title: Simian-Human immunodeficiency viruses expressing chimeric subtype B/C Vpu proteins demonstrate the importance of the amino terminal and transmembrane domains in the rate of CD4(+) T cell loss in macaques.
abstract: Previously, we reported that simian-human immunodeficiency viruses expressing either the lab adapted subtype B (SHIV(KU-1bMC33)) or subtype C (SHIV(SCVpu)) Vpu proteins of human immunodeficiency virus type 1 (HIV-1) had different rates of CD4(+) T cell loss following inoculation into macaques. In this study, we have generated SHIVs that express either the subtype B or subtype C N-terminal (NTD) and transmembrane (TMD) domains and the opposing cytoplasmic domain (SHIV(VpuBC), SHIV(VpuCB)). In culture systems, SHIV(VpuBC) replicated faster than SHIV(VpuCB) while both proteins exhibited similar ability to down-modulate CD4 surface expression. Following inoculation into macaques, SHIV(VpuBC) resulted in rapid CD4(+) T cell loss similar to the parental SHIV(KU-1bMC33), while the rate of CD4(+) T cell loss in those inoculated with SHIV(VpuCB) was intermediate of SHIV(SCVpu) and SHIV(KU-1bMC33). These results emphasize the importance of the Vpu NTD/TMD region in the rate of CD4(+) T cell loss in the pathogenic X4 SHIV/macaque model.
authors.affiliation: Department of Microbiology, Molecular Genetics, and Immunology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
authors.forename: Autumn
authors.initials: A
authors.lastname: Ruiz
authors.forename: Kimberly
authors.initials: K
authors.lastname: Schmitt
authors.forename: Nathan
authors.initials: N
authors.lastname: Culley
authors.forename: Edward B
authors.initials: EB
authors.lastname: Stephens
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology; D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000473:pathology*; D002460:Cell Line; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D054298:Human Immunodeficiency Virus Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008254:Macaca nemestrina; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000473:pathology / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000145:classification / Q000235:genetics / Q000378:metabolism / Q000472:pathogenicity*; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000086082:Viroporin Proteins
chemical_list: D049452:Green Fluorescent Proteins; D054298:Human Immunodeficiency Virus Proteins; D011993:Recombinant Fusion Proteins; D054334:Viral Regulatory and Accessory Proteins; C485184:enhanced green fluorescent protein; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins