Vpu: a multifunctional protein that enhances the pathogenesis of human immunodeficiency virus type 1.
The Vpu protein is the smallest of the proteins encoded by human immunodeficiency virus type 1 (HIV-1). This transmembrane protein interacts with the CD4 molecule in the rough endoplasmic reticulum (RER), resulting in its degradation via the proteasome pathway. Vpu also has been shown to enhance virion release from infected cells. While much has been learned about the function of Vpu in cell culture systems, its exact role in HIV-1 pathogenesis is still unknown. This has been primarily due to the lack of a suitable primate model system since vpu is found only in HIV-1 and simian immunodeficiency viruses isolated from chimpanzees (SIVcpz), and three species of old world monkeys within the genus Cercopithecus. Several laboratories have developed pathogenic molecular clones of simian-human immunodeficiency virus (SHIV) in which the tat, rev, vpu and env genes of HIV-1 are expressed in the genetic background of SIV. The availability of such clones has allowed investigators to assess the role of Vpu in pathogenesis using a relevant animal model. This review will focus on the current understanding of the structure-function relationships of Vpu protein and recent advances using the SHIV model to assess the role of Vpu in HIV-1 pathogenesis.
Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. estephen@kumc.edu
David R
DR
Hout
Ellyn R
ER
Mulcahy
Erik
E
Pacyniak
Lisa M
LM
Gomez
Melissa L
ML
Gomez
Edward B
EB
Stephens
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015704:CD4 Antigens / Q000276:immunology; D002462:Cell Membrane / Q000821:virology; D004195:Disease Models, Animal; D016338:Genes, vpu / Q000502:physiology*; D015658:HIV Infections / Q000821:virology*; D015497:HIV-1 / Q000472:pathogenicity* / Q000502:physiology; D054298:Human Immunodeficiency Virus Proteins; D006801:Humans; D008251:Macaca; D008969:Molecular Sequence Data; D016865:Reassortant Viruses; D016415:Sequence Alignment; D016097:Simian Acquired Immunodeficiency Syndrome / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics; D054334:Viral Regulatory and Accessory Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014774:Virulence; D014779:Virus Replication; D000086082:Viroporin Proteins
D015704:CD4 Antigens; D054298:Human Immunodeficiency Virus Proteins; D054334:Viral Regulatory and Accessory Proteins; C514859:vpu protein, Human immunodeficiency virus 1; D000086082:Viroporin Proteins