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Unique phenotypic characteristics of recently transmitted HIV-1 subtype C envelope glycoprotein gp120: Use of CXCR6 coreceptor by transmitted founder viruses
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2018 (English)In: Journal of Virology, ISSN 0022-538X, E-ISSN 1098-5514, Vol. 92, no 9, article id e00063-18Article in journal (Refereed) Published
Abstract [en]

Adequate information on the precise molecular and biological composition of the viral strains that establish HIV infection in the human host will provide effective means of immunization against HIV infection. In an attempt to identify the transmitted founder (TF) virus and differentiate the biological properties and infectious potential of the TF virus from those of the population of the early transmitted viruses, 250 patient-derived gp120 envelope glycoproteins were cloned in pMN-K7- Luc-IRESs-NefΔgp120 to obtain chimeric viruses. Samples were obtained from eight infants who had recently become infected with HIV through mother-to-child transmission (MTCT) and two adults who acquired infection through the heterosexual route and were in the chronic stage of infection. Among the 250 clones tested, 65 chimeric viruses were infectious, and all belonged to HIV-1 subtype C. The 65 clones were analyzed for molecular features of the envelope, per-infectious-particle infectivity, coreceptor tropism, drug sensitivity, and sensitivity to broadly neutralizing antibodies. Based on genotypic and phenotypic analysis of the viral clones, we identified 10 TF viruses from the eight infants. The TF viruses were characterized by shorter V1V2 regions, a reduced number of potential N-linked glycosylation sites, and a higher infectivity titer compared to the virus variants from the adults in the chronic stage of infection. CXCR6 coreceptor usage, in addition to that of the CCR5 coreceptor, which was used by all 65 chimeric viruses, was identified in 13 viruses. The sensitivity of the TF variants to maraviroc and a standard panel of neutralizing monoclonal antibodies (VRC01, PG09, PG16, and PGT121) was found to be much lower than that of the virus variants from the adults in the chronic stage of infection.

Place, publisher, year, edition, pages
American Society for Microbiology , 2018. Vol. 92, no 9, article id e00063-18
Keywords [en]
Amino acid diversity, Coreceptor tropism, Human immunodeficiency virus, Mother-to-child transmission, Resistance to neutralization, Transmitted founder virus
National Category
Microbiology in the medical area
Identifiers
URN: urn:nbn:se:kth:diva-227588DOI: 10.1128/JVI.00063-18ISI: 000430281200005PubMedID: 29491151Scopus ID: 2-s2.0-85045525538OAI: oai:DiVA.org:kth-227588DiVA, id: diva2:1205786
Funder
Swedish Research Council, 201701330Stockholm County Council, ALF 20160074Knut and Alice Wallenberg FoundationScience for Life Laboratory - a national resource center for high-throughput molecular bioscience
Note

QC 20180515

Available from: 2018-05-15 Created: 2018-05-15 Last updated: 2018-05-15Bibliographically approved

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