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A pathogenic R5 simian-human immunodeficiency virus (SHIV) encoding HIV clade C<jats:italic>env<\/jats:italic>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<jats:italic>env<\/jats:italic>. SHIV-1157i was adapted by serial passage in five monkeys, three of which developed peripheral CD4<jats:sup>+<\/jats:sup>T-cell depletion. After the first inoculated monkey developed AIDS at week 137 postinoculation, transfer of its infected blood to a nai\u0308ve 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-\u03baB binding site was engineered into its 3\u2032 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.<\/jats:p>","DOI":"10.1128\/jvi.00558-06","type":"journal-article","created":{"date-parts":[[2006,8,15]],"date-time":"2006-08-15T22:42:56Z","timestamp":1155681776000},"page":"8729-8738","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":141,"title":["Molecularly Cloned SHIV-1157ipd3N4: a Highly Replication- Competent, Mucosally Transmissible R5 Simian-Human Immunodeficiency Virus Encoding HIV Clade C<i>env<\/i>"],"prefix":"10.1128","volume":"80","author":[{"given":"R. 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