JVI Accepts, published online ahead of print on 21 May 2008

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J. Virol. doi:10.1128/JVI.01003-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Vpx is critical for the reverse transcription of human immunodeficiency virus type 2 genome in macrophages

Mikako Fujita, Masami Otsuka, Masami Miyoshi, Boonruang Khamsri, Masako Nomaguchi, and Akio Adachi^*

Department of Bioorganic Medicinal Chemistry, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan; Department of Virology, Institute of Health Biosciences, The University of Tokushima Graduate School, Tokushima 770-8503, Japan

^* To whom correspondence should be addressed. Email: adachi{at}basic.med.tokushima-u.ac.jp.

The ability of wild-type and vpx-minus human immunodeficiency virus type 2 (HIV-2) clones to synthesize viral DNA in human monocyte-derived macrophages (MDMs) and lymphocytic cells was comparatively and quantitatively evaluated. While the vpx-minus mutant directed the synthesis of viral DNA comparably and normally with wild-type virus in lymphocytic cells, no appreciable viral DNA was detected in MDMs infected with the mutant. To substantiate this finding and to determine whether there is some specific region(s) in Vpx crucial for viral DNA synthesis in MDMs, we have generated a series of site-specific point mutants of vpx and examined their phenotypes. The resultant five mutants with no infectivity for MDMs again showed, without exceptions, the same defect with the vpx-minus mutant. Our results here clearly demonstrated that the entire Vpx is critical for the reverse transcription of HIV-2 genome in human MDMs.

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