Neutralization-Sensitive R5-Tropic Simian-Human Immunodeficiency Virus SHIV-2873Nip, Which Carries env Isolated from an Infant with a Recent HIV Clade C Infection

被引:35
|
作者
Siddappa, Nagadenahalli B. [1 ,2 ]
Song, Ruijiang [1 ,2 ]
Kramer, Victor G. [1 ]
Chenine, Agnes-Laurence [1 ,2 ]
Velu, Vijayakumar [6 ]
Ong, Helena [1 ]
Rasmussen, Robert A. [1 ,2 ]
Grisson, Ricky D. [1 ,2 ]
Wood, Charles [3 ,4 ]
Zhang, Hong [3 ,4 ]
Kankasa, Chipeppo [5 ]
Amara, Rama Rao [6 ,7 ]
Else, James G. [8 ]
Novembre, Francis J. [6 ,7 ]
Montefiori, David C. [9 ]
Ruprecht, Ruth M. [1 ,2 ]
机构
[1] Dana Farber Canc Inst, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Boston, MA 02115 USA
[3] Univ Nebraska, Nebraska Ctr Virol, Lincoln, NE 68588 USA
[4] Univ Nebraska, Sch Biol Sci, Lincoln, NE 68588 USA
[5] Univ Teaching Hosp, Lusaka, Zambia
[6] Emory Univ, Yerkes Natl Primate Res Ctr, Div Microbiol & Immunol, Atlanta, GA 30322 USA
[7] Emory Univ, Yerkes Natl Primate Res Ctr, Dept Microbiol & Immunol, Atlanta, GA 30322 USA
[8] Emory Univ, Yerkes Natl Primate Res Ctr, Div Anim Resources, Atlanta, GA 30322 USA
[9] Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA
基金
美国国家卫生研究院;
关键词
T-CELL DEPLETION; HUMAN MONOCLONAL-ANTIBODY; PROXIMAL EXTERNAL REGION; PIG-TAILED MACAQUES; TYPE-1; SUBTYPE-C; RHESUS MACAQUES; DISEASE PROGRESSION; IN-VITRO; GASTROINTESTINAL-TRACT; PERSISTENT INFECTION;
D O I
10.1128/JVI.02066-08
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Human immunodeficiency virus clade C (HIV-C) accounts for >56% of all HIV infections worldwide. To investigate vaccine safety and efficacy in nonhuman primates, a pathogenic, R5-tropic, neutralization-sensitive simian-human immunodeficiency virus (SHIV) carrying HIV-C env would be desirable. We have constructed SHIV-2873Ni, an R5-tropic SHIV carrying a primary pediatric HIV-C env gene isolated from a 2-month-old Zambian infant, who died within 1 year of birth. SHIV-2873Ni was constructed using SHIV-1157ipd3N4 ( R. J. Song, A. L. Chenine, R. A. Rasmussen, C. R. Ruprecht, S. Mirshahidi, R. D. Grisson, W. Xu, J. B. Whitney, L. M. Goins, H. Ong, P. L. Li, E. Shai-Kobiler, T. Wang, C. M. McCann, H. Zhang, C. Wood, C. Kankasa, W. E. Secor, H. M. McClure, E. Strobert, J. G. Else, and R. M. Ruprecht. J. Virol. 80: 8729-8738, 2006) as the backbone, since the latter contains additional NF-kappa B sites in the long terminal repeats to enhance viral replicative capacity. The parental virus, SHIV-2873Ni, was serially passaged through five rhesus monkeys (RMs); SHIV-2873Nip, the resulting passaged virus, was reisolated from the fourth recipient about 1 year postinoculation. SHIV-2873Nip was replication competent in RM peripheral blood mononuclear cells of all random donors tested and was exclusively R5 tropic, and its env gene clustered with HIV-C by phylogenetic analysis; its high sensitivity to neutralization led to classification as a tier 1 virus. Indian-origin RMs were inoculated by different mucosal routes, resulting in high peak viral RNA loads. Signs of virus-induced disease include depletion of gut CD4(+) T lymphocytes, loss of memory T cells in blood, and thrombocytopenia that resulted in fatal cerebral hemorrhage. SHIV-2873Nip is a highly replication-competent, mucosally transmissible, pathogenic R5-tropic virus that will be useful to study viral pathogenesis and to assess the efficacy of immunogens targeting HIV-C Env.
引用
收藏
页码:1422 / 1432
页数:11
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