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Construction and in vivo infection of a new simian/human immunodeficiency virus chimera containing the reverse transcriptase gene and the 3' half of the genomic region of human immunodeficiency virus type 1

Institute for Virus Research, Laboratory of Viral Pathogenesis, Kyoto University, 53 Shogoin-kawaharacho, Sakyo-ku, Kyoto 606-8507, Japan

Correspondence
Eiji Ido
eido{at}virus.kyoto-u.ac.jp

A new simian/human immunodeficiency virus (SHIV) chimera with the reverse transcriptase (RT)-encoding region of pol, in addition to the 3' region encoding vpr, vpu, tat, rev, env and nef of HIV-1, on an SIV_mac (SIV from a macaque monkey) background was constructed. This new SHIV chimera, named SHIVrt/3rn, could replicate in monkey peripheral blood mononuclear cells (PBMCs) as well as in the human and monkey CD4⁺ T-cell lines M8166 and HSC-F. Since SHIVrt/3rn contains the RT gene of HIV-1, replication of the virus in M8166 cells was inhibited by an HIV-1-specific non-nucleoside RT inhibitor, MKC-442, with a sensitivity similar to that of HIV-1. To investigate the replication competence of SHIVrt/3rn in vivo, two rhesus monkeys were inoculated intravenously with the virus. At 2 to 4 weeks post-inoculation (p.i.), plasma viral RNA loads of both monkeys showed a peak value of more than 10⁴ copies ml^-1. Infectious virus was isolated from the PBMCs of one monkey at 2 and 3 weeks p.i. and from the other at 4 weeks p.i. Moreover, proviral DNA was detected constantly throughout the observation period, starting from 3 weeks p.i. An antibody response, detected first at 3 weeks p.i., was maintained at high titres. These results indicate that SHIVrt/3rn can infect and replicate in vivo. SHIVrt/3rn, having part of HIV-1 pol in addition to the 3' part of the HIV-1 genome is genetically more close to HIV-1 than any of the other monkey-infecting SHIVs reported previously.

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