R5 clade C SHIV strains with tier 1 or 2 neutralization sensitivity: tools to dissect env evolution and to develop AIDS vaccines in primate models.

PloS One
Nagadenahalli B SiddappaRuth M Ruprecht

Abstract

HIV-1 clade C (HIV-C) predominates worldwide, and anti-HIV-C vaccines are urgently needed. Neutralizing antibody (nAb) responses are considered important but have proved difficult to elicit. Although some current immunogens elicit antibodies that neutralize highly neutralization-sensitive (tier 1) HIV strains, most circulating HIVs exhibiting a less sensitive (tier 2) phenotype are not neutralized. Thus, both tier 1 and 2 viruses are needed for vaccine discovery in nonhuman primate models. We constructed a tier 1 simian-human immunodeficiency virus, SHIV-1157ipEL, by inserting an "early," recently transmitted HIV-C env into the SHIV-1157ipd3N4 backbone [1] encoding a "late" form of the same env, which had evolved in a SHIV-infected rhesus monkey (RM) with AIDS. SHIV-1157ipEL was rapidly passaged to yield SHIV-1157ipEL-p, which remained exclusively R5-tropic and had a tier 1 phenotype, in contrast to "late" SHIV-1157ipd3N4 (tier 2). After 5 weekly low-dose intrarectal exposures, SHIV-1157ipEL-p systemically infected 16 out of 17 RM with high peak viral RNA loads and depleted gut CD4+ T cells. SHIV-1157ipEL-p and SHIV-1157ipd3N4 env genes diverge mostly in V1/V2. Molecular modeling revealed a possible mechanism for the increased ...Continue Reading

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Citations

Aug 2, 2013·Journal of Virology·Thaddeus M DavenportKelly K Lee
Sep 18, 2012·Critical Reviews in Microbiology·Derrick LouzRob C Hoeben
Nov 15, 2011·Current Opinion in Virology·Samir K LakhasheRuth M Ruprecht
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Aug 16, 2016·Clinical & Translational Immunology·Vladimir VigdorovichD Noah Sather
Dec 5, 2014·Journal of Virology·Hui-Wen ChangDan H Barouch
Dec 12, 2018·Expert Review of Vaccines·Mohammad Arif Rahman, Marjorie Robert-Guroff
Nov 28, 2019·Vaccines·Ruth M RuprechtRajesh Thippeshappa
Jun 2, 2016·Proceedings of the National Academy of Sciences of the United States of America·Hui LiGeorge M Shaw
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May 16, 2018·AIDS·Siqi GongRuth M Ruprecht
Apr 20, 2017·Current Opinion in HIV and AIDS·Ruth M Ruprecht, Samir K Lakhashe

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Datasets Mentioned

BETA
HM585377

Methods Mentioned

BETA
transfection
PCR
glycosylation
X-ray
biopsies

Software Mentioned

LANL N - Glycosite
CHARMM
Discovery Studio
GraphPad
Prism®

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