TNF and TNF receptor superfamily members in HIV infection: new cellular targets for therapy?
Tumor necrosis factor (TNF) and TNF receptors (TNFR) superfamily members are engaged in diverse cellular phenomena such as cellular proliferation, morphogenesis, apoptosis, inflammation, and immune regulation. Their role in regulating viral infections has been well documented. Viruses have evolved with numerous strategies to interfere with TNF-mediated signaling indicating the importance of TNF and TNFR superfamily in viral pathogenesis. Recent research reports suggest that TNF and TNFRs play an important role in the pathogenesis of HIV. TNFR signaling modulates HIV replication and HIV proteins interfere with TNF/TNFR pathways. Since immune activation and inflammation are the hallmark of HIV infection, the use of TNF inhibitors can have significant impact on HIV disease progression. In this review, we will describe how HIV infection is modulated by signaling mediated through members of TNF and TNFR superfamily and in turn how these latter could be targeted by HIV proteins. Finally, we will discuss the emerging therapeutics options based on modulation of TNF activity that could ultimately lead to the cure of HIV-infected patients.
Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France.
Amit
A
Kumar
Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France.
Wasim
W
Abbas
Department of Virology, University of Franche-Comte, CHRU Besançon, UPRES EA4266 Pathogens & Inflammation, SFR FED 4234, 25030 Besançon, France ; Department of Virology, University of Franche-Comte, Hôpital Saint-Jacques, 2 Place Saint-Jacques, 25030 Besançon Cedex, France.
Georges
G
Herbein
D017209:Apoptosis; D019013:CD40 Antigens / Q000502:physiology; D023201:CD40 Ligand / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000209:etiology / Q000276:immunology*; D006801:Humans; D053259:Lymphotoxin beta Receptor / Q000502:physiology; D053262:Receptors, OX40 / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors / Q000502:physiology*; D015398:Signal Transduction; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*
D019013:CD40 Antigens; D053259:Lymphotoxin beta Receptor; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D023201:CD40 Ligand