title: HIV-1-induced AIDS in monkeys.
abstract: Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8(+) cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and ultimately caused marked CD4(+) T cell depletion and AIDS-defining conditions. Transient treatment with an antibody to CD8 during acute HIV-1 infection caused rapid progression to AIDS, whereas untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection.
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org.
authors.forename: Theodora
authors.initials: T
authors.lastname: Hatziioannou
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Gregory Q
authors.initials: GQ
authors.lastname: Del Prete
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, 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, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jacob D
authors.initials: JD
authors.lastname: Estes
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Matthew W
authors.initials: MW
authors.lastname: McNatt
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Bitzegeio
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Alice
authors.initials: A
authors.lastname: Raymond
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Anthony
authors.initials: A
authors.lastname: Rodriguez
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA.
authors.forename: Fabian
authors.initials: F
authors.lastname: Schmidt
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: C
authors.initials: C
authors.lastname: Mac Trubey
authors.affiliation: Laboratory Animal Sciences Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA.
authors.forename: Jeremy
authors.initials: J
authors.lastname: Smedley
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, 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. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org.
authors.forename: Vineet N
authors.initials: VN
authors.lastname: KewalRamani
authors.affiliation: AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory, Frederick, MD 21702, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Lifson
authors.affiliation: Aaron Diamond AIDS Research Center, 455 First Avenue, New York, NY 10016, USA. Laboratory of Retrovirology, The Rockefeller University, 455 First Avenue, New York, NY 10016, USA. Howard Hughes Medical Institute, 455 First Avenue, New York, NY 10016, USA. thatziio@adarc.org vineet.kewalramani@nih.gov lifsonj@mail.nih.gov pbienias@adarc.org.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Bieniasz
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000635:transmission / Q000821:virology*; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000276:immunology*; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008212:Lymphocyte Depletion; D008254:Macaca nemestrina / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication; D000086082:Viroporin Proteins
chemical_list: D016827:CD8 Antigens; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins