Variation in HIV-1 R5 macrophage-tropism correlates with sensitivity to reagents that block envelope: CD4 interactions but not with sensitivity to other entry inhibitors.

Retrovirology
Paul J PetersPaul R Clapham

Abstract

HIV-1 R5 viruses cause most of the AIDS cases worldwide and are preferentially transmitted compared to CXCR4-using viruses. Furthermore, R5 viruses vary extensively in capacity to infect macrophages and highly macrophage-tropic variants are frequently identified in the brains of patients with dementia. Here, we investigated the sensitivity of R5 envelopes to a range of inhibitors and antibodies that block HIV entry. We studied a large panel of R5 envelopes, derived by PCR amplification without culture from brain, lymph node, blood and semen. These R5 envelopes conferred a wide range of macrophage tropism and included highly macrophage-tropic variants from brain and non-macrophage-tropic variants from lymph node. R5 macrophage-tropism correlated with sensitivity to inhibition by reagents that inhibited gp120:CD4 interactions. Thus, increasing macrophage-tropism was associated with increased sensitivity to soluble CD4 and to IgG-CD4 (PRO 542), but with increased resistance to the anti-CD4 monoclonal antibody (mab), Q4120. These observations were highly significant and are consistent with an increased affinity of envelope for CD4 for macrophage-tropic envelopes. No overall correlations were noted between R5 macrophage-tropism and ...Continue Reading

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Citations

Jan 13, 2012·Current HIV/AIDS Reports·Kathryn Twigg ArrildtRonald Swanstrom
Apr 3, 2009·Current Opinion in HIV and AIDS·Donald E Mosier
Aug 14, 2009·Retrovirology·Rachel Van DuyneFatah Kashanchi
Dec 14, 2011·Viruses·Christopher J A Duncan, Quentin J Sattentau
Mar 19, 2014·Critical Reviews in Microbiology·George Panos, Dionysios Christos Watson
Apr 29, 2015·Current HIV/AIDS Reports·Maria M BednarRonald Swanstrom
Apr 21, 2018·Viruses·Craig MillerSue VandeWoude
Sep 5, 2015·Journal of Virology·Kathryn T ArrildtRonald Swanstrom

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Methods Mentioned

BETA
glycosylation
PCR

Software Mentioned

Excel
Prism

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