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Partner molecules of accessory protein Vpr of the human immunodeficiency virus type 1

Tomoshige Kino1, George N Pavlakis

  • 1Human Retrovirus Section, Center for Basic Research, National Cancer Institute-Frederick, Frederick, Maryland 21702-1201, USA.

DNA and Cell Biology
|May 15, 2004
PubMed

Insights

The Viral protein-R (Vpr) of Human Immunodeficiency Virus type-1 is a key regulatory molecule influencing viral replication and host cell functions. Its diverse activities, mediated by distinct molecular domains, interact with various host and viral proteins, necessitating further research.

Area of Science:

  • Virology
  • Molecular Biology
  • Immunology

Background:

  • The Human Immunodeficiency Virus type-1 (HIV-1) contains a virion-associated protein known as Viral protein-R (Vpr).
  • Vpr is conserved across HIV-1, HIV-2, and Simian Immunodeficiency Virus (SIV), indicating its critical role in lentiviral biology.
  • Vpr is known to enter the host cell nucleus and modulate viral replication and host cell functions.

Purpose of the Study:

  • To elucidate the multifaceted functions of the HIV-1 Vpr protein.
  • To understand how Vpr's distinct molecular domains contribute to its various activities.
  • To identify host and viral interactors associated with specific Vpr domains.

Main Methods:

  • Analysis of Vpr protein structure-function relationships.
  • Identification of host and viral proteins interacting with different Vpr domains.
  • Assessment of Vpr's impact on viral replication and host cell cycle progression.

Main Results:

  • Vpr exhibits diverse activities including promoter activation, G2/M cell cycle arrest, and apoptosis induction.
  • Specific Vpr domains mediate distinct functions: N-terminal for packaging, C-terminal for cell cycle arrest, and central alpha-helices for transcriptional activation and apoptosis.
  • Vpr interacts with host factors like transcription factors, coactivators, and apoptotic proteins, as well as viral Gag and cyclophilin A.

Conclusions:

  • Vpr is a crucial early regulatory protein in HIV and other lentiviruses.
  • The distinct functional domains of Vpr mediate interactions with specific cellular and viral partners.
  • Further investigation into Vpr's functions and interactions is essential for a comprehensive understanding of lentiviral pathogenesis.

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