Differential evolution of a CXCR4-using HIV-1 strain in CCR5wt/wt and CCR5∆32/∆32 hosts revealed by longitudinal deep sequencing and phylogenetic reconstruction.

Content Provider	Europe PMC
Author	Le, Anh Q. Taylor, Jeremy Dong, Winnie McCloskey, Rosemary Woods, Conan Danroth, Ryan Hayashi, Kanna Milloy, M.-J. Poon, Art F. Y. Brumme, Zabrina L.
Copyright Year	2015
Abstract	Rare individuals homozygous for a naturally-occurring 32 base pair deletion in the CCR5 gene (CCR5∆32/∆32) are resistant to infection by CCR5-using ("R5") HIV-1 strains but remain susceptible to less common CXCR4-using ("X4") strains. The evolutionary dynamics of X4 infections however, remain incompletely understood. We identified two individuals, one CCR5wt/wt and one CCR5∆32/∆32, within the Vancouver Injection Drug Users Study who were infected with a genetically similar X4 HIV-1 strain. While early-stage plasma viral loads were comparable in the two individuals (~4.5-5 log10 HIV-1 RNA copies/ml), CD4 counts in the CCR5wt/wt individual reached a nadir of <20 CD4 cells/mm(3) within 17 months but remained >250 cells/mm(3) in the CCR5∆32/∆32 individual. Ancestral phylogenetic reconstructions using longitudinal envelope-V3 deep sequences suggested that both individuals were infected by a single transmitted/founder (T/F) X4 virus that differed at only one V3 site (codon 24). While substantial within-host HIV-1 V3 diversification was observed in plasma and PBMC in both individuals, the CCR5wt/wt individual's HIV-1 population gradually reverted from 100% X4 to ~60% R5 over ~4 years whereas the CCR5∆32/∆32 individual's remained consistently X4. Our observations illuminate early dynamics of X4 HIV-1 infections and underscore the influence of CCR5 genotype on HIV-1 V3 evolution.
Journal	Scientific Reports [Sci Rep]
Volume Number	5
DOI	10.1038/srep17607
PubMed Central reference number	PMC4668558
PubMed reference number	26631642
e-ISSN	20452322
Language	English
Publisher	Nature Publishing Group
Publisher Date	2015-12-03
Access Restriction	Open
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary