CD8+ T cell antiviral activity: mechanism of induction and the suppression of emerging feline immunodeficiency virus strains
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In the present studies, the essential role of inducer cells for the induction of soluble anti-viral activity against feline immunodeficiency virus (FIV) was investigated. Induction of suppression of FIV replication was found to not strictly require autologous cells and was probably not FIV specific. Suppression was maximum when the inducer cells and the effector CD8+ T cells were in contact with each other, suggesting a potential role for membrane antigen interactions and/or cytokines in the induction process. Additionally, flow cytometry analysis demonstrated a significant increase in the percentage of CD8+ B7-1+ T cells in the peripheral blood of chronically FIV infected cats as compared with uninfected cats. Examination of the FIV V3-V4 envelope sequences from PBMC, lymph nodes and spleen from six cats chronically infected from three to six years with the molecular clone of FIV-PPR did not demonstrate viral variants specific for the tissues examined, emphasizing the critical role of the initial diversity and virulence of the infecting virus inoculum. Additionally, in vitro CD8+ T cell antiviral activity demonstrated by four of the six cats could have led to the control of virus replication in vivo, resulting in the uniform viral variants observed. Infection of specific pathogen free cats with FIV-TX53, an FIV isolate that belongs to an emerging subtype more closely related to FIV clade B, demonstrated an acute stage infection characterized by lymphoadenopathy and a viral dose dependent decline of CD4+/CD8+ T cell ratios below 1 by 11 weeks post infection. Interestingly, an expansion of CD8 low population of CD8+ T cells was observed in the infected cats. The soluble antiviral activity generated from inducer T cell stimulated CD8+ T cells from FIV-A-PPR infected cats also suppressed in vitro replication of the emerging FIV-TX53 and FIV-TX078 isolates. This is the first report demonstrating that the CD8+ T cell antiviral activity is inter-clade effective among FIV strains. As the success of a FIV vaccine could be hampered by occurrence of highly divergent viral variants in the fields, the exploitation of this innate, soluble anti-FIV activity could contribute to the design of novel, safe and complementary anti-FIV therapeutic strategies.