title: Selection of unadapted, pathogenic SHIVs encoding newly transmitted HIV-1 envelope proteins.
abstract: 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.
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Gregory Q
authors.initials: GQ
authors.lastname: Del Prete
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
authors.forename: Braiden
authors.initials: B
authors.lastname: Eilers
authors.affiliation: Department of Immunology and Microbiology, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Moldt
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Brandon F
authors.initials: BF
authors.lastname: Keele
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
authors.forename: Marissa
authors.initials: M
authors.lastname: Sampias
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Kelli
authors.initials: K
authors.lastname: Oswald
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Randy
authors.initials: R
authors.lastname: Fast
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Charles M
authors.initials: CM
authors.lastname: Trubey
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Chertova
authors.affiliation: Laboratory Animal Sciences Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smedley
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Celia C
authors.initials: CC
authors.lastname: LaBranche
authors.affiliation: Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Montefiori
authors.affiliation: Department of Immunology and Microbiology, International AIDS Vaccine Initiative Neutralizing Antibody Center and Center for HIV/AIDS Vaccine Immunology and Immunogen Discovery, The Scripps Research Institute, La Jolla, CA 92037, USA; Ragon Institute of MGH, MIT and Harvard, Cambridge, MA 02139, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA.
authors.forename: Marty
authors.initials: M
authors.lastname: Markowitz
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Piatak
authors.affiliation: HIV Drug Resistance Program, National Cancer Institute, Frederick, MD 21702, USA.
authors.forename: Vineet N
authors.initials: VN
authors.lastname: KewalRamani
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA; Laboratory of Retrovirology and Howard Hughes Medical Institute, The Rockefeller University, New York, NY 10016, USA.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory, Frederick, MD 21702, USA. Electronic address: lifsonj@mail.nih.gov.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, NY 10016, USA. Electronic address: thatziio@adarc.org.
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology; D004195:Disease Models, Animal; D015870:Gene Expression; D015483:HIV Antibodies / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015497:HIV-1 / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008251:Macaca; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity; D014776:Virus Cultivation; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism
chemical_list: D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D054299:env Gene Products, Human Immunodeficiency Virus