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dc.contributor.author Siddappa, NB
dc.contributor.author Watkins, JD
dc.contributor.author Wassermann, KJ
dc.contributor.author Song, R
dc.contributor.author Wang, W
dc.contributor.author Kramer, VG
dc.contributor.author Lakhashe, S
dc.contributor.author Santosuosso, M
dc.contributor.author Poznansky, MC
dc.contributor.author Novembre, FJ
dc.contributor.author Villinger, F
dc.contributor.author Else, JG
dc.contributor.author Montefiori, DC
dc.contributor.author Rasmussen, RA
dc.contributor.author Ruprecht, RM
dc.coverage.spatial United States
dc.date.accessioned 2011-06-21T17:31:33Z
dc.date.issued 2010-07-21
dc.identifier http://www.ncbi.nlm.nih.gov/pubmed/20657739
dc.identifier.citation PLoS One, 2010, 5 (7), pp. e11689 - ?
dc.identifier.uri http://hdl.handle.net/10161/4555
dc.description.abstract BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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 neutralization resistance of SHIV-1157ipd3N4 Env: V2 loops hindering access to the CD4 binding site, shown experimentally with nAb b12. Similar mutations have been linked to decreased neutralization sensitivity in HIV-C strains isolated from humans over time, indicating parallel HIV-C Env evolution in humans and RM. CONCLUSIONS/SIGNIFICANCE: SHIV-1157ipEL-p, the first tier 1 R5 clade C SHIV, and SHIV-1157ipd3N4, its tier 2 counterpart, represent biologically relevant tools for anti-HIV-C vaccine development in primates.
dc.format.extent e11689 - ?
dc.language ENG
dc.language.iso en_US en_US
dc.relation.ispartof PLoS One
dc.relation.isversionof 10.1371/journal.pone.0011689
dc.subject AIDS Vaccines
dc.subject Animals
dc.subject Antibodies, Neutralizing
dc.subject Disease Models, Animal
dc.subject Evolution, Molecular
dc.subject Genes, env
dc.subject HIV-1
dc.subject Macaca mulatta
dc.subject Molecular Sequence Data
dc.subject Mutagenesis, Site-Directed
dc.subject Polymerase Chain Reaction
dc.title 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.
dc.title.alternative en_US
dc.type Journal Article
dc.description.version Version of Record en_US
duke.date.pubdate 2010-7-21 en_US
duke.description.endpage e11689 en_US
duke.description.issue 7 en_US
duke.description.startpage e11689 en_US
duke.description.volume 5 en_US
dc.relation.journal Plos One en_US
pubs.author-url http://www.ncbi.nlm.nih.gov/pubmed/20657739
pubs.issue 7
pubs.organisational-group /Duke
pubs.organisational-group /Duke/School of Medicine
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery
pubs.organisational-group /Duke/School of Medicine/Clinical Science Departments/Surgery/Surgery, Surgical Sciences Section for AIDS Research & Development
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers
pubs.organisational-group /Duke/School of Medicine/Institutes and Centers/Duke Human Vaccine Institute
pubs.publication-status Published online
pubs.volume 5
dc.identifier.eissn 1932-6203

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