title: 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.
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Asmal
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Corinne
authors.initials: C
authors.lastname: Luedemann
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Christy L
authors.initials: CL
authors.lastname: Lavine
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Linh V
authors.initials: LV
authors.lastname: Mach
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Harikrishnan
authors.initials: H
authors.lastname: Balachandran
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Christie
authors.initials: C
authors.lastname: Brinkley
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Denny
authors.affiliation: BIOQUAL Inc., Rockville, MD 20852, USA.
authors.forename: Mark G
authors.initials: MG
authors.lastname: Lewis
authors.affiliation: BIOQUAL Inc., Rockville, MD 20852, USA.
authors.forename: Hanne
authors.initials: H
authors.lastname: Anderson
authors.affiliation: Advanced BioScience Laboratories, Inc., Rockville, MD 20850, USA.
authors.forename: Ranajit
authors.initials: R
authors.lastname: Pal
authors.affiliation: Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Devin
authors.initials: D
authors.lastname: Sok
authors.affiliation: Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Khoa
authors.initials: K
authors.lastname: Le
authors.affiliation: Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Pauthner
authors.affiliation: University of Pennsylvania, Department of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Beatrice H
authors.initials: BH
authors.lastname: Hahn
authors.affiliation: University of Pennsylvania, Department of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: George M
authors.initials: GM
authors.lastname: Shaw
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: University of Pennsylvania, Department of Medicine and Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Norman L
authors.initials: NL
authors.lastname: Letvin
authors.affiliation: Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Burton
authors.affiliation: Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Sodroski
authors.affiliation: Duke Human Vaccine Institute, Duke University School of Medicine, Durham, NC 27710, USA.
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA. Electronic address: ssantra@bidmc.harvard.edu.
authors.forename: Sampa
authors.initials: S
authors.lastname: Santra
mesh_terms: D000818:Animals; D015967:Gene Expression Regulation, Viral / Q000502:physiology; D057809:HEK293 Cells; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics*; D014759:Viral Envelope Proteins / Q000378:metabolism*; D014766:Viremia
chemical_list: D014759:Viral Envelope Proteins
keywords: HIV-1 Clade C; Mucosal transmission; SHIV; Transmitted/founder Env