Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Nov 1;64(3):249-53.
doi: 10.1097/QAI.0b013e3182a06ddd.

Early infection HIV-1 envelope V1-V2 genotypes do not enhance binding or replication in cells expressing high levels of α4β7 integrin

Behzad Etemad  1 , Oscar A Gonzalez, Sean McDonough, Victor Pena-Cruz, Manish Sagar
Affiliations

Early infection HIV-1 envelope V1-V2 genotypes do not enhance binding or replication in cells expressing high levels of α4β7 integrin

Behzad Etemad et al. J Acquir Immune Defic Syndr. .

Abstract

It has been postulated that HIV-1 envelope properties, such as shorter and less-glycosylated V1-V2 loops commonly observed among non-subtype B early-transmitted viruses, promote utilization of the gut homing integrin α4β7. This property potentially confers an advantage to some HIV-1 variants early after acquisition. We found that replication-competent recombinant viruses incorporating HIV-1 subtype A compact and less-glycosylated early versus chronic phase V1-V2 loops demonstrated no significant difference in binding to α4β7 high CD8⁺ T cells or replication in α4β7 high CD4⁺ T cells. Integrin α4β7 usage does not select for shorter less-glycosylated envelopes during transmission.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest: No author has a commercial or other association that might pose a conflict of interest.

Figures

Figure 1
Figure 1
Virus binding and replication in cells expressing the α4β7 integrin. A and B, Flow cytometric analysis of α4β7 cell surface expression on CD8+ T cells (A) and CD4+ T cells (B) cultured with and without retinoic acid (RA). The α4β7 integrin was probed with phyocoerythrin (PE) conjugated anti-mouse integrin β7 antibody (clone FIB27) (BioLegend). An unrelated IgG1 antibody served as the isotype control. These are representative examples from multiple independent cell isolations. C and D, Bal envelope HIV-1 (gray bars) and SF162 (white bars) attachment to CD8+ T cells (C) and replication in CD4+ T cells (D) in the presence or absence of retinoic acid and antibodies specific for α4β7 (Act 1 (10ug) and 2B4 (2 ug) (R&D Systems)), and β1 (10 ug) (P4G11(Millipore)). Bars show mean values with standard error generated from 6 independent experiments with cells from 6 different donors. In each experiment, percent binding and replication is calculated relative to the cells cultured in the presence of RA and without any antibody (set at 100%).
Figure 2
Figure 2
Influence of longitudinal V1-V2 loop changes on α4β7 utilization. A, Table lists the V1-V2 loop ID, length and number of predicted N-linked glycosylation sites (PNGS). In each V1-V2 loop name, the first part lists the subject ID. The duration (in months) from estimated acquisition date to the time of sample collection from which the V1-V2 loop was obtained is indicated in the brackets of each V1-V2 loop name. The envelope sequences have been described in detail previously., B and C, Attachment to CD8+ T cells (B) and replication in CD4+ T cells (C) among early (black bars) and chronic (white bars) infection V1-V2 envelope loop chimeras. In each experiment, percent binding and replication is calculated relative to the envelope chimera with the early infection V1-V2 loop (set at 100%). D, Percent replication in the presence relative to the absence of 10 ug of Act 1. Bars show mean values with standard error generated from a minimum of 3 and 6 independent binding and replication experiments respectively. In each independent experiment, cells were obtained from different donors.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mehandru S, Poles MA, Tenner-Racz K, et al. Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract. J Exp Med. 2004;200:761–770. - PMC - PubMed
    1. Haase AT. Perils at mucosal front lines for HIV and SIV and their hosts. Nat Rev Immunol. 2005;5:783–792. - PubMed
    1. Arthos J, Cicala C, Martinelli E, et al. HIV-1 envelope protein binds to and signals through integrin alpha4beta7, the gut mucosal homing receptor for peripheral T cells. Nat Immunol. 2008;9:301–309. - PubMed
    1. Cicala C, Martinelli E, McNally JP, et al. The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc Natl Acad Sci U S A. 2009;106:20877–20882. - PMC - PubMed
    1. Nawaz F, Cicala C, Van Ryk D, et al. The genotype of early-transmitting HIV gp120s promotes alpha (4) beta(7)-reactivity, revealing alpha (4) beta(7) +/CD4+ T cells as key targets in mucosal transmission. PLoS Pathog. 2011;7:e1001301. - PMC - PubMed

Publication types

MeSH terms