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Journal of Virology, February 2009, p. 1422-1432, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02066-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

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

Nagadenahalli B. Siddappa,1,2 Ruijiang Song,1,2,{dagger} Victor G. Kramer,1 Agnès-Laurence Chenine,1,2 Vijayakumar Velu,5 Helena Ong,1 Robert A. Rasmussen,1,2 Ricky D. Grisson,1,2 Charles Wood,3 Hong Zhang,3 Chipeppo Kankasa,4 Rama Rao Amara,5,6 James G. Else,7 Francis J. Novembre,5,6 David C. Montefiori,8 and Ruth M. Ruprecht1,2*

Dana-Farber Cancer Institute,1 Harvard Medical School, Boston, Massachusetts 02115,2 Nebraska Center for Virology and School of Biological Sciences, University of Nebraska, Lincoln, Nebraska 68588,3 University Teaching Hospital, Lusaka, Zambia,4 Division of Microbiology and Immunology,5 Department of Microbiology and Immunology,6 Division of Animal Resources, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 30322,7 Department of Surgery, Duke University Medical Center, Durham, North Carolina 277108

Received 1 October 2008/ Accepted 7 November 2008

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.

* Corresponding author. Mailing address: Dana-Farber Cancer Institute, JFB809, 44 Binney Street, Boston, MA 02115. Phone: (617) 632-3719. Fax: (617) 632-3112. E-mail: ruth_ruprecht{at}dfci.harvard.edu

{triangledown} Published ahead of print on 19 November 2008.

{dagger} Present address: Aaron Diamond AIDS Research Center, New York, NY.

Journal of Virology, February 2009, p. 1422-1432, Vol. 83, No. 3
0022-538X/09/$08.00+0     doi:10.1128/JVI.02066-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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