title: Characterization of molecularly cloned simian-human immunodeficiency viruses causing rapid CD4+ lymphocyte depletion in rhesus monkeys.
abstract: In vivo passage of a chimeric simian-human immunodeficiency virus (SHIV-89.6) expressing the human immunodeficiency virus type 1 (HIV-1) tat, rev, vpu, and env genes generated pathogenic viruses (SHIV-89.6P) inducing rapid CD4+ lymphocyte depletion and AIDS-like illness in rhesus monkeys (K. Reimann, J. T. Li, R. Veazey, M. Halloran, I.-W. Park, G. B. Karlsson, J. Sodroski, and N. L. Letvin, J. Virol. 70:6922-6928, 1996). To characterize the molecular changes responsible for this increase in virulence, infectious proviral clones of SHIV-89.6P isolates were derived. Viruses generated from some of these clones caused a rapid and profound decline of CD4+ lymphocytes in a high percentage of inoculated monkeys. Nucleotide changes potentially responsible for the increased virulence of SHIV-89.6P were limited to the env, tat, or long terminal repeat sequences, with most of the observed changes in env. Nucleotide changes in env altered 12 amino acids in the gp120 and gp41 exterior domains, and a 140-bp deletion in env resulted in the substitution of the carboxyl terminus of the SIVmac gp41 glycoprotein for that of the HIV-1 gp41 glycoprotein. The availability of pathogenic proviral clones should facilitate dissection of the molecular determinants of SHIV-89.6P virulence.
authors.affiliation: Division of Human Retrovirology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
authors.forename: G B
authors.initials: GB
authors.lastname: Karlsson
authors.forename: M
authors.initials: M
authors.lastname: Halloran
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.forename: I W
authors.initials: IW
authors.lastname: Park
authors.forename: R
authors.initials: R
authors.lastname: Gomila
authors.forename: K A
authors.initials: KA
authors.lastname: Reimann
authors.forename: M K
authors.initials: MK
authors.lastname: Axthelm
authors.forename: S A
authors.initials: SA
authors.lastname: Iliff
authors.forename: N L
authors.initials: NL
authors.lastname: Letvin
authors.forename: J
authors.initials: J
authors.lastname: Sodroski
mesh_terms: D000818:Animals; D001483:Base Sequence; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000382:microbiology*; D002678:Chimera; D003001:Cloning, Molecular; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D008212:Lymphocyte Depletion; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D009154:Mutation; D011533:Proviruses / Q000235:genetics / Q000472:pathogenicity; D017384:Sequence Deletion; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity; D015678:Viral Structural Proteins / Q000235:genetics
chemical_list: D015678:Viral Structural Proteins