HIV1-viral protein R (Vpr) mutations: associated phenotypes and relevance for clinical pathologies.
Over the last 30 years, research into HIV has advanced the knowledge of virus genetics and the development of efficient therapeutic strategies. HIV-1 viral protein R (Vpr) is a specialized and multifunctional protein that plays important roles at multiple stages of the HIV-1 viral life cycle. This protein interacts with a number of cellular and viral proteins and with multiple activities including nuclear transport of the pre-integration complex (PIC) to the nucleus, transcriptional activation, cell cycle arrest at G2/M transition phase and induction of cell death via apoptosis. Specifically, Vpr has been shown to control many host cell functions through a variety of biological processes and by interaction with several cellular pathways. The different functions of Vpr may enhance viral replication and impair the immune system in HIV-1 infected patients. Importantly, functional defects induced by mutations in the Vpr protein correlate with slow disease progression of HIV-infected patients. Vpr is also associated with other concomitant pathologies developed by these patients, which may lead it to be considered as a potential novel therapeutic target. This review will focus on HIV-1 Vpr, mainly on the importance of its structural mutations on the progression of HIV infection, associated phenotypes and relevance for clinical pathologies. Copyright © 2016 John Wiley & Sons, Ltd.
FMUC-Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal. rui.soares@uc.pt.|CNC-Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal. rui.soares@uc.pt.|IPO-Instituto Português de Oncologia Francisco Gentil, Coimbra, Portugal. rui.soares@uc.pt.
Rui
0000-0002-5513-6664
R
Soares
FMUC-Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.|Departamento de Doenças Infeciosas Hospital Pediátrico de Coimbra, CHUC-Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
Graça
G
Rocha
FMUC-Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.|Departamento de Doenças Infeciosas, CHUC - Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal.
António
A
Meliço-Silvestre
FMUC-Faculdade de Medicina, Universidade de Coimbra, Coimbra, Portugal.|CNC-Centro de Neurociências e Biologia Celular, Universidade de Coimbra, Coimbra, Portugal.
Teresa
T
Gonçalves
D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D015497:HIV-1 / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D016662:Virus Integration; D014779:Virus Replication; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics* / Q000378:metabolism*
D050505:Mutant Proteins; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1