title: Pathogenic infection of Rhesus macaques by an evolving SIV-HIV derived from CCR5-using envelope genes of acute HIV-1 infections.
abstract: For studies on vaccines and therapies for HIV disease, SIV-HIV chimeric viruses harboring the HIV-1 env gene (SHIVenv) remain the best virus in non-human primate models. However, there are still very few SHIVenv viruses that can cause AIDS in non-CD8-depleted animals. In the present study, a recently created CCR5-using SHIVenv_B3 virus with env gene derived from acute/early HIV-1 infections (AHI) successfully established pathogenic infection in macaques. Through a series of investigations on the evolution, mutational profile, and phenotype of the virus and the resultant humoral immune response in infected rhesus macaques, we found that the E32K mutation in the Env C1 domain was associated with macaque pathogenesis, and that the electrostatic interactions in Env may favor E32K at the gp120 N terminus and "lock" the binding to heptad repeat 1 of gp41 in the trimer and produce a SHIVenv with increased fitness and pathogenesis during macaque infections.
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: Sophie
authors.initials: S
authors.lastname: Lane
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Meijuan
authors.initials: M
authors.lastname: Tian
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Nickel
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Colin
authors.initials: C
authors.lastname: Venner
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Brennan
authors.initials: B
authors.lastname: Dirk
authors.affiliation: Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Jimmy
authors.initials: J
authors.lastname: Dikeakos
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: Linh
authors.initials: L
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: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Adam
authors.initials: A
authors.lastname: Buzby
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Srinivas
authors.initials: S
authors.lastname: Rao
authors.affiliation: Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Norman
authors.initials: N
authors.lastname: Letvin
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.
authors.forename: Yong
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Infectious Diseases and HIV Medicine, Case Western Reserve University, Cleveland, OH 44106, USA; Department of Microbiology and Immunology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada. Electronic address: earts@uwo.ca.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Arts
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D004195:Disease Models, Animal; D019143:Evolution, Molecular; D015686:Gene Products, env / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000235:genetics / Q000276:immunology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D056724:Immunity, Humoral; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010802:Phylogeny; D019713:Receptors, CCR5 / Q000235:genetics / Q000276:immunology; D011991:Receptors, Virus / Q000235:genetics / Q000276:immunology; D016415:Sequence Alignment; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D014774:Virulence
chemical_list: D000914:Antibodies, Viral; D015686:Gene Products, env; D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D011991:Receptors, Virus
keywords: Envelope; Pathogenesis; Rhesus macaque; SIV-HIV chimeric viruses