title: Characterisation of simian immunodeficiency virus-infected cells in pigtail macaques.
abstract: Defining which cells become infected with simian immunodeficiency virus (SIV) in vivo should assist in unravelling the pathogenesis of human immunodeficiency virus (HIV)/SIV infection. HIV/SIV infection of CD4(+) T cells resulted in down-regulation of CD3 and CD4 surface molecules in vitro, however this phenomenon is poorly characterised in vivo. Intracellular SIV p27 was studied by flow cytometry in serial blood samples and lymph node samples during acute infection of 17 SIVmac-infected pigtail macaques. Two weeks after infection, a mean of 56±6.8% the p27(+) cells were lymphocytes negative for surface CD4 and CD3, and indeed the highest proportion of SIV infected cells were found in the small subset of CD3(Lo)CD4(-)CD8(-) lymphocytes, indicating that infection has lead to down-regulation of these markers in vivo. Furthermore, the relative amount of SIV p27 within lymphocytes (based of mean fluorescence intensity) was higher in CD3(Lo)CD4(-) and CD3(-) infected cells than in CD3(+) or CD4(+) p27(+) populations, consistent with greater viral production in CD4(+) T cells down-regulating CD3 and CD4 molecules. The CD3(-)CD4(-) infected cells expressed T cell markers CD2 and CD5 and were negative for monocyte, NK and B cell markers. The majority of infected cells were CD28(+)CD95(+) central memory T cells. Surprisingly, p27(+) blood lymphocytes were mostly negative for activation markers CD25 and CD69, but most of the infected lymph nodes cells were activated. Our results characterise productively-infected macaque lymphocytes in vivo. The high proportion of SIV-infected lymphocytes that are CD3(-)CD4(-) has important implications for the in vivo study of pathogenesis of SIV/HIV infections.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Royal Parade, Parkville, 3010 VIC, Australia. wwinnall@unimelb.edu.au
authors.forename: Wendy R
authors.initials: WR
authors.lastname: Winnall
authors.forename: Amy
authors.initials: A
authors.lastname: Sexton
authors.forename: Sheilajen
authors.initials: S
authors.lastname: Alcantara
authors.forename: Sarah
authors.initials: S
authors.lastname: Roath
authors.forename: Robert
authors.initials: R
authors.lastname: De Rose
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kent
mesh_terms: D000818:Animals; D017252:CD3 Complex / Q000235:genetics / Q000276:immunology; D015704:CD4 Antigens / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D015536:Down-Regulation; D015658:HIV Infections / Q000235:genetics / Q000276:immunology* / Q000821:virology; D006801:Humans; D008254:Macaca nemestrina; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D017252:CD3 Complex; D015704:CD4 Antigens; D014764:Viral Proteins