Determination of Coreceptor Usage of Human Immunodeficiency Virus Type 1 from Patient Plasma Samples by Using a Recombinant Phenotypic Assay

Trouplin, Virginie; Salvatori, Francesca; Cappello, Francesco; Obry, Véronique; Brelot, Anne; Heveker, Nikolaus; Alizon, Marc; Scarlatti, Gabriella; Clavel, François; Mammano, Fabrizio

doi:10.1128/jvi.75.1.251-259.2001

Cited by 100 publications

(100 citation statements)

References 77 publications

(59 reference statements)

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“…Clonal virus systems, based on infectious chimeras or Env-pseudotyped viruses, are becoming an increasingly common way to study entry inhibitors, including neutralizing antibodies (9,29,38,43,45,65,91,110,112,113). We noticed, however, that quantitative, but not qualitative, estimates of AD101 resistance differed when they were derived by using clonal, infectious chimeric viruses and uncloned isolates, even with the same target cells.…”

Section: Vol 78 2004 Hiv-1 Escape From a Ccr5 Antagonist 2803mentioning

confidence: 72%

Genetic and Phenotypic Analyses of Human Immunodeficiency Virus Type 1 Escape from a Small-Molecule CCR5 Inhibitor

Kuhmann

Pugach

Kunstman

et al. 2004

J Virol

187

218

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, Proc. Natl. Acad. Sci. USA 99:395-400, 2002). The escape mutant, CC101.19, continued to use CCR5 for entry, but it was at least 20,000-fold more resistant to AD101 than the parental virus, CC1/85. We have now cloned the env genes from the the parental and escape mutant isolates and made chimeric infectious molecular clones that fully recapitulate the phenotypes of the corresponding isolates. Sequence analysis of the evolution of the escape mutants suggested that the most relevant changes were likely to be in the V3 loop of the gp120 glycoprotein. We therefore made a series of mutant viruses and found that full AD101 resistance was conferred by four amino acid changes in V3. Each change individually caused partial resistance when they were introduced into the V3 loop of a CC1/85 clone, but their impact was dependent on the gp120 context in which they were made. We assume that these amino acid changes alter how the HIV-1 Env complex interacts with CCR5. Perhaps unexpectedly, given the complete dependence of the escape mutant on CCR5 for entry, monomeric gp120 proteins expressed from clones of the fully resistant isolate failed to bind to CCR5 on the surface of L1.2-CCR5 cells under conditions where gp120 proteins from the parental virus and a partially AD101-resistant virus bound strongly. Hence, the full impact of the V3 substitutions may only be apparent at the level of the native Env complex.Several members of a new class of inhibitors based on blocking human immunodeficiency virus type 1 (HIV-1) entry into target cells are now in, or approaching, human clinical trials (8,52,77,80,85,90,98). These various compounds antagonize different stages in the multistep pathway by which HIV-1 fuses with susceptible cells. For example, the CD4-immunoglobulin G2 protein (CD4-IgG2; PRO 542) attaches to the viral envelope glycoprotein gp120 to prevent it from interacting with the CD4 receptor (3, 109). The T-20 and T-1249 peptides act later, by inhibiting conformational changes in the viral gp41 glycoprotein that are necessary for membrane fusion to be initiated (8,40,72,115). All these inhibitors cause plasma viremia reductions in HIV-1-infected people (8,49,53,62,66,71,80).A step in the entry process intermediate between gp120-CD4 attachment and gp41 conformational changes involves a coreceptor for gp120 (21,31,37,85,98). Thus, after gp120 has bound to CD4, it changes conformation to enable it to bind to a coreceptor from the G-protein-coupled receptor superfamily (21,31,37,85,98,107,116). The most physiologically relevant coreceptors are the chemokine receptors CCR5 or CXCR4, the former used by HIV-1 strains that usually dominate early in infection and the latter used by viruses that sometimes emerge several years later or that are detectable only transiently (21,31,85,99,122). The presence of viruses able to use CXCR4 (X4 strains) is associated with an accelerated disease course, due in part to the loss of naive CD4 ϩ T cells that express CXCR4 but not CCR5 (32,44,69). Viruses using CCR5 (R5 strains) target memory CD4 ϩ...

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Section: Vol 78 2004 Hiv-1 Escape From a Ccr5 Antagonist 2803mentioning

confidence: 72%

Genetic and Phenotypic Analyses of Human Immunodeficiency Virus Type 1 Escape from a Small-Molecule CCR5 Inhibitor

Kuhmann

Pugach

Kunstman

et al. 2004

J Virol

187

218

View full text Add to dashboard Cite

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“…Infection of these cell lines with R5-and X4-tropic HIV-1 strains, respectively, results in the induction of ␤-galactosidase, which can be conveniently detected by a colorimetric assay (51). For patient T28, two viral clones were found to use CCR5 (T28-R5-1 and T28-R5-2) and three clones used CXCR4 (T28-X4-1, T28-X4-2, and T28-X4-3), whereas for patient T5, three clones were R5 (T5-R5-1, T5-R5-2, and T5-R5-3) and two were able to use both CCR5 and CXCR4 (T5-R5X4-1 and T5-R5X4-2).…”

Section: Vol 79 2005 Neutralization Sensitivity Of Hiv-1 Variants 1mentioning

confidence: 99%

Human Immunodeficiency Virus Type 1 Variants Isolated from Single Plasma Samples Display a Wide Spectrum of Neutralization Sensitivity

Skrabal

Saragosti

Labernardière³

et al. 2005

J Virol

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“…We designed several replication competent viral clones, carrying envelope sequences issued from different variants that coexisted in the plasma viral population (see Materials and Methods for further details). We determined the tropism of these viral clones by infection of U373-MG-CD4-CCR5 and U373-MG-CD4-CXCR4 reporter cell lines (data not shown) (53). For further studies, we selected two X4 (termed T28-X4-1 and T28-X4-2, respectively) and one R5 (T28-R5-1) viral clones (Skrabal et al, unpublished).…”

Section: Absence Of Long-term Storage Of Incoming Infectious Hiv In Tmentioning

confidence: 99%

Covert Human Immunodeficiency Virus Replication in Dendritic Cells and in DC-SIGN-Expressing Cells Promotes Long-Term Transmission to Lymphocytes

Nobile

Petit

Moris

et al. 2005

J Virol

Self Cite

129

139

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HIV-1 virions are efficiently captured by monocyte-derived immature dendritic cells (iDCs), as well as by cell lines expressing the lectin DC-SIGN. Viral infectivity can be retained for several days, and even enhanced, before transmission to CD4 ؉ lymphocytes. The role of DC-SIGN in viral retention and enhancement of infection is not fully understood and varies according to the cell line expressing the lectin. We studied here the mechanisms underlying this process. We focused our study on X4-tropic human immunodeficiency virus (HIV) strains, since they were widely believed not to replicate in iDCs. However, we first show that X4 HIV replicates covertly and slowly in iDCs. This is also the case in Raji-DC-SIGN cells, which are classically used to study HIV transmission. We used either single-cycle or replicative HIV and measured viral RT and replication to further demonstrate that transfer of incoming virions from iDCs or DC-SIGN ؉ cells occurs only on the short-term (i.e., a few hours after viral exposure). There is no long-term storage of original HIV particles in these cells. A few days after viral exposure, replicative viruses, and not single-cycle virions, are transmitted to CD4؉ cells. The cell-type-dependent activity of DC-SIGN reflects the ability of HIV to replicate covertly in some cells, and not in others.

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Determination of Coreceptor Usage of Human Immunodeficiency Virus Type 1 from Patient Plasma Samples by Using a Recombinant Phenotypic Assay

Cited by 100 publications

References 77 publications

Genetic and Phenotypic Analyses of Human Immunodeficiency Virus Type 1 Escape from a Small-Molecule CCR5 Inhibitor

Genetic and Phenotypic Analyses of Human Immunodeficiency Virus Type 1 Escape from a Small-Molecule CCR5 Inhibitor

Human Immunodeficiency Virus Type 1 Variants Isolated from Single Plasma Samples Display a Wide Spectrum of Neutralization Sensitivity

Covert Human Immunodeficiency Virus Replication in Dendritic Cells and in DC-SIGN-Expressing Cells Promotes Long-Term Transmission to Lymphocytes

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