title: A highly pathogenic simian/human immunodeficiency virus with genetic changes in cynomolgus monkey.
abstract: A highly pathogenic simian/human immunodeficiency virus (SHIV), designated C2/1, was obtained by serum passages in cynomolgus monkeys of p-SHIV, an SHIV strain that contains the env gene of pathogenic human immunodeficiency virus type 1 89.6. CD4+ lymphocyte depletion was induced within 1 week of the SHIV-C2/1 infection in peripheral blood as well as in various lymphoid organs in all the animals tested, with symptoms of diarrhoea and no increase in body weight, followed by intense viraemia. Serum antibody against Env protein was detected from 4 weeks after the virus infection, while the anti-Gag antibody response was absent in the SHIV-C2/1-infected animals. In contrast, both anti-Gag and anti-Env antibody responses were present in animals infected with p-SHIV or the non-pathogenic SHIV-MN. Sequencing of the env gene of isolates of SHIV-C strains showed conserved amino acid changes in the Env C2 and V3 regions that included changes to negatively charged amino acids, in the cytoplasmic region of gp41 that included a 42 amino acid deletion, and in the Nef protein. The pathogenic SHIV-C2/1-monkey model suggests that virus-specific pathogenicity in SHIV infection may be associated with the absence of anti-Gag antibody responses in animals and may be caused by genetic changes during serum passage in vivo.
authors.forename: K
authors.initials: K
authors.lastname: Shinohara
authors.forename: K
authors.initials: K
authors.lastname: Sakai
authors.forename: S
authors.initials: S
authors.lastname: Ando
authors.forename: Y
authors.initials: Y
authors.lastname: Ami
authors.forename: N
authors.initials: N
authors.lastname: Yoshino
authors.forename: E
authors.initials: E
authors.lastname: Takahashi
authors.forename: K
authors.initials: K
authors.lastname: Someya
authors.forename: Y
authors.initials: Y
authors.lastname: Suzaki
authors.forename: T
authors.initials: T
authors.lastname: Nakasone
authors.forename: Y
authors.initials: Y
authors.lastname: Sasaki
authors.forename: M
authors.initials: M
authors.lastname: Kaizu
authors.forename: Y
authors.initials: Y
authors.lastname: Lu
authors.forename: M
authors.initials: M
authors.lastname: Honda
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D018791:CD4 Lymphocyte Count; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics; D015754:Genes, nef; D006678:HIV / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity*; D015483:HIV Antibodies / Q000097:blood; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000737:chemistry / Q000235:genetics; D006801:Humans; D008252:Macaca fascicularis; D008969:Molecular Sequence Data; D012692:Serial Passage; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D015700:HIV Envelope Protein gp41; D054311:nef Gene Products, Human Immunodeficiency Virus