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Transmitted/founder and chronic subtype C HIV-1 use CD4 and CCR5 receptors with equal efficiency and are not inhibited by blocking the integrin α4β7.
- Source :
-
PLoS pathogens [PLoS Pathog] 2012; Vol. 8 (5), pp. e1002686. Date of Electronic Publication: 2012 May 31. - Publication Year :
- 2012
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Abstract
- Sexual transmission of human immunodeficiency virus type 1 (HIV-1) most often results from productive infection by a single transmitted/founder (T/F) virus, indicating a stringent mucosal bottleneck. Understanding the viral traits that overcome this bottleneck could have important implications for HIV-1 vaccine design and other prevention strategies. Most T/F viruses use CCR5 to infect target cells and some encode envelope glycoproteins (Envs) that contain fewer potential N-linked glycosylation sites and shorter V1/V2 variable loops than Envs from chronic viruses. Moreover, it has been reported that the gp120 subunits of certain transmitted Envs bind to the gut-homing integrin α4β7, possibly enhancing virus entry and cell-to-cell spread. Here we sought to determine whether subtype C T/F viruses, which are responsible for the majority of new HIV-1 infections worldwide, share biological properties that increase their transmission fitness, including preferential α4β7 engagement. Using single genome amplification, we generated panels of both T/F (n = 20) and chronic (n = 20) Env constructs as well as full-length T/F (n = 6) and chronic (n = 4) infectious molecular clones (IMCs). We found that T/F and chronic control Envs were indistinguishable in the efficiency with which they used CD4 and CCR5. Both groups of Envs also exhibited the same CD4+ T cell subset tropism and showed similar sensitivity to neutralization by CD4 binding site (CD4bs) antibodies. Finally, saturating concentrations of anti-α4β7 antibodies failed to inhibit infection and replication of T/F as well as chronic control viruses, although the growth of the tissue culture-adapted strain SF162 was modestly impaired. These results indicate that the population bottleneck associated with mucosal HIV-1 acquisition is not due to the selection of T/F viruses that use α4β7, CD4 or CCR5 more efficiently.
- Subjects :
- Antibodies, Neutralizing immunology
Antibodies, Viral immunology
CD4-Positive T-Lymphocytes cytology
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
Cells, Cultured
Cloning, Molecular
HIV Envelope Protein gp120 chemistry
HIV Envelope Protein gp120 immunology
HIV Envelope Protein gp120 metabolism
HIV Infections metabolism
HIV-1 immunology
HIV-1 metabolism
Host-Pathogen Interactions
Humans
Integrins immunology
Mucous Membrane virology
Neutralization Tests
Viral Tropism
Virus Internalization
Virus Replication
CD4 Antigens metabolism
HIV Infections transmission
HIV-1 pathogenicity
Integrins metabolism
Receptors, CCR5 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7374
- Volume :
- 8
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- PLoS pathogens
- Publication Type :
- Academic Journal
- Accession number :
- 22693444
- Full Text :
- https://doi.org/10.1371/journal.ppat.1002686