Expression of human immunodeficiency virus 1 (HIV-1) envelope gene products transcribed from a heterologous promoter. Kinetics of HIV-1 envelope processing in transfected cells.

ABSTRACT Here we report that the N-pyridinylmethyl cyclam analog AMD3451 has antiviral activity against a wide variety of R5, R5/X4, and X4 strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2 (50% inhibitory concentration [IC50] ranging from 1.2 to 26.5 μM) in various T-cell lines, CCR5- or CXCR4-transfected cells, peripheral blood mononuclear cells (PBMCs), and monocytes/macrophages. AMD3451 also inhibited R5, R5/X4, and X4 HIV-1 primary clinical isolates in PBMCs (IC50, 1.8 to 7.3 μM). A PCR-based viral entry assay revealed that AMD3451 blocks R5 and X4 HIV-1 infection at the virus entry stage. AMD3451 dose-dependently inhibited the intracellular Ca2+ signaling induced by the CXCR4 ligand CXCL12 in T-lymphocytic cells and in CXCR4-transfected cells, as well as the Ca2+ flux induced by the CCR5 ligands CCL5, CCL3, and CCL4 in CCR5-transfected cells. The compound did not interfere with chemokine-induced Ca2+ signaling through CCR1, CCR2, CCR3, CCR4, CCR6, CCR9, or CXCR3 and did not induce intracellular Ca2+ signaling by itself at concentrations up to 400 μM. In freshly isolated monocytes, AMD3451 inhibited the Ca2+ flux induced by CXCL12 and CCL4 but not that induced by CCL2, CCL3, CCL5, and CCL7. The CXCL12- and CCL3-induced chemotaxis was also dose-dependently inhibited by AMD3451. Furthermore, AMD3451 inhibited CXCL12- and CCL3L1-induced endocytosis in CXCR4- and CCR5-transfected cells. AMD3451, in contrast to the specific CXCR4 antagonist AMD3100, did not inhibit but enhanced the binding of several anti-CXCR4 monoclonal antibodies (such as clone 12G5) at the cell surface, pointing to a different interaction with CXCR4. AMD3451 is the first low-molecular-weight anti-HIV agent with selective HIV coreceptor, CCR5 and CXCR4, interaction.

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APOBEC3H haplotypes and HIV-1 pro-viral vif DNA sequence diversity in early untreated human immunodeficiency virus–1 infection

Human Immunology ◽

10.1016/j.humimm.2010.12.008 ◽

2011 ◽

Vol 72 (3) ◽

pp. 207-212 ◽

Cited By ~ 18

Author(s):

P.A. Gourraud ◽

A. Karaouni ◽

J.M. Woo ◽

T. Schmidt ◽

J.R. Oksenberg ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Dna Sequence ◽

Sequence Diversity ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Human Immunodeficiency Virus 1

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Development of a homology model for clade A human immunodeficiency virus type 1 gp120 to localize temporal substitutions arising in recently infected women

Journal of General Virology ◽

10.1099/vir.0.79974-0 ◽

2004 ◽

Vol 85 (6) ◽

pp. 1479-1484

Author(s):

Mary Poss ◽

David C. Holley ◽

Roman Biek ◽

Harold Cox ◽

John Gerdes

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Envelope Gene ◽

Virus Population ◽

Gene Sequences ◽

Virus Diversity ◽

Immunodeficiency Virus ◽

Hiv 1

The virus population transmitted by a human immunodeficiency virus type 1 (HIV-1) infected individual undergoes restriction and subsequent diversification in the new host. However, in contrast to men, who have limited virus diversity at seroconversion, there is measurable diversity in viral envelope gene sequences in women infected with clade A HIV-1. In this study, virus sequence diversity in three unrelated, clade A infected women preceding and shortly after seroconversion was evaluated. It was demonstrated that there is measurable evolution of envelope gene sequences over this time interval. Furthermore, in each of the three individuals, amino acid substitutions arose at five or six positions in sequences derived at or shortly after seroconversion relative to sequences obtained from the seronegative sample. Presented here is a model of clade A gp120 to determine the location of substitutions that appeared as the virus population became established in three clade A HIV-1 infected women.

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Human immunodeficiency virus 1. Predominance of a group-specific neutralizing epitope that persists despite genetic variation.

Journal of Experimental Medicine ◽

10.1084/jem.170.5.1681 ◽

1989 ◽

Vol 170 (5) ◽

pp. 1681-1695 ◽

Cited By ~ 27

Author(s):

I Berkower ◽

G E Smith ◽

C Giri ◽

D Murphy

Keyword(s):

Genetic Diversity ◽

Human Immunodeficiency Virus ◽

Neutralizing Antibodies ◽

Neutralizing Epitope ◽

Vaccine Strategy ◽

Disease Pathogenesis ◽

Immunodeficiency Virus ◽

High Degree ◽

Hiv 1 ◽

Human Immunodeficiency Virus 1

HIV-1 is known to show a high degree of genetic diversity, which may have major implications for disease pathogenesis and prevention. If every divergent isolate represented a distinct serotype, then effective vaccination might be impossible. However, using a sensitive new plaque-forming assay for HIV-1, we have found that most infected patients make neutralizing antibodies, predominantly to a group-specific epitope shared among three highly divergent isolates. This epitope persists among divergent isolates and rarely mutates, despite the rapid overall mutation rate of HIV-1, suggesting that it may participate in an essential viral function. These findings, plus the rarity of reinfections among these patients, suggest that HIV-1 may be more susceptible to a vaccine strategy based on a group-specific neutralizing epitope than was previously suspected.

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Tat–Human Immunodeficiency Virus-1 Induces Human Monocyte Chemotaxis by Activation of Vascular Endothelial Growth Factor Receptor-1

Blood ◽

10.1182/blood.v90.4.1365.1365_1365_1372 ◽

1997 ◽

Vol 90 (4) ◽

pp. 1365-1372 ◽

Cited By ~ 3

Author(s):

Stefania Mitola ◽

Silvano Sozzani ◽

Walter Luini ◽

Luca Primo ◽

Alessandro Borsatti ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Human Immunodeficiency Virus ◽

Growth Factor ◽

Tyrosine Kinase ◽

Vascular Endothelial ◽

Immunodeficiency Virus ◽

Monocyte Chemotaxis ◽

Endothelial Growth Factor ◽

Hiv 1 ◽

Human Immunodeficiency Virus 1

Human immunodeficiency virus-1 (HIV-1) Tat protein can be released by infected cells and activates mesenchymal cells. Among these, monocytes respond to Tat by migrating into tissues and releasing inflammatory mediators. In the present study, we have examined the molecular mechanism of monocyte activation by Tat, showing that this viral protein signals inside the cells through the tyrosine kinase receptor for vascular endothelial growth factor encoded by fms-like tyrosine kinase gene (VEGFR-1/Flt-1). Subnanomolar concentrations of Tat induced monocyte chemotaxis, which was inhibited by cell preincubation with vascular-endothelial growth factor-A (VEGF-A). This desensitisation was specific for VEGF-A, because it not was observed with FMLP. In addition, the soluble form of VEGFR-1 specifically inhibited polarization and migration induced by Tat and VEGF-A, thus confirming the common use of this receptor. Binding studies performed at equilibrium by using radiolabeled Tat showed that monocytes expressed a unique class of binding site, with a kd of approximately 0.2 nmol/L. The binding of radiolabeled Tat to monocyte surface and the cross-linking to a protein of 150 kD was inhibited specifically by an excess of cold Tat or VEGF-A. Western blot analysis with an antibody anti–VEGFR-1/Flt-1 performed on monocyte phosphoproteins immunoprecipitated by an monoclonal antibody antiphosphotyrosine showed that Tat induced a rapid phosphorylation in tyrosine residue of the 150-kD VEGFR-1/Flt-1. Taken together, these results suggest that biologic activities of HIV-1 Tat in human monocytes may, at least in part, be elicited by activation of VEGFR-1/Flt-1.

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Human immunodeficiency virus 1 (HIV-1) reverse transcriptase (RT)

Emerging Therapeutic Targets ◽

10.1517/14728222.2.2.239 ◽

1998 ◽

Vol 2 (2) ◽

pp. 239-243

Author(s):

Elias Argyris ◽

Yvonne Paterson

Keyword(s):

Human Immunodeficiency Virus ◽

Reverse Transcriptase ◽

Immunodeficiency Virus ◽

Hiv 1 ◽

Human Immunodeficiency Virus 1

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Kinetics of Human Immunodeficiency Virus Type 1 Decay following Entry into Resting CD4+ T Cells

Journal of Virology ◽

10.1128/jvi.79.4.2199-2210.2005 ◽

2005 ◽

Vol 79 (4) ◽

pp. 2199-2210 ◽

Cited By ~ 137

Author(s):

Yan Zhou ◽

Haili Zhang ◽

Janet D. Siliciano ◽

Robert F. Siliciano

Keyword(s):

Gene Expression ◽

Human Immunodeficiency Virus ◽

T Cells ◽

Human Immunodeficiency Virus Type ◽

Reverse Transcription ◽

Half Life ◽

Immunodeficiency Virus ◽

Kinetics Of ◽

Hiv 1

ABSTRACT In untreated human immunodeficiency virus type 1 (HIV-1) infection, most viral genomes in resting CD4+ T cells are not integrated into host chromosomes. This unintegrated virus provides an inducible latent reservoir because cellular activation permits integration, virus gene expression, and virus production. It remains controversial whether HIV-1 is stable in this preintegration state. Here, we monitored the fate of HIV-1 in resting CD4+ cells by using a green fluorescent protein (GFP) reporter virus carrying an X4 envelope. After virus entry into resting CD4+ T cells, both rescuable virus gene expression, visualized with GFP, and rescuable virion production, assessed by p24 release, decayed with a half-life of 2 days. In these cells, reverse transcription goes to completion over 2 to 3 days, and 50% of the viruses that have entered undergo functional decay before reverse transcription is complete. We distinguished two distinct but closely related factors contributing to loss of rescuable virus. First, some host cells undergo virus-induced apoptosis upon viral entry, thereby reducing the amount of rescuable virus. Second, decay processes directly affecting the virus both before and after the completion of reverse transcription contribute to the loss of rescuable virus. The functional half-life of full-length, integration-competent reverse transcripts is only 1 day. We propose that rapid intracellular decay processes compete with early steps in viral replication in infected CD4+ T cells. Decay processes dominate in resting CD4+ T cells as a result of the slow kinetics of reverse transcription and blocks at subsequent steps. Therefore, the reservoir of unintegrated HIV-1 in recently infected resting CD4+ T cells is highly labile.

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Human immunodeficiency virus types 1 and 2 have different replication kinetics in human primary macrophage culture

Journal of General Virology ◽

10.1099/vir.0.81391-0 ◽

2006 ◽

Vol 87 (2) ◽

pp. 411-418 ◽

Cited By ~ 20

Author(s):

David Marchant ◽

Stuart J. D. Neil ◽

Áine McKnight

Keyword(s):

Human Immunodeficiency Virus ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Steady Rate ◽

Immunodeficiency Virus ◽

Load Characteristics ◽

Kinetics Of ◽

Hiv 1

This study compares the replication of primary isolates of human immunodeficiency virus type 2 (HIV-2) and type 1 (HIV-1) in monocyte-derived macrophages (MDMs). Eleven HIV-2 and five HIV-1 primary isolates that use CCR5, CXCR4 or both coreceptors to enter cells were included. Regardless of coreceptor preference, 10 of 11 HIV-2 viruses could enter, reverse transcribe and produce fully infectious virus in MDMs with efficiency equal to that in peripheral blood mononuclear cells. However, the kinetics of replication of HIV-2 compared with HIV-1 over time were distinct. HIV-2 had a burst of virus replication 2 days after infection that resolved into an apparent ‘latent state’ at day 3. HIV-1, however, continued to produce infectious virions at a lower, but steady, rate throughout the course of infection. These results may have implications for the lower pathogenesis and viral-load characteristics of HIV-2 infection.

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