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

Authors

• R. J. Song, Harvard Medical School
• A.-L. Chenine, Harvard Medical School
• R. A. Rasmussen, Harvard Medical School
• C. R. Ruprecht, Dana-Farber Cancer Institute, Boston, Massachusetts
• S. Mirshahidi, Dana-Farber Cancer Institute, Boston, Massachusetts
• D. R. Grisson, Dana-Farber Cancer Institute, Boston, Massachusetts
• W. Xu, Dana-Farber Cancer Institute, Boston, Massachusetts
• J. B. Whitney, Dana-Farber Cancer Institute, Boston, Massachusetts
• L. M. Goins, Dana-Farber Cancer Institute, Boston, Massachusetts
• H. Ong, Dana-Farber Cancer Institute, Boston, Massachusetts
• P.-L. Li, Dana-Farber Cancer Institute, Boston, Massachusetts
• E. Shai-Kobiler, Dana-Farber Cancer Institute, Boston, Massachusetts
• T. Wang, Dana-Farber Cancer Institute, Boston, Massachusetts
• C. M. McCann, Dana-Farber Cancer Institute, Boston, Massachusetts
• Hong Zhang, Univesity of Nebraska - LincolnFollow
• Charles Wood, University of Nebraska-LincolnFollow
• C. Kankasa, University Teaching Hospital, Lusaka, Zambia
• W. E. Secor, Division of Parasitic Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia
• H. M. McClure, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia
• E. Strobert, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia
• J. G. Else, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia
• R. M. Ruprecht, Harvard Medical School

Document Type

Article

Date of this Version

9-2006

Comments

Published in JOURNAL OF VIROLOGY, Sept. 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. Used by permission.

Abstract

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 Cenv 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^{4 T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a naı¨ve 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-κB 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.}