Characterization of a thymus-tropic HIV-1 isolate from a rapid progressor: role of the envelope

Virology
Eric G MeissnerLishan Su

Abstract

Loss of T cell homeostasis usually precedes the onset of AIDS. We hypothesized that rapid progressors may be transmitted with HIV-1 that is particularly able to perturb T cell homeostasis. To this end, we have tested two transmitted, syncytium-inducing (SI) viral isolates from a rapid progressor in two thymus models. One of the isolates (R3A) exhibited markedly rapid kinetics of replication and thymocyte depletion. These phenotypes mapped to the envelope, as a recombinant NL4-3 virus encoding the R3A envelope had similar phenotypes, even in the absence of nef. Notably, the viruses with high pathogenic activity in the thymus (R3A and NL4-R3A) did not show enhanced replication or cytopathicity in PHA-stimulated PBMCs. Furthermore, NL4-R3A did not enhance replication of the coinfected NL4-3 virus in the thymus, suggesting an intrinsic advantage of the R3A envelope. The R3A envelope showed higher entry activity in infecting human T cells and in depleting CD4+ thymocytes when expressed in trans. These data suggest that SI viruses with unique envelope functions which can overcome barriers to transmission may hasten disease progression by perturbing T cell homeostasis.

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Citations

Aug 30, 2008·Immunologic Research·Derek HolmesLishan Su
Dec 31, 2010·Journal of Virology·Guiqing HuKenneth H Roux
Sep 26, 2013·Organic & Biomolecular Chemistry·Jonathan G RudickWilliam F DeGrado
Aug 11, 2005·Current HIV/AIDS Reports·Rohan Hazra, Crystal Mackall
Jul 7, 2009·Journal of Theoretical Biology·Shingo IwamiYasuhiro Takeuchi
May 12, 2009·Immunology Letters·Shingo IwamiTomoyuki Miura
Oct 6, 2007·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Vanessa A EvansSharon R Lewin
Apr 15, 2015·Assay and Drug Development Technologies·Mariana MarinGregory B Melikyan
Nov 23, 2013·The Journal of Biological Chemistry·Anjali JoshiHimanshu Garg
Jan 15, 2016·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anjali JoshiHimanshu Garg
May 10, 2018·The Journal of Experimental Medicine·Norbert PardiDrew Weissman

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