title: A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has offered cytotropism.
abstract: We have examined both the sequence changes in the LTR, gag, vif, vpr, vpx, tat, rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of chimeric simian-human immunodeficiency virus (SHIV) isolated from the cerebrospinal fluid of a pig-tailed macaque (PNb) that developed AIDS. This virus (SHIVKU-1) is highly pathogenic when inoculated into other macaques. DNA sequence analysis of PCR-amplified products revealed a total of 5 nucleotide changes in the LTR while vif had 2 consensus amino acid changes. The gag, vif, and vpx had no consensus amino acid substitutions, whereas vpr had 1 consensus substitution. The tat and rev genes of the HXB2 region of SHIVKU-1 had 2 and 1 consensus amino acid changes, respectively. The vpu gene of the HXB2 region of SHIV, which originally had an ACG at the beginning of the gene, reverted to an initiation ATG codon and in addition contained a consensus amino acid substitution at position 69 of this protein. As expected, the majority of the nucleotide substitutions were found in the env and nef genes. Thirteen and 5 amino acid changes were predicted for the corresponding Env and Nef proteins, respectively. In addition, one-third of the env gene clones isolated from the SHIVKU-1 stock had a 5-amino-acid deletion in the V4 region. Using three independent assays, we determined that the changes in the SHIVKU-1 were associated with an increase in the efficiency of replication in macrophages. The strikingly few consensus changes in the virus suggest that conversion of this virus to one capable of causing AIDS in pig-tailed macaques was associated with relatively few changes in the viral envelope and/or accessory genes. These results will provide the basis for the development of a pathogenic, molecular clone of SHIV capable of causing AIDS in pig-tailed macaques.
authors.affiliation: Department of Microbiology, Molecular Genetics, and Immunology, Marion Merell Dow Laboratory for Viral Pathogenesis, University of Kansas Medical Center, Kansas City 66160-7240, USA.
authors.forename: E B
authors.initials: EB
authors.lastname: Stephens
authors.forename: S
authors.initials: S
authors.lastname: Mukherjee
authors.forename: M
authors.initials: M
authors.lastname: Sahni
authors.forename: W
authors.initials: W
authors.lastname: Zhuge
authors.forename: R
authors.initials: R
authors.lastname: Raghavan
authors.forename: D K
authors.initials: DK
authors.lastname: Singh
authors.forename: K
authors.initials: K
authors.lastname: Leung
authors.forename: B
authors.initials: B
authors.lastname: Atkinson
authors.forename: Z
authors.initials: Z
authors.lastname: Li
authors.forename: S V
authors.initials: SV
authors.lastname: Joag
authors.forename: Z Q
authors.initials: ZQ
authors.lastname: Liu
authors.forename: O
authors.initials: O
authors.lastname: Narayan
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000382:microbiology; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002678:Chimera; D003001:Cloning, Molecular; D005814:Genes, Viral; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity; D008254:Macaca nemestrina / Q000382:microbiology; D008264:Macrophages / Q000382:microbiology; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000382:microbiology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity; D013045:Species Specificity; D013601:T-Lymphocytes / Q000382:microbiology; D015678:Viral Structural Proteins / Q000235:genetics; D014779:Virus Replication
chemical_list: D015678:Viral Structural Proteins