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Journal of Virology, September 2006, p. 8729-8738, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00558-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade C env

R. J. Song,1,2 A.-L. Chenine,1,2 R. A. Rasmussen,1,2 C. R. Ruprecht,1 S. Mirshahidi,1,2 R. D. Grisson,1,2 W. Xu,1,2 J. B. Whitney,1,2 L. M. Goins,1,2 H. Ong,1 P.-L. Li,1,2 E. Shai-Kobiler,1,2 T. Wang,1,2 C. M. McCann,1,2 H. Zhang,3 C. Wood,3 C. Kankasa,4 W. E. Secor,5 H. M. McClure,6 E. Strobert,6 J. G. Else,6 and R. M. Ruprecht1,2*

Dana-Farber Cancer Institute, Boston, Massachusetts 02115,1 Harvard Medical School, Boston, Massachusetts 02115,2 Nebraska Center for Virology and School of Biological Science, University of Nebraska, Lincoln, Nebraska 68588,3 University Teaching Hospital, Lusaka, Zambia,4 Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30341,5 Yerkes National Primate Research Center, Emory University, Atlanta, Georgia 303226

Received 16 March 2006/ Accepted 16 June 2006

Human immunodeficiency virus type 1 (HIV-1) clade C causes >50% of all HIV infections worldwide, and an estimated 90% of all transmissions occur mucosally with R5 strains. A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C env is highly desirable to evaluate candidate AIDS vaccines in nonhuman primates. To this end, we generated SHIV-1157i, a molecular clone from a Zambian infant isolate that carries HIV clade C env. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4+ T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naïve animal induced memory T-cell depletion and thrombocytopenia within 3 months in the recipient. In parallel, genomic DNA from the blood donor was amplified to generate the late proviral clone SHIV-1157ipd3. To increase the replicative capacity of SHIV-1157ipd3, an extra NF-{kappa}B binding site was engineered into its 3' long terminal repeat, giving rise to SHIV-1157ipd3N4. This virus was exclusively R5 tropic and replicated more potently in rhesus peripheral blood mononuclear cells than SHIV-1157ipd3 in the presence of tumor necrosis factor alpha. Rhesus macaques of Indian and Chinese origin were next inoculated intrarectally with SHIV-1157ipd3N4; this virus replicated vigorously in both sets of monkeys. We conclude that SHIV-1157ipd3N4 is a highly replication-competent, mucosally transmissible R5 SHIV that represents a valuable tool to test candidate AIDS vaccines targeting HIV-1 clade C Env.

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

Journal of Virology, September 2006, p. 8729-8738, Vol. 80, No. 17
0022-538X/06/$08.00+0     doi:10.1128/JVI.00558-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



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