Determinants flanking the CD4 binding loop modulate macrophage tropism of human immunodeficiency virus type 1 R5 envelopes.

Journal of Virology
Maria J Duenas-DecampPaul R Clapham

Abstract

Human immunodeficiency virus type 1 R5 viruses vary extensively in phenotype. Thus, R5 envelopes (env) in the brain tissue of individuals with neurological complications are frequently highly macrophage-tropic. Macrophage tropism correlates with the capacity of the envelope to exploit low CD4 levels for infection. In addition, the presence of an asparagine at residue 283 within the CD4 binding site has been associated with brain-derived envelopes, increased env-CD4 affinity, and enhanced macrophage tropism. Here, we identify additional envelope determinants of R5 macrophage tropism. We compared highly macrophage-tropic (B33) and non-macrophage-tropic (LN40) envelopes from brain and lymph node specimens of one individual. We first examined the role of residue 283 in macrophage tropism. Introduction of N283 into LN40 (T283N) conferred efficient macrophage infectivity. In contrast, substitution of N283 for the more conserved threonine in B33 had little effect on macrophage infection. Thus, B33 carried determinants for macrophage tropism that were independent of N283. We prepared chimeric B33/LN40 envelopes and used site-directed mutagenesis to identify additional determinants. The determinants of macrophage tropism that were ident...Continue Reading

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Citations

Dec 29, 2010·Current HIV/AIDS Reports·Paul R Gorry, Petronela Ancuta
Jan 13, 2012·Current HIV/AIDS Reports·Kathryn Twigg ArrildtRonald Swanstrom
Oct 29, 2010·Nature Communications·Kuan-Hsiang G HuangPaul Klenerman
Jun 3, 2009·The Journal of Experimental Medicine·Jesus F Salazar-GonzalezGeorge M Shaw
Nov 14, 2013·Retrovirology·Nicholas FrancellaRonald G Collman
Sep 3, 2011·PloS One·Marlén M I Aasa-ChapmanÁine McKnight
Dec 14, 2011·Viruses·Christopher J A Duncan, Quentin J Sattentau
Sep 23, 2014·Journal of Neurovirology·Sarah B JosephRonald Swanstrom
Nov 28, 2007·PLoS Computational Biology·Art F Y PoonSimon D W Frost
Oct 21, 2016·PLoS Pathogens·Sutas SuttiprapaPaul J Brindley
Jul 20, 2014·Bio-protocol·Sarah B JosephRonald Swanstrom
Feb 2, 2018·Journal of Leukocyte Biology·Sarah B Joseph, Ronald Swanstrom
Sep 5, 2015·Journal of Virology·Kathryn T ArrildtRonald Swanstrom

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