title: CD4+ lymphocytopenia in acute infection of Asian macaques by a vaginally transmissible subtype-C, CCR5-tropic Simian/Human Immunodeficiency Virus (SHIV).
abstract: An R5-tropic SHIV(CHN19P4) was previously generated using a primary HIV-1 subtype-C envelope. We have further characterized this SHIV in two species of macaques. To determine whether this isolate is transmissible vaginally, female pig-tailed macaques were inoculated with 2 x 10(3) TCID50 of SHIV(CHN19P4) by the vaginal route. Animals became infected with a high peak plasma viremia (>10(7) viral copies/mL) and rapid seroconversion. The viremia was accompanied by CD4+ lymphocytopenia in the gut lamina propria lymphocyte (LPL) population. Comparable CD4+ T-cell loss was not seen in peripheral blood and colonic lymph nodes. These findings demonstrate a unique R5-tropic SHIV that can be used to study envelope-related issues in vaginal transmission of the most prevalent subtype of HIV-1. We also found that rhesus macaques intravenously inoculated with 1 x 10(3) TCID50 of SHIV(CHN19P4) became infected and showed CD4+ lymphocytopenia in the gut LPL population. Despite inactivation of the vpu gene in SHIV(CHN19P4), the virus appears to target mainly gut-associated lymphoid tissues during the initial stage of infection as has been described for SHIV(SF162P), another R5-tropic (subtype B) recombinant virus. Our data indicate that the R5-mediated CD4+ lymphocytopenia in the gut is likely independent of HIV-1 genotypes and of the function of vpu at the acute phase of viral infection.
authors.affiliation: Aaron Diamond AIDS Research Center, The Rockefeller University, New York, New York 10016, USA.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiuqing
authors.initials: X
authors.lastname: Zhao
authors.forename: Yaoxing
authors.initials: Y
authors.lastname: Huang
authors.forename: Agegnehu
authors.initials: A
authors.lastname: Gettie
authors.forename: Lei
authors.initials: L
authors.lastname: Ba
authors.forename: James
authors.initials: J
authors.lastname: Blanchard
authors.forename: David D
authors.initials: DD
authors.lastname: Ho
mesh_terms: D000208:Acute Disease; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D015752:Genes, env; D016338:Genes, vpu; D015658:HIV Infections / Q000276:immunology / Q000503:physiopathology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D008231:Lymphopenia / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008969:Molecular Sequence Data; D019713:Receptors, CCR5 / Q000378:metabolism; D017422:Sequence Analysis, DNA; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000503:physiopathology / Q000635:transmission / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000378:metabolism / Q000472:pathogenicity*; D014621:Vagina / Q000821:virology*
chemical_list: D019713:Receptors, CCR5