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Virology. 2012 Nov 25;433(2):296-307. doi: 10.1016/j.virol.2012.08.013. Epub 2012 Sep 3.

Env sequence determinants in CXCR4-using human immunodeficiency virus type-1 subtype C.

Author information

1
Division of Infectious Diseases, Massachusetts General Hospital, Boston, MA, USA.

Abstract

HIV-1 subtype C (HIV-1C) CXCR4-using virus is isolated infrequently and is poorly characterized. Understanding HIV-1C env characteristics has implications for the clinical use of antiretrovirals that target viral entry. A total of 209 env clones derived from 10 samples with mixed CCR5-(R5), CXCR4-using (X4) or dual-tropic HIV-1C were phenotyped for coreceptor usage. Intra-patient X4 and R5 variants generally formed distinct monophyletic phylogenetic clusters. X4 compared to R5 envs had significantly greater amino acid variability and insertions, higher net positive charge, fewer glycosylation sites and increased basic amino acid substitutions in the GPGQ crown. Basic amino acid substitution and/or insertion prior to the crown are highly sensitive characteristics for predicting X4 viruses. Chimeric env functional studies suggest that the V3 loop is necessary but often not sufficient to impart CXCR4 utilization. Our studies provide insights into the unique genotypic characteristics of X4 variants in HIV-1C.

PMID:
22954962
PMCID:
PMC3616623
DOI:
10.1016/j.virol.2012.08.013
[Indexed for MEDLINE]
Free PMC Article

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