduced the basal promoter activity in CRFK cells and prevented efficient FIV replication in both CRFK and MYA-1 cells. Gel-mobility-shift assay using nuclear extracts from CRFK and MYA-1 cells revealed that the nuclear factor(s) actually binds to the C/EBP site, but there was a clear difference in the binding patterns to the C/EBP site between CRFK and MYA-1 cell nuclear proteins. Furthermore, we demonstrated that the C/EBP site is necessary for inhibition of FIV LTR-directed gene expression by pseudorabies virus (PRV) ICP4. The C/EBP site is sufficient to confer inhibitory effect by PRV ICP4 on heterologous promoters. These data suggest that the C/EBP site in the FIV LTR is important for the positive regulation of FIV gene expression and replication and is also required for the negative regulation of FIV gene expression by PRV ICP4.
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1995, Bailliere's Clinical Haematology
Feline oncornavirus and lentivirus infections have provided useful models to characterize the virus and host cell factors involved in a variety of marrow suppressive disorders and haematological malignancies. Exciting recent progress has been made in the characterization of the viral genotypic features involved in FeLV-associated diseases. Molecular studies have clearly defined the causal role of variant FeLV env gene determinants in two disorders: the T-lymphocyte cytopathicity and the clinical acute immuno-suppression induced by the FeLV-FAIDS variant and the pure red cell aplasia induced by FeLV-C/Sarma. Variant or enFeLV env sequences also appear to play a role in FeLV-associated lymphomas. Additional studies are required to determine the host cell processes that are perturbed by these variant env gene products. In the case of the FeLV-FAIDS variant, the aberrant env gene products appear to impair superinfection interference, resulting in accumulation of unintegrated viral DNA and cell death. In other cases it is likely that the viral env proteins interact with host products that are important in cell viability and/or proliferation. Understanding of these mechanisms will therefore provide insights to factors involved in normal
The haematological consequences of FIV are quite similar to those associated with HIV. As with HIV, FIV does not appear to directly infect myeloid or erythroid precursors, and the mechanisms of marrow suppression likely involve virus, viral antigen, and/or infected accessory cells in the marrow microenvironment. Studies using in vitro experimental models are required to define the effects of each of these microenvironmental elements on haematopoietic progenitors. As little is known about the molecular mechanisms of FIV pathogenesis, additional studies of disease-inducing FIV strains are needed to identify the genotypic features that correlate with virulent phenotypic features. Finally, experimental FIV infection in cats provides the opportunity to correlate in vivo virological and haematological changes with in vitro observations in a large animal model that closely mimics HIV infection in man.

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Short communicationSequences within the feline immunodeficiency virus long terminal repeat that regulate gene expression and respond to activation by feline herpesvirus type 1

Abstract

Cell

Virology

Virology

Virology

Cell

Cell

Virology

Virology

Cell

J. Virol.

J. Am. Vet. Med. Assoc.

Science

J. Am. Vet. Med. Assoc.

Am. J. Vet. Res.

Arch. Virol.

J. Virol.

Short communication
Sequences within the feline immunodeficiency virus long terminal repeat that regulate gene expression and respond to activation by feline herpesvirus type 1