title: High immune activation and abnormal expression of cytokines contribute to death of SHIV89.6-infected Chinese rhesus macaques.
abstract: Chinese rhesus macaques (CRMs) are ideal experimental animals for studying the pathogenesis of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) and for vaccine research. SHIV89.6 has been reported to be an attenuated virus because, in most cases, SHIV89.6 infection only causes limited alteration of immune cells and tissues, and it has been used commonly for vaccine research. After two serial passages in vivo, SHIV (SHIV-89.6P) induces CD4 lymphopenia and an AIDS-like disease with wasting and opportunistic infections. However, the pathogenic ability of SHIV89.6 is not well understood. In this study, we found that 6 of 14 SHIV89.6-infected CRMs died within 127 weeks after infection. We found especially high immune activation, low IFN-α expression, and distinctive cytokine expression profiles in the infected and dead (ID) group of monkeys, while there was only few change in the CD4(+) T counts and distribution of T cell subsets in the ID group monkeys. Also, there was a similar dynamic of viral load between infected and surviving (IS) and ID group monkeys. Furthermore, we found various correlations among immune activation, IFN-α expression, and frequencies of cytokine-secreting cells. These results suggest that SHIV89.6 infections have pathogenic potential in CRMs and that high immune activation and abnormal expression of cytokines contribute to death of SHIV89.6-infected CRMs. This also implies that high immune activation may be relevant to dysfunction of immune cells. It is proposed that high immune activation and dysfunction of immune cells may be good predictors for disease progression and markers for therapy.
authors.affiliation: Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, Yunnan, China.
authors.forename: Ren-Rong
authors.initials: RR
authors.lastname: Tian
authors.forename: Ming-Xu
authors.initials: MX
authors.lastname: Zhang
authors.forename: Lin-Tao
authors.initials: LT
authors.lastname: Zhang
authors.forename: Xiao-Liang
authors.initials: XL
authors.lastname: Zhang
authors.forename: Hong-Yi
authors.initials: HY
authors.lastname: Zheng
authors.forename: Lin
authors.initials: L
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Pang
authors.forename: Gao-Hong
authors.initials: GH
authors.lastname: Zhang
authors.forename: Yong-Tang
authors.initials: YT
authors.lastname: Zheng
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D016898:Interferon-alpha / Q000235:genetics / Q000276:immunology; D008253:Macaca mulatta / Q000276:immunology / Q000821:virology; D008297:Male; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics / Q000276:immunology* / Q000401:mortality / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology*
chemical_list: D016207:Cytokines; D016898:Interferon-alpha