Human Immunodeficiency Virus Type 1 Vpr Is a Positive Regulator of Viral Transcription and Infectivity in Primary Human Macrophages

Journal of Experimental Medicine - Tập 187 Số 7 - Trang 1103-1111 - 1998
Ramu A. Subbramanian1, Allégria Kessous-Elbaz1, Robert Lodge1, J. Forget1, Xiaojian Yao1, Dominique Bergeron1, Éric A. Cohen1
1From the *Laboratory of Human Retrovirology, Department of Microbiology and Immunology, and the ‡Department of Pathology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada H3C3J7

Tóm tắt

It is currently well established that HIV-1 Vpr augments viral replication in primary human macrophages. In its virion-associated form, Vpr has been suggested to aid efficient translocation of the proviral DNA into the cell nucleus. Although Vpr growth-arrests dividing T cells, the relevance of this biological activity in nondividing macrophages is unclear. Here we use Vpr-mutants to demonstrate that the molecular determinants involved in G2-arresting T cells are also involved in increasing viral transcription in macrophages, even though these cells are refractive to the diploid DNA status typical of G2 phase. Our results suggest that the two phenotypes, namely the nuclear localization and the G2-arrest activity of the protein, segregate functionally among the late and early functions of Vpr. The nuclear localization property of Vpr correlates with its ability to effectively target the proviral DNA to the cell nucleus early in the infection, whereas the G2-arrest phenotype correlates with its ability to activate viral transcription after establishment of an infection. These two functions may render Vpr's role essential and not accessory under infection conditions that closely mimic the in vivo situation, that is, primary cells being infected at low viral inputs.

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Journal of Experimental Medicine

Tập 187 Số 7

1103-1111

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