Abstract
The human immunodeficiency virus-1 (HIV-1) Vpr protein plays multiple roles in HIV-1 replication. In early infection, Vpr provides help in the nuclear localization of pre-integration complex. Subsequently, Vpr induces cell cycle arrest of infected cells at G2/M phase. Cell cycle arrest facilitates higher rate of viral gene transcription. Vpr is also capable of activating transcription of viral and heterologous genes. Vpr induces apoptosis in infected cells leading to loss of immune cells and onset of clinical AIDS. Interestingly, Vpr is also considered as a passenger protein in the virus particles as it is incorporated into the virus particles through interaction with Gag. The structure of full length Vpr has been resolved recently through NMR. In this review, we have analysed the functions of Vpr using the available data from structural perspective. Packing of the three helices of Vpr around a core formed by hydrophobic side chains and integrity of helical domains are critical for Vpr functions. The distinct functions of Vpr have been attributed to structural integrity of different domains. The unique distribution of acidic and basic residues in Vpr is an interesting feature. Two hydrophobic pockets on the structure of Vpr are proposed to be important targets for modulating Vpr functions. The inter-relationship between different functions of Vpr is discussed in the context of structure. Based on bioinformatics analysis, we propose new targets for modulating Vpr functions, which need to be validated experimentally.
Keywords: HIV-1 Vpr, gene transcription, apoptosis, hydrophobic pockets, Acquired immunodeficiency syndrome (AIDS)
Current HIV Research
Title: HIV-1 Vpr: A Closer Look at the Multifunctional Protein from the Structural Perspective
Volume: 7 Issue: 2
Author(s): Ramesh C. Pandey, Debduti Datta, Ruma Mukerjee, Alagarsamy Srinivasan, Sundarasamy Mahalingam and Bassel E. Sawaya
Affiliation:
Keywords: HIV-1 Vpr, gene transcription, apoptosis, hydrophobic pockets, Acquired immunodeficiency syndrome (AIDS)
Abstract: The human immunodeficiency virus-1 (HIV-1) Vpr protein plays multiple roles in HIV-1 replication. In early infection, Vpr provides help in the nuclear localization of pre-integration complex. Subsequently, Vpr induces cell cycle arrest of infected cells at G2/M phase. Cell cycle arrest facilitates higher rate of viral gene transcription. Vpr is also capable of activating transcription of viral and heterologous genes. Vpr induces apoptosis in infected cells leading to loss of immune cells and onset of clinical AIDS. Interestingly, Vpr is also considered as a passenger protein in the virus particles as it is incorporated into the virus particles through interaction with Gag. The structure of full length Vpr has been resolved recently through NMR. In this review, we have analysed the functions of Vpr using the available data from structural perspective. Packing of the three helices of Vpr around a core formed by hydrophobic side chains and integrity of helical domains are critical for Vpr functions. The distinct functions of Vpr have been attributed to structural integrity of different domains. The unique distribution of acidic and basic residues in Vpr is an interesting feature. Two hydrophobic pockets on the structure of Vpr are proposed to be important targets for modulating Vpr functions. The inter-relationship between different functions of Vpr is discussed in the context of structure. Based on bioinformatics analysis, we propose new targets for modulating Vpr functions, which need to be validated experimentally.
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Cite this article as:
Pandey C. Ramesh, Datta Debduti, Mukerjee Ruma, Srinivasan Alagarsamy, Mahalingam Sundarasamy and Sawaya E. Bassel, HIV-1 Vpr: A Closer Look at the Multifunctional Protein from the Structural Perspective, Current HIV Research 2009; 7 (2) . https://dx.doi.org/10.2174/157016209787581508
DOI https://dx.doi.org/10.2174/157016209787581508 |
Print ISSN 1570-162X |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4251 |
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