Emerging Patterns in HIV-1 gp120 Variable Domains in Anatomical Tissues in the Absence of a Plasma Viral Load.
Title | Emerging Patterns in HIV-1 gp120 Variable Domains in Anatomical Tissues in the Absence of a Plasma Viral Load. |
Publication Type | Journal Article |
Year of Publication | 2019 |
Authors | Lamers, SL, Fogel, GB, Nolan, DJ, Barbier, AE, Rose, R, Singer, EJ, Gonzalez-Perez, MPaz, McGrath, MS |
Journal | AIDS Res Hum Retroviruses |
Volume | 35 |
Issue | 6 |
Pagination | 588-596 |
Date Published | 2019 06 |
ISSN | 1931-8405 |
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 | 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. |
DOI | 10.1089/AID.2018.0267 |
Alternate Journal | AIDS Res Hum Retroviruses |
PubMed ID | 30793919 |
PubMed Central ID | PMC6588100 |
Grant List | R01 MH100984 / MH / NIMH NIH HHS / United States R01 NS095749 / NS / NINDS NIH HHS / United States R01 NS107022 / NS / NINDS NIH HHS / United States U24 MH100929 / MH / NIMH NIH HHS / United States |