Differential human immunodeficiency virus expression in CD4+ cloned lymphocytes: from viral latency to replication.

ABSTRACT Human astrocytes can be infected with human immunodeficiency virus type 1 (HIV-1) in vitro and in vivo, but, in contrast to T lymphocytes and macrophages, virus expression is inefficient. To investigate the HIV-1 life cycle in human fetal astrocytes, we infected cells with HIV-1 pseudotyped with envelope glycoproteins of either amphotropic murine leukemia virus or vesicular stomatitis virus. Infection by both pseudotypes was productive and long lasting and reached a peak of 68% infected cells and 1.7 μg of viral p24 per ml of culture supernatant 7 days after virus inoculation and then continued with gradually declining levels of virus expression through 7 weeks of follow-up. This contrasted with less than 0.1% HIV-1 antigen-positive cells and 400 pg of extracellular p24 per ml at the peak of astrocyte infection with native HIV-1. Cell viability and growth kinetics were similar in infected and control cells. Northern blot analysis revealed the presence of major HIV-1 RNA species of 9, 4, and 2 kb in astrocytes exposed to pseudotyped (but not wild-type) HIV-1 at 2, 14, and 28 days after infection. Consistent with productive infection, the 9- and 4-kb viral transcripts in astrocytes infected by pseudotyped HIV-1 were as abundant as the 2-kb mRNA during 4 weeks of follow-up, and both structural and regulatory viral proteins were detected in infected cells by immunoblotting or cell staining. The progeny virus released by these cells was infectious. These results indicate that the major barrier to HIV-1 infection of primary astrocytes is at virus entry and that astrocytes have no intrinsic intracellular restriction to efficient HIV-1 replication.

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A platelet-activating factor antagonist, RP 55778, inhibits cytokine-dependent induction of human immunodeficiency virus expression in chronically infected promonocytic cells.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.90.6.2537 ◽

1993 ◽

Vol 90 (6) ◽

pp. 2537-2541 ◽

Cited By ~ 22

Author(s):

D. Weissman ◽

G. Poli ◽

A. Bousseau ◽

A. S. Fauci

Keyword(s):

Human Immunodeficiency Virus ◽

Platelet Activating Factor ◽

Immunodeficiency Virus ◽

Virus Expression ◽

Factor Antagonist ◽

Promonocytic Cells

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Mapping of tetraspanin-enriched microdomains that can function as gateways for HIV-1

The Journal of Cell Biology ◽

10.1083/jcb.200508165 ◽

2006 ◽

Vol 173 (5) ◽

pp. 795-807 ◽

Cited By ~ 157

Author(s):

Sascha Nydegger ◽

Sandhya Khurana ◽

Dimitry N. Krementsov ◽

Michelangelo Foti ◽

Markus Thali

Keyword(s):

Human Immunodeficiency Virus ◽

Envelope Glycoprotein ◽

Viral Assembly ◽

Biological Processes ◽

Gag Protein ◽

Endosomal Sorting ◽

Immunodeficiency Virus ◽

Virus Expression ◽

Hiv 1

Specific spatial arrangements of proteins and lipids are central to the coordination of many biological processes. Tetraspanins have been proposed to laterally organize cellular membranes via specific associations with each other and with distinct integrins. Here, we reveal the presence of tetraspanin-enriched microdomains (TEMs) containing the tetraspanins CD9, CD63, CD81, and CD82 at the plasma membrane. Fluorescence and immunoelectron microscopic analyses document that the surface of HeLa cells is covered by several hundred TEMs, each extending over a few hundred nanometers and containing predominantly two or more tetraspanins. Further, we reveal that the human immunodeficiency virus type 1 (HIV-1) Gag protein, which directs viral assembly and release, accumulates at surface TEMs together with the HIV-1 envelope glycoprotein. TSG101 and VPS28, components of the mammalian ESCRT1 (endosomal sorting complex required for transport), which is part of the cellular extravesiculation machinery critical for HIV-1 budding, are also recruited to cell surface TEMs upon virus expression, suggesting that HIV-1 egress can be gated through these newly mapped microdomains.

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Interleukin 2 induces CD8+ T cell-mediated suppression of human immunodeficiency virus replication in CD4+ T cells and this effect overrides its ability to stimulate virus expression.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.92.24.10985 ◽

1995 ◽

Vol 92 (24) ◽

pp. 10985-10989 ◽

Cited By ~ 48

Author(s):

A. L. Kinter ◽

S. M. Bende ◽

E. C. Hardy ◽

R. Jackson ◽

A. S. Fauci

Keyword(s):

Human Immunodeficiency Virus ◽

T Cells ◽

T Cell ◽

Virus Replication ◽

Cd4 T Cells ◽

Interleukin 2 ◽

Cd8 T Cell ◽

Human Immunodeficiency Virus Replication ◽

Immunodeficiency Virus ◽

Virus Expression

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Impact on Genetic Networks in Human Macrophages by a CCR5 Strain of Human Immunodeficiency Virus Type 1

Journal of Virology ◽

10.1128/jvi.78.21.11477-11486.2004 ◽

2004 ◽

Vol 78 (21) ◽

pp. 11477-11486 ◽

Cited By ~ 31

Author(s):

Carter R. Coberley ◽

James J. Kohler ◽

Joseph N. Brown ◽

Joseph T. Oshier ◽

Henry V. Baker ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Expression Patterns ◽

Human Macrophages ◽

Hierarchical Agglomerative Cluster ◽

Immunodeficiency Virus ◽

Virus Expression ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) impacts multiple lineages of hematopoietic cells, including lymphocytes and macrophages, either by direct infection or indirectly by perturbations of cell networks, leading to generalized immune deficiency. We designed a study to discover, in primary human macrophages, sentinel genetic targets that are impacted during replication over the course of 7 days by a CCR5-using virus. Expression of mRNA and proteins in virus- or mock-treated macrophages from multiple donors was evaluated. Hierarchical agglomerative cluster analysis grouped into distinct temporal expression patterns >900 known human genes that were induced or repressed at least fourfold by virus. Expression of more than one-third of the genes was induced rapidly by day 2 of infection, while other genes were induced at intermediate (day 4) or late (day 7) time points. More than 200 genes were expressed exclusively in either virus- or mock-treated macrophage cultures, independent of the donor, providing an unequivocal basis to distinguish an effect by virus. HIV-1 altered levels of mRNA and/or protein for diverse cellular programs in macrophages, including multiple genes that can contribute to a transition in the cell cycle from G1 to G2/M, in contrast to expression in mock-treated macrophages of genes that maintain G0/G1. Virus treatment activated mediators of cell cycling, including PP2A, which is impacted by Vpr, as well as GADD45 and BRCA1, potentially novel targets for HIV-1. The results identify interrelated programs conducive to optimal HIV-1 replication and expression of genes that can contribute to macrophage dysfunction.

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