Emerging Patterns in HIV-1 gp120 Variable Domains in Anatomical Tissues in the Absence of a Plasma Viral Load

AIDS Research and Human Retroviruses
S L LamersMichael S McGrath

Abstract

The HIV envelope protein contains five hypervariable domains (V1-V5) that are fundamental for cell entry. We contrasted modifications in the variable domains derived from a panel of 24 tissues from 7 subjects with no measurable plasma viral load (NPVL) to variable domains from 76 tissues from 15 subjects who had a detectable plasma viral load (PVL) at death. NPVL subject's V1 and V2 domains were usually highly length variable, whereas length variation in PVL sequences was more conserved. Longer V1s contained more charged residues, whereas longer V2s were more glycosylated. Structural analysis demonstrated V1/V2 charge, and N-site additions/subtractions were localized to the CD4 binding pocket. Diversified envelopes in tissues during therapy may represent a mechanism for HIV persistence in tissues, as binding pocket complexity is associated with HIV that may escape neutralization, whereas shorter envelopes are associated with increased infectivity. Further analysis of tissue-derived envelope sequences may enable better understanding of potential immunological approaches targeting the persistent HIV reservoir.

References

Jan 25, 2008·BMC Bioinformatics·Yang Zhang
Jun 3, 2009·The Journal of Experimental Medicine·Jesus F Salazar-GonzalezGeorge M Shaw
Oct 16, 2010·Methods in Molecular Biology·Leona W AyersDebra L Garcia
Sep 22, 2016·Sarcoma·Susanna L LamersMichael S McGrath
Nov 1, 2017·AIDS Research and Human Retroviruses·David J NolanMichael S McGrath

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Datasets Mentioned

BETA
KU708891
HM001816

Methods Mentioned

BETA
glycosylation

Software Mentioned

Geneious
TASSER
V2
SeqLogo
MacPyMOL
MacWizard
Excel

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