Generation and evaluation of clade C simian-human immunodeficiency virus challenge stocks
Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, MA, United States; Harvard Medical School, Boston, MA, United States; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA, United States; Division of Medical Virology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Seattle Biomedical Research Institute, Seattle, WA, United States; Fred Hutchinson Cancer Research Center, Seattle, WA, United States
The development of a panel of mucosally transmissible simian-human immunodeficiency virus (SHIV) challenge stocks from multiple virus clades would facilitate preclinical evaluation of candidate HIV-1 vaccines and therapeutics. The majority of SHIV stocks that have been generated to date have been derived from clade B HIV-1 env sequences from viruses isolated during chronic infection and typically required serial animal-to-animal adaptation for establishing mucosal transmissibility and pathogenicity. To capture essential features of mucosal transmission of cladeCviruses, we produced a series of SHIVs with early cladeCHIV-1 env sequences from acutely HIV-1-infected individuals from South Africa. SHIV-327c and SHIV-327cRM expressed env sequences that were 99.7 to 100% identical to the original HIV-1 isolate and did not require in vivo passaging for mucosal infectivity. These challenge stocks infected rhesus monkeys efficiently by both intrarectal and intravaginal routes, replicated to high levels during acute infection, and established chronic setpoint viremia in 13 of 17 (76%) infected animals. The SHIV-327cRM challenge stock was also titrated for both single, highdose intrarectal challenges and repetitive, low-dose intrarectal challenges in rhesus monkeys. These SHIV challenge stocks should facilitate the preclinical evaluation of vaccines and other interventions aimed at preventing cladeCHIV-1 infection. © 2015, American Society for Microbiology.
concanavalin A; adult; animal cell; Article; CD4 lymphocyte count; CD4+ T lymphocyte; cladistics; controlled study; disease severity; female; gene amplification; human; human cell; Human immunodeficiency virus 1; immunophenotyping; male; molecular cloning; nonhuman; nucleotide sequence; pathogenicity; phenotype; real time polymerase chain reaction; sequence alignment; Simian immunodeficiency virus; viremia; virus infectivity; virus load; virus neutralization; virus purification; virus replication; virus strain; virus titration; virus transmission; animal; disease model; genetics; growth, development and aging; Human immunodeficiency virus 1; isolation and purification; mucosa; rhesus monkey; Simian immunodeficiency virus; virology; virulence; Animalia; Human immunodeficiency virus 1; Macaca mulatta; Simian-Human immunodeficiency virus; Animals; Disease Models, Animal; Female; HIV-1; Humans; Macaca mulatta; Male; Mucous Membrane; Simian Immunodeficiency Virus; Virulence
AI078526, NIH, National Institutes of Health; AI084794, NIH, National Institutes of Health; AI095985, NIH, National Institutes of Health; AI096040, NIH, National Institutes of Health