HIV-1 Vpr and anti-inflammatory activity.
New and effective approaches for inflammatory diseases based on novel mechanisms of action are needed. One potential source of anti-inflammatory drugs exists among viruses. Viruses have evolved to infect, replicate within, and kill human cells through diverse mechanisms. They accomplish this fact by finding ways to out with the host's complex immune machinery. It is possible that the viral proteins and pathways involved in the downregulation of host immune function during infection can be exploited as a therapeutic in diseases that result in the overactivity of the immune system. Indeed, the human immunodeficiency virus type 1 (HIV-1) protein, Vpr, affects cells in a number of ways that may prove useful for exploitation for the treatment of inflammatory diseases. Vpr has effects on T-cell proliferation, cytokine production, chemokine production, and Nuclear Factor kappa B (NF-kappaB)-mediated transcription. Importantly, it has been observed that Vpr downregulates NF-kappaB and the production of pro-inflammatory cytokines such as TNF-alpha, and IL-12. These activities are worthy of further examination for control of hyperinflammatory and hyperproliferative conditions.
Muthumani
Karuppiah
K
Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
Desai
Brijal M
BM
Hwang
Daniel S
DS
Choo
Andrew Y
AY
Laddy
Dominick J
DJ
Thieu
Khanh P
KP
Rao
Rushil G
RG
Weiner
David B
DB
D018925:Chemokines / Q000378:metabolism; D015536:Down-Regulation; D016336:Gene Products, vpr / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000628:therapy*; D018664:Interleukin-12 / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus
D018925:Chemokines; D016336:Gene Products, vpr; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D054325:vpr Gene Products, Human Immunodeficiency Virus; D018664:Interleukin-12