scholarly journals Restriction of Feline Immunodeficiency Virus by Ref1, Lv1, and Primate TRIM5α Proteins

2005 ◽  
Vol 79 (24) ◽  
pp. 15175-15188 ◽  
Author(s):  
Dyana T. Saenz ◽  
Wulin Teo ◽  
John C. Olsen ◽  
Eric M. Poeschla
Keyword(s):  
Cell Lines ◽  
Feline Immunodeficiency Virus ◽  
Equine Infectious Anemia Virus ◽  
Lentiviral Vector ◽  
Leukemia Virus ◽  
Human T Cell ◽  
Immunodeficiency Virus ◽  
T Cell Lines ◽  
Hiv 1 ◽  
Vector Transduction

ABSTRACT The Ref1 and Lv1 postentry restrictions in human and monkey cells have been analyzed for lentiviruses in the primate and ungulate groups, but no data exist for the third (feline) group. We compared feline immunodeficiency virus (FIV) to other restricted (human immunodeficiency virus type 1 [HIV-1], equine infectious anemia virus [EIAV]) and unrestricted (NB-tropic murine leukemia virus [NB-MLV]) retroviruses across wide ranges of viral inputs in cells from multiple primate and nonprimate species. We also characterized restrictions conferred to permissive feline and canine cells engineered to express rhesus and human TRIM5α proteins and performed RNA interference (RNAi) against endogenous TRIM5α. We find that expression of rhesus or human TRIM5α proteins in feline cells restricts FIV, impairing pseudotyped vector transduction and viral replication, but rhesus TRIM5α is more restricting than human TRIM5α. Notably, however, canine cells did not support restriction by human TRIM5α and supported minimal restriction by rhesus TRIM5α, suggesting that these proteins may not function autonomously or that a canine factor interferes. Stable RNAi knockdown of endogenous rhesus TRIM5α resulted in marked increases in FIV and HIV-1 infectivities while having no effect on NB-MLV. A panel of nonprimate cell lines varied widely in susceptibility to lentiviral vector transduction, but normalized FIV and HIV-1 vectors varied concordantly. In contrast, in human and monkey cells, relative restriction of FIV compared to HIV-1 varied from none to substantial, with the greatest relative infectivity deficit for FIV vectors observed in human T-cell lines. Endogenous and introduced TRIM5α restrictions of FIV could be titrated by coinfections with FIV, HIV-1, or EIAV virus-like particles. Arsenic trioxide had complex and TRIM5α-independent enhancing effects on lentiviral but not NB-MLV infection. Implications for human gene therapy are discussed.

scholarly journals Murine T Cells Potently Restrict Human Immunodeficiency Virus Infection

2004 ◽  
Vol 78 (22) ◽  
pp. 12537-12547 ◽  
Author(s):  
Jörg G. Baumann ◽  
Derya Unutmaz ◽  
Michael D. Miller ◽  
Sabine K. J. Breun ◽  
Stacy M. Grill ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cells ◽  
T Cell ◽  
Cell Lines ◽  
Viral Gene ◽  
Human T Cell ◽  
Virus Dose ◽  
Immunodeficiency Virus ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT Development of a mouse model for human immunodeficiency virus type 1 (HIV-1) infection has advanced through the progressive identification of host cell factors required for HIV-1 replication. Murine cells lack HIV-1 receptor molecules, do not support efficient viral gene expression, and lack factors necessary for the assembly and release of virions. Many of these blocks have been described using mouse fibroblast cell lines. Here we identify a postentry block to HIV-1 infection in mouse T-cell lines that has not been detected in mouse fibroblasts. While murine fibroblastic lines are comparable to human T-cell lines in permissivity to HIV-1 transduction, infection of murine T cells is 100-fold less efficient. Virus entry occurs efficiently in murine T cells. However, reduced efficiency of the completion of reverse transcription and nuclear transfer of the viral preintegration complex are observed. Although this block has similarities to the restriction of murine retroviruses by Fv1, there is no correlation of HIV-1 susceptibility with cellular Fv1 genotypes. In addition, the block to HIV-1 infection in murine T-cell lines cannot be saturated by a high virus dose. Further studies of this newly identified block may lend insight into the early events of retroviral replication and reveal new targets for antiretroviral interventions.

scholarly journals Human Immunodeficiency Virus Type 1 Replication in the Absence of Integrase-Mediated DNA Recombination: Definition of Permissive and Nonpermissive T-Cell Lines

2001 ◽  
Vol 75 (17) ◽  
pp. 7944-7955 ◽  
Author(s):  
Noriko Nakajima ◽  
Richard Lu ◽  
Alan Engelman
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Lines ◽  
Dna Recombination ◽  
Cell Types ◽  
Class Ii ◽  
Class I ◽  
Immunodeficiency Virus ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT Functional retroviral integrase protein is thought to be essential for productive viral replication. Yet, previous studies differed on the extent to which integrase mutant viruses expressed human immunodeficiency virus type 1 (HIV-1) genes from unintegrated DNA. Although one reason for this difference was that class II integrase mutations pleiotropically affected the viral life cycle, another reason apparently depended on the identity of the infected cell. Here, we analyzed integrase mutant viral infectivities in a variety of cell types. Single-round infectivity of class I integration-specific mutant HIV-1 ranged from <0.03 to 0.3% of that of the wild type (WT) across four different T-cell lines. Based on this approximately 10-fold influence of cell type on mutant gene expression, we examined class I and class II mutant replication kinetics in seven different cell lines and two primary cell types. Unexpectedly, some cell lines supported productive class I mutant viral replication under conditions that restricted class II mutant growth. Cells were defined as permissive, semipermissive, or nonpermissive based on their ability to support the continual passage of class I integration-defective HIV-1. Mutant infectivity in semipermissive and permissive cells as quantified by 50% tissue culture infectious doses, however, was only 0.0006 to 0.005% of that of WT. Since the frequencies of mutant DNA recombination in these lines ranged from 0.023 to <0.093% of the WT, we conclude that productive replication in the absence of integrase function most likely required the illegitimate integration of HIV-1 into host chromosomes by cellular DNA recombination enzymes.

Human T-Cell Leukemia Virus Type I Tax Activates CD69 Gene Expression.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2256-2256
Author(s):  
Chie Ishikawa ◽  
Taeko Okudaira ◽  
Tetsuro Nakazato ◽  
Mariko Tomita ◽  
Naoki Mori
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
Type I ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Human T Cell ◽  
Cd69 Expression ◽  
T Cell Lines

Abstract The human T-cell leukemia virus type I (HTLV-I) is an oncogenic retrovirus that is etiologically linked to the genesis of adult T-cell leukemia (ATL). Emerging evidence suggests that the pathogenicity of ATL involves suppression of the overall immune response, although the underlying mechanism remains unclear. In this study, we demonstrated that HTLV-I transactivator Tax induces the aberrant expression of CD69, an early leukocyte activation molecule that plays an important role in downregulation of the immune response. In a panel of HTLV-I-infected T-cell lines, CD69 expression was highly elevated compared to HTLV-I-negative T-cell lines at both mRNA and protein levels. Furthermore, CD69 expression correlated with Tax expression. Peripheral blood mononuclear cells from ATL patients also showed an increased expression of CD69 compared with controls. In vitro infection of a T-cell line with HTLV-I was associated with CD69 expression in conjunction with the increasing Tax expression. Expression of CD69 was dependent upon Tax expression in the inducible Tax-expressing cell line JPX-9. Tax transactivated the CD69 gene promoter in a transient transfection assay. Using Tax mutants and dominant negative mutants of IκBs, IKKs, NIK, and CREB, we demonstrated that Tax-induced CD69 expression required the NF-κB and CREB signaling pathways. A series of deletion and mutation analyses of the CD69 gene promoter indicated that two NF-κB, two EGR, and a CRE sequences were critical for Tax transactivation. Electrophoretic mobility shift assay showed the formation of specific protein-DNA complexes in HTLV-I-infected T-cell lines. These results suggest that Tax directly transactivated CD69 gene expression, through multiple cis-acting elements and by the interplay of transcription factors of the NF-κB, EGR, and CREB families. Tax-induced CD69 expression may be involved in immune suppression in ATL.

scholarly journals Molecular Characterization of Feline Immunodeficiency Virus Budding

2007 ◽  
Vol 82 (5) ◽  
pp. 2106-2119 ◽  
Author(s):  
Benjamin G. Luttge ◽  
Miranda Shehu-Xhilaga ◽  
Dimiter G. Demirov ◽  
Catherine S. Adamson ◽  
Ferri Soheilian ◽  
...  
Keyword(s):  
Feline Immunodeficiency Virus ◽  
Equine Infectious Anemia Virus ◽  
Binding Motif ◽  
Virus Release ◽  
Related Sequence ◽  
Endosomal Sorting ◽  
Peptide Motifs ◽  
C Terminus ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Infection of domestic cats with feline immunodeficiency virus (FIV) is an important model system for studying human immunodeficiency virus type 1 (HIV-1) infection due to numerous similarities in pathogenesis induced by these two lentiviruses. However, many molecular aspects of FIV replication remain poorly understood. It is well established that retroviruses use short peptide motifs in Gag, known as late domains, to usurp cellular endosomal sorting machinery and promote virus release from infected cells. For example, the Pro-Thr/Ser-Ala-Pro [P(T/S)AP] motif of HIV-1 Gag interacts directly with Tsg101, a component of the endosomal sorting complex required for transport I (ESCRT-I). A Tyr-Pro-Asp-Leu (YPDL) motif in equine infectious anemia virus (EIAV), and a related sequence in HIV-1, bind the endosomal sorting factor Alix. In this study we sought to identify and characterize FIV late domain(s) and elucidate cellular machinery involved in FIV release. We determined that mutagenesis of a PSAP motif in FIV Gag, small interfering RNA-mediated knockdown of Tsg101 expression, and overexpression of a P(T/S)AP-binding fragment of Tsg101 (TSG-5′) each inhibited FIV release. We also observed direct binding of FIV Gag peptides to Tsg101. In contrast, mutagenesis of a potential Alix-binding motif in FIV Gag did not affect FIV release. Similarly, expression of the HIV-1/EIAV Gag-binding domain of Alix (Alix-V) did not disrupt FIV budding, and FIV Gag peptides showed no affinity for Alix-V. Our data demonstrate that FIV relies predominantly on a Tsg101-binding PSAP motif in the C terminus of Gag to promote virus release in HeLa cells, and this budding mechanism is highly conserved in feline cells.

scholarly journals CD4-Independent Infection of Two CD4−/CCR5−/CXCR4+ Pre-T-Cell Lines by Human and Simian Immunodeficiency Viruses

2000 ◽  
Vol 74 (14) ◽  
pp. 6689-6694 ◽  
Author(s):  
Alessandra Borsetti ◽  
Cristina Parolin ◽  
Barbara Ridolfi ◽  
Leonardo Sernicola ◽  
Andrea Geraci ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Chemokine Receptors ◽  
Immunodeficiency Virus ◽  
Cxcr4 Coreceptor ◽  
T Cell Lines ◽  
Hiv 1

ABSTRACT The infection of CD4-negative cells by variants of tissue culture-adapted human immunodeficiency virus type 1 (HIV-1) or HIV-2 strains has been shown to be mediated by the CXCR4 coreceptor. Here we show that two in vitro-established CD4−/CCR5−/CXCR4+ human pre-T-cell lines (A3 and A5) can be productively infected by wild-type laboratory-adapted T-cell-tropic HIV-1 and HIV-2 strains in a CD4-independent, CXCR4-dependent fashion. Despite the absence of CCR5 expression, A3 and A5 cells were susceptible to infection by the simian immunodeficiency viruses SIVmac239 and SIVmac316. Thus, at least in A3 and A5 cells, one or more of the chemokine receptors can efficiently support the entry of HIV and SIV isolates in the absence of CD4. These findings suggest that to infect cells of different compartments, HIV and SIV could have evolved in vivo to bypass CD4 and to interact directly with an alternative receptor.

Human T-Cell Lymphotropic Virus-Type I

1990 ◽  
Vol 11 (6) ◽  
pp. 314-318 ◽  
Author(s):  
Julie Larkin ◽  
John T. Sinnott ◽  
Joshua Weiss ◽  
Douglas A. Holt
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Leukemia Virus ◽  
Type I ◽  
Adult T Cell Leukemia ◽  
Visna Virus ◽  
Human T Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human T-cell lymphotropic virus type-1 (HTLV-I) is a recently recognized retrovirus identified as the cause of adult T-cell leukemia-lymphoma (ATLL) and HTLV-I-associated myelopathy (TSPI HAM). HTLV-I, a member of theRetroviridaefamily of viruses, was first described in 1980 after the isolation of the virus from a patient with a T-cell lymphoma. These pathogenic retroviruses are typically divided into theOncovirinaeandLentivirinae. The oncovirus group, including HTLV-I, HTLV-II and bovine leukemia virus (BLV), is generally associated with tumors. The lentiviruses are associated with immune deficiency and/or neurologic disease, and include agents such as the visna virus of sheep and the human immunodeficiency virus type-1 and -2 HIV-1 and HIV-2).

scholarly journals Apoptosis Induced by the Histone Deacetylase Inhibitor FR901228 in Human T-Cell Leukemia Virus Type 1-Infected T-Cell Lines and Primary Adult T-Cell Leukemia Cells

2004 ◽  
Vol 78 (9) ◽  
pp. 4582-4590 ◽  
Author(s):  
Naoki Mori ◽  
Takehiro Matsuda ◽  
Masayuki Tadano ◽  
Takao Kinjo ◽  
Yasuaki Yamada ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Leukemia Virus ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Induced Apoptosis ◽  
T Cell Lines

ABSTRACT Inhibition of histone deacetylase (HDAC) activity induces growth arrest, differentiation, and, in certain cell types, apoptosis. FR901228, FK228, or depsipeptide, is an HDAC inhibitor effective in T-cell lymphomas. Adult T-cell leukemia (ATL) is caused by human T-cell leukemia virus type 1 (HTLV-1) and remains incurable. We examined whether FR901228 is effective for treatment of ATL by assessing its ability to induce apoptosis of HTLV-1-infected T-cell lines and primary leukemic cells from ATL patients. FR901228 induced apoptosis of Tax-expressing and -unexpressing HTLV-1-infected T-cell lines and selective apoptosis of primary ATL cells, especially those of patients with acute ATL. FR901228 also efficiently reduced the DNA binding of NF-κB and AP-1 in HTLV-1-infected T-cell lines and primary ATL cells and down-regulated the expression of Bcl-xL and cyclin D2, regulated by NF-κB. Although the viral protein Tax is an activator of NF-κB and AP-1, FR901228-induced apoptosis was not associated with reduced expression of Tax. In vivo use of FR901228 partly inhibited the growth of tumors of HTLV-1-infected T cells transplanted subcutaneously in SCID mice. Our results indicated that FR901228 could induce apoptosis of these cells and suppress the expression of NF-κB and AP-1 and suggest that FR901228 could be therapeutically effective in ATL.

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