Date Published:
2019 06

Publication Type:
Journal Article

Authors:

S.L. Lamers
G.B. Fogel
D.J. Nolan
A.E. Barbier
R. Rose
E.J. Singer
M.Paz Gonzalez-Perez
M.S. McGrath

Secondary:
AIDS Res Hum Retroviruses

Volume:
35

Pagination:
588-596

Issue:
6

PMID:
30793919

URL:
https://pubmed.ncbi.nlm.nih.gov/30793919

DOI:
10.1089/AID.2018.0267

Keywords:
Anti-HIV Agents;Autopsy;Disease Reservoirs;External;HIV Envelope Protein gp120;HIV Infections;HIV-1;Humans;Peptide Fragments;Sequence Analysis, DNA;Viral Load

Abstract:
<p>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.</p>