Molecularly cloned SHIV-1157ipd3N4: a highly replication- competent, mucosally transmissible R5 simian-human immunodeficiency virus encoding HIV clade C Env
| Autor: | Helena Ong, C. M. McCann, Elizabeth Strobert, Weidong Xu, James G. Else, Robert A. Rasmussen, E. Shai-Kobiler, L. M. Goins, Ricky D. Grisson, Saied Mirshahidi, W. E. Secor, Harold M. McClure, Charles E. Wood, Claudia R. Ruprecht, Agnès-Laurence Chenine, P.-L. Li, Hong Zhang, James B. Whitney, Chipeppo Kankasa, Ruijiang Song, Tao Wang, Ruth M. Ruprecht |
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| Rok vydání: | 2006 |
| Předmět: |
Receptors
CXCR5 viruses Immunology Molecular Sequence Data Simian Acquired Immunodeficiency Syndrome HIV Infections Biology medicine.disease_cause Recombinant virus Virus Replication Microbiology Peripheral blood mononuclear cell Virus Serial passage Administration Rectal Virology medicine Animals Humans Amino Acid Sequence Cloning Molecular Receptors Cytokine Chimera virus diseases Gene Products env Infant Simian immunodeficiency virus AIDS Vaccines biology.organism_classification Macaca mulatta Long terminal repeat Insect Science Lentivirus HIV-1 Pathogenesis and Immunity Receptors Chemokine Simian Immunodeficiency Virus |
| Zdroj: | Journal of virology. 80(17) |
| ISSN: | 0022-538X |
| Popis: | 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 Cenvis 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 Cenv. 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-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. |
| Databáze: | OpenAIRE |
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