TY - JOUR
T1 - Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins
AU - Del Prete, Gregory Q.
AU - Ailers, Braiden
AU - Moldt, Brian
AU - Keele, Brandon F.
AU - Estes, Jacob D.
AU - Rodriguez, Anthony
AU - Sampias, Marissa
AU - Oswald, Kelli
AU - Fast, Randy
AU - Trubey, Charles M.
AU - Chertova, Elena
AU - Smedley, Jeremy
AU - Labranche, Celia C.
AU - Montefiori, David C.
AU - Burton, Dennis R.
AU - Shaw, George M.
AU - Markowitz, Marty
AU - Piatak, Michael
AU - Kewalramani, Vineet N.
AU - Bieniasz, Paul D.
AU - Lifson, Jeffrey D.
AU - Hatziioannou, Theodora
N1 - Funding Information:
We are grateful to Vicky Coalter, Adam Wiles, Rodney Wiles, and Donald Johnson for assistance with study coordination and processing of nonhuman primate blood and tissues and to Florian Douam and Melinda Ng for assistance in optimizing SHIV cloning procedures. This work was supported by grants from the NIH; R21AI093255 (to T.H.), R37AI64003, and R01AI50111 (to P.D.B.); by the Howard Hughes Medical Institute; by NIAID-NIH Contract No. HHSN27201100016C (to D.C.M.); and in part with federal funds from the National Cancer Institute, National Institutes of Health, under Contract No. HHSN261200800001E (to J.D.L.). Histology support was provided by the Pathology/Histotechnology Laboratory core service located at the Frederick National Laboratory for Cancer Research, Leidos Biomedical Research, Inc., Frederick, MD. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.
Publisher Copyright:
© 2014 Elsevier Inc.
PY - 2014/9/10
Y1 - 2014/9/10
N2 - Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.
AB - Infection of macaques with chimeric viruses based on SIVMAC but expressing the HIV-1 envelope (Env) glycoproteins (SHIVs) remains the most powerful model for evaluating prevention and therapeutic strategies against AIDS. Unfortunately, only a few SHIVs are currently available. Furthermore, their generation has required extensive adaptation of the HIV-1 Env sequences in macaques so they may not accurately represent HIV-1 Env proteins circulating in humans, potentially limiting their translational utility. We developed a strategy for generating large numbers of SHIV constructs expressing Env proteins from newly transmitted HIV-1 strains. By inoculating macaques with cocktails of multiple SHIV variants, we selected SHIVs that can replicate and cause AIDS-like disease in immunologically intact rhesus macaques without requiring animal-to-animal passage. One of these SHIVs could be transmitted mucosally. We demonstrate the utility of the SHIVs generated by this method for evaluating neutralizing antibody administration as a protection against mucosal SHIV challenge.
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U2 - 10.1016/j.chom.2014.08.003
DO - 10.1016/j.chom.2014.08.003
M3 - Article
C2 - 25211081
AN - SCOPUS:84907693726
SN - 1931-3128
VL - 16
SP - 412
EP - 418
JO - Cell Host and Microbe
JF - Cell Host and Microbe
IS - 3
ER -