Feline immunodeficiency virus envelope glycoprotein mediates apoptosis in activated PBMC by a mechanism dependent on gp41 function.
Feline Immunodeficiency Virus (FIV) is a lentivirus that causes immunodeficiency in cats, which parallels HIV-1-induced immunodeficiency in humans. It has been established that HIV envelope (Env) glycoprotein mediates T cell loss via a mechanism that requires CXCR4 binding. The Env glycoprotein of FIV, similar to HIV, requires CXCR4 binding for viral entry, as well as inducing membrane fusion leading to syncytia formation. However, the role of FIV Env in T cell loss and the molecular mechanisms governing this process have not been elucidated. We studied the role of Env glycoprotein in FIV-mediated T cell apoptosis in an in vitro model. Our studies demonstrate that membrane-expressed FIV Env induces apoptosis in activated feline peripheral blood mononuclear cells (PBMC) by a mechanism that requires CXCR4 binding, as the process was inhibited by CXCR4 antagonist AMD3100 in a dose-dependent manner. Interestingly, studies regarding the role of CD134, the recently identified primary receptor of FIV, suggest that binding to CD134 may not be important for induction of apoptosis in PBMC. However, inhibiting Env-mediated fusion post CXCR4 binding by FIV gp41-specific fusion inhibitor also inhibited apoptosis. Under similar conditions, a fusion-defective gp41 mutant was unable to induce apoptosis in activated PBMC. Our findings are the first report suggesting the potential of FIV Env to mediate apoptosis in bystander cells by a process that is dependent on gp41 function.
Garg
Himanshu
H
Immunology Program, College of Veterinary Medicine, North Carolina State University, Raleigh, NC 27606, USA.
Joshi
Anjali
A
Tompkins
Wayne A
WA
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology; D017209:Apoptosis; D001596:Benzylamines; D002415:Cats; D002459:Cell Fusion; D002470:Cell Survival; D002478:Cells, Cultured; D000080027:Cyclams; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D006571:Heterocyclic Compounds / Q000494:pharmacology; D016089:Immunodeficiency Virus, Feline / Q000472:pathogenicity*; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000821:virology*; D008561:Membrane Fusion; D009154:Mutation / Q000235:genetics / Q000502:physiology; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D014759:Viral Envelope Proteins / Q000235:genetics / Q000502:physiology*; D014760:Viral Fusion Proteins / Q000235:genetics / Q000502:physiology*
D019380:Anti-HIV Agents; D001596:Benzylamines; D000080027:Cyclams; D006023:Glycoproteins; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D014759:Viral Envelope Proteins; D014760:Viral Fusion Proteins; C445079:envelope protein, Feline immunodeficiency virus; C088327:plerixafor