ArticleRetrovirology2014
Partial rescue of V1V2 mutant infectivity by HIV-1 cell-cell transmission supports the domain's exceptional capacity for sequence variation.
Article in Retrovirology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Broadly neutralizing antibody epitopes on HIV-1 particles are exposed after virus interaction with host cells.Journal of virology · 2023Article
- Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Variable infectivity and conserved engagement in cell-to-cell viral transfer by HIV-1 Env from Clade B transmitted founder clones.Virology · 2019Article
- Phenotypic deficits in the HIV-1 envelope are associated with the maturation of a V2-directed broadly neutralizing antibody lineage.PLoS pathogens · 2018Article
- Predicting HIV-1 transmission and antibody neutralization efficacy in vivo from stoichiometric parameters.PLoS pathogens · 2017Article
- Delineating CD4 dependency of HIV-1: Adaptation to infect low level CD4 expressing target cells widens cellular tropism but severely impacts on envelope functionality.PLoS pathogens · 2017Article
- Tracing HIV-1 transmission: envelope traits of HIV-1 transmitter and recipient pairs.Retrovirology · 2016Article
- Cell-Free versus Cell-to-Cell Infection by Human Immunodeficiency Virus Type 1 and Human T-Lymphotropic Virus Type 1: Exploring the Link among Viral Source, Viral Trafficking, and Viral Replication.Journal of virology · 2016Review
- HIV-host interactome revealed directly from infected cells.Nature microbiology · 2016Article
- HIV-1 Cell-Free and Cell-to-Cell Infections Are Differentially Regulated by Distinct Determinants in the Env gp41 Cytoplasmic Tail.Journal of virology · 2015Article
- Capacity of Broadly Neutralizing Antibodies to Inhibit HIV-1 Cell-Cell Transmission Is Strain- and Epitope-Dependent.PLoS pathogens · 2015Article
- HIV cell-to-cell transmission: effects on pathogenesis and antiretroviral therapy.Trends in microbiology · 2015Review
- A native-like SOSIP.664 trimer based on an HIV-1 subtype B env gene.Journal of virology · 2015Article
- Antibody potency relates to the ability to recognize the closed, pre-fusion form of HIV Env.Nature communications · 2015Article
- Different infectivity of HIV-1 strains is linked to number of envelope trimers required for entry.PLoS pathogens · 2015Article
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8 authors.
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No grant is acknowledged in the PubMed record.
Abstract
backgroundVariable loops 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 perform two key functions: ensuring envelope trimer entry competence and shielding against neutralizing antibodies. While preserving entry functionality would suggest a high need for V1V2 sequence optimization and conservation, shielding efficacy is known to depend on a high flexibility of V1V2 giving rise to its substantial sequence variability. How entry competence of the trimer is maintained despite the continuous emergence of antibody escape mutations within V1V2 has not been resolved. Since HIV cell-cell transmission is considered a highly effective means of virus dissemination, we investigated whether cell-cell transmission may serve to enhance infectivity of V1V2 variants with debilitated free virus entry.
resultsIn a detailed comparison of wt and V1V2 mutant envelopes, V1V2 proved to be a key factor in ascertaining free virus infectivity, with V1V2 mutants displaying significantly reduced trimer integrity. Despite these defects, cell-cell transmission was able to partially rescue infectivity of V1V2 mutant viruses. We identified two regions, encompassing amino acids 156 to 160 (targeted by broadly neutralizing antibodies) and 175 to 180 (encompassing the α4β7 binding site) which were particularly prone to free virus infectivity loss upon mutation but maintained infectivity in cell-cell transmission. Of note, V1V2 antibody shielding proved important during both free virus infection and cell-cell transmission.
conclusionsBased on our data we propose a model for V1V2 evolution that centers on cell-cell transmission as a salvage pathway for virus replication. Escape from antibody neutralization may frequently result in V1V2 mutations that reduce free virus infectivity. Cell-cell transmission could provide these escape viruses with sufficiently high replication levels that enable selection of compensatory mutations, thereby restoring free virus infectivity while ensuring antibody escape. Thus, our study highlights the need to factor in cell-cell transmission when considering neutralization escape pathways of HIV-1.
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