title: Simian immunodeficiency virus SIVmac239 infection and simian human immunodeficiency virus SHIV89.6P infection result in progression to AIDS in cynomolgus macaques of Asian origin.
abstract: Simian immunodeficiency virus (SIV) infection models in cynomolgus macaques are important for analysis of the pathogenesis of immunodeficiency virus and for studies on the efficacy of new vaccine candidates. However, very little is known about the pathogenesis of SIV or simian human immunodeficiency virus (SHIV) in cynomolgus macaques from different Asian countries. In the present study, we analysed the infectivity and pathogenicity of CCR5-tropic SIVmac and those of dual-tropic SHIV89.6P inoculated into cynomolgus macaques in Indonesian, Malaysian or Philippine origin. The plasma viral loads in macaques infected with either SIVmac239 or SHIV89.6P were maintained at high levels. CD4+ T cell levels in macaques infected with SIVmac239 gradually decreased. All of the macaques infected with SHIV89.6P showed greatly reduced CD4+ T-cell numbers within 6 weeks of infection. Eight of the 11 macaques infected with SIVmac239 were killed due to AIDS symptoms after 2-4.5 years, while four of the five macaques infected with SHIV89.6P were killed due to AIDS symptoms after 1-3.5 years. We also analysed cynomolgus macaques infected intrarectally with repeated low, medium or high doses of SIVmac239, SIVmac251 or SHIV89.6P. Infection was confirmed by quantitative RT-PCR at more than 5000, 300 and 500 TCID50 for SIVmac239, SIVmac251 and SHIV89.6P, respectively. The present study indicates that cynomolgus macaques of Asian origin are highly susceptible to SIVmac and SHIV infection by both intravenous and mucosal routes. These models will be useful for studies on virus pathogenesis, vaccination and therapeutics against human immunodeficiency virus/AIDS.
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Okamura
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsujimura
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan.|Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Shogo
authors.initials: S
authors.lastname: Soma
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takahashi
authors.affiliation: Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo 204-0022, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Tsukuba, Ibaraki 305-0843, Japan.|Division of Immunoregulation, Department of Molecular and Experimental Medicine, Mie University Graduate School of Medicine, Tsu, Mie 514-8507, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000473:pathology / Q000821:virology*; D000818:Animals; D001208:Asia; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D006678:HIV / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000502:physiology*; D019562:Viral Load