A Naturally Occurring Variation in the Proline-Rich Region Does Not Attenuate Human Immunodeficiency Virus Type 1 Nef Function

ABSTRACT We analyzed human immunodeficiency virus type 1 (HIV-1) Nef variants to further evaluate the functional relevance of the R71T substitution previously proposed to attenuate viral replication (Fackler et al., Curr. Biol. 11:1294-1299, 2001). Our results demonstrate that this variation in the proline-rich region does not significantly affect the functional activity of Nef or HIV-1 infectivity or replication.

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Naturally Occurring Human Immunodeficiency Virus Type 1 Long Terminal Repeats Have a Frequently Observed Duplication That Binds RBF-2 and Represses Transcription

Journal of Virology ◽

10.1128/jvi.72.8.6465-6474.1998 ◽

1998 ◽

Vol 72 (8) ◽

pp. 6465-6474 ◽

Cited By ~ 26

Author(s):

Mario Clemente Estable ◽

Brendan Bell ◽

Martin Hirst ◽

Ivan Sadowski

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Binding Sites ◽

Naturally Occurring ◽

Immunodeficiency Virus ◽

Aids Study ◽

Hiv 1 ◽

In Cells

ABSTRACT Approximately 38% of human immunodeficiency virus type 1 (HIV-1)-infected patients within the Vancouver Lymphadenopathy-AIDS Study have proviruses bearing partial 15- to 34-nucleotide duplications upstream of the NF-κB binding sites within the 5′ long terminal repeat (LTR). This most frequent naturally occurring length polymorphism (MFNLP) of the HIV-1 5′ LTR encompasses potential binding sites for several candidate transcription factors, including TCF-1α/hLEF, c-Ets, AP-4, and Ras-responsive binding factor 2 (RBF-2) (M. C. Estable et al., J. Virol. 70:4053–4062, 1996). RBF-2 and an apparently related factor, RBF-1, bind to at least fourcis elements within the LTR which are required for full transcriptional responsiveness to protein-tyrosine kinases and v-Ras (B. Bell and I. Sadowski, Oncogene 13:2687–2697, 1996). Here we demonstrate that representative MFNLPs from two patients specifically bind RBF-2. In both cases, deletion of the MFNLP caused elevated LTR-directed transcription in cells expressing RBF-2 but not in cells with undetectable RBF-2. RBF-1, but not RBF-2, appears to contain the Ets transcription factor family member GABPα/GABPβ1. Taken together with the fact that every MFNLP from a comparative study of over 500 LTR sequences from 42 patients contains a predicted binding site for RBF-2, our data suggest that the MFNLP is selected in vivo because it provides a duplicated RBF-2 cis element, which may limit transcription in monocytes and activated T cells.

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Naturally Occurring Amino Acid Polymorphisms in Human Immunodeficiency Virus Type 1 (HIV-1) Gag p7NC and the C-Cleavage Site Impact Gag-Pol Processing by HIV-1 Protease

Virology ◽

10.1006/viro.2001.1184 ◽

2002 ◽

Vol 292 (1) ◽

pp. 137-149 ◽

Cited By ~ 11

Author(s):

Maureen M. Goodenow ◽

Gregory Bloom ◽

Stephanie L. Rose ◽

Steven M. Pomeroy ◽

Patricia O. O'Brien ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Amino Acid ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Cleavage Site ◽

Naturally Occurring ◽

Immunodeficiency Virus ◽

Hiv 1

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A Tyrosine-Rich Region in the N Terminus of CCR5 Is Important for Human Immunodeficiency Virus Type 1 Entry and Mediates an Association between gp120 and CCR5

Journal of Virology ◽

10.1128/jvi.72.2.1160-1164.1998 ◽

1998 ◽

Vol 72 (2) ◽

pp. 1160-1164 ◽

Cited By ~ 156

Author(s):

Michael Farzan ◽

Hyeryun Choe ◽

Luis Vaca ◽

Kathleen Martin ◽

Ying Sun ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Chemokine Receptors ◽

Target Cells ◽

Rich Region ◽

Immunodeficiency Virus ◽

Chemokine Receptor Ccr5 ◽

Hiv 1

ABSTRACT Human immunodeficiency virus type 1 (HIV-1) requires the presence of specific chemokine receptors in addition to CD4 to enter target cells. The chemokine receptor CCR5 is used by the macrophage-tropic strains of HIV-1 that predominate during the asymptomatic stages of infection. Here we identify a small tyrosine-rich region of CCR5 proximal to the N-terminal cysteine that is critical for entry of macrophage-tropic and dual-tropic variants of HIV-1. HIV-1 infection of cells expressing CCR5 mutants with changes in this region was substantially reduced compared with the infection of cells bearing wild-type CCR5. Simian immunodeficiency virus (SIVmac239) entry was also ablated on a subset of these mutants but enhanced on others. These differences in virus entry were correlated with the relative ability of soluble, monomeric HIV-1 and SIVmac239 gp120 glycoproteins to bind the CCR5 mutants. These results identify a region of CCR5 that is necessary for the physical association of the gp120 envelope glycoprotein with CCR5 and for HIV-1 infection.

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