Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder clade C HIV-1 envelopes.
Abstract
Simian-human immunodeficiency viruses (SHIVs) that mirror natural transmitted/founder
(T/F) viruses in man are needed for evaluation of HIV-1 vaccine candidates in nonhuman
primates. Currently available SHIVs contain HIV-1 env genes from chronically-infected
individuals and do not reflect the characteristics of biologically relevant HIV-1
strains that mediate human transmission. We chose to develop clade C SHIVs, as clade
C is the major infecting subtype of HIV-1 in the world. We constructed 10 clade C
SHIVs expressing Env proteins from T/F viruses. Three of these ten clade C SHIVs (SHIV
KB9 C3, SHIV KB9 C4 and SHIV KB9 C5) replicated in naïve rhesus monkeys. These three
SHIVs are mucosally transmissible and are neutralized by sCD4 and several HIV-1 broadly
neutralizing antibodies. However, like natural T/F viruses, they exhibit low Env reactivity
and a Tier 2 neutralization sensitivity. Of note, none of the clade C T/F SHIVs elicited
detectable autologous neutralizing antibodies in the infected monkeys, even though
antibodies that neutralized a heterologous Tier 1 HIV-1 were generated. Challenge
with these three new clade C SHIVs will provide biologically relevant tests for vaccine
protection in rhesus macaques.
Type
Journal articleSubject
HIV-1 Clade CMucosal transmission
SHIV
Transmitted/founder Env
Animals
Gene Expression Regulation, Viral
HEK293 Cells
HIV-1
Humans
Mutation
Phylogeny
Simian Acquired Immunodeficiency Syndrome
Simian Immunodeficiency Virus
Viral Envelope Proteins
Viremia
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https://hdl.handle.net/10161/10205Published Version (Please cite this version)
10.1016/j.virol.2014.10.032Publication Info
Asmal, Mohammed; Luedemann, Corinne; Lavine, Christy L; Mach, Linh V; Balachandran,
Harikrishnan; Brinkley, Christie; ... Santra, Sampa (2015). Infection of monkeys by simian-human immunodeficiency viruses with transmitted/founder
clade C HIV-1 envelopes. Virology, 475. pp. 37-45. 10.1016/j.virol.2014.10.032. Retrieved from https://hdl.handle.net/10161/10205.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Thomas Norton Denny
Professor in Medicine
Thomas N. Denny, MSc, M.Phil, is the Chief Operating Officer of the Duke Human Vaccine
Institute (DHVI), Associate Dean for Duke Research and Discovery @RTP, and a Professor
of Medicine in the Department of Medicine at Duke University Medical Center. He is
also an Affiliate Member of the Duke Global Health Institute. Previously, he served
on the Health Sector Advisory Council of the Duke University Fuquay School of Business.
Prior to joining Duke, he was an Associate Professor of Pathology, Labo
Barton Ford Haynes
Frederic M. Hanes Distinguished Professor of Medicine
The Haynes lab is studying host innate and adaptive immune responses to the human
immunodeficiency virus (HIV), tuberculosis (TB), and influenza in order to find the
enabling technology to make preventive vaccines against these three major infectious
diseases. Mucosal Immune Responses in Acute HIV Infection The Haynes lab is working
to determine why broadly neutralizing antibodies are rarely made in acute HIV infection
(AHI), currently a major obstacle in the de
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