Host-virus interactions and molecular epidemiology of the feline immunodeficiency virus

Mammalian lentiviruses infect monocyte-derived cells causing organ-specific lesions, but the primate lentiviruses and the feline immunodeficiency virus (FIV) also infect CD4+ lymphocytes and may lead to immunosuppression. Although FIV has a broader range of lymphocyte targets, only CD4+ cells are depleted, offering opportunities to investigate the causes of their selective loss. Different FIV strains vary in pathogenicity, but whether specific subtypes are more pathogenic than others is unknown. Nonetheless, the high genetic variability of FIV strains poses a challenge for diagnostics and vaccine development. The first part of this study investigated differential susceptibility of primary feline hematopoietic cells to infection with FIV by assessing expression of FIV receptors, and the ability of a cloned and a primary isolate of FIV to replicate in vitro. Also, the prevailing FIV subtypes circulating in Canada were characterized and a virus-independent approach of vaccination was tested. All cell types expressed the FIV receptors CD134 and CXCR4, and supported productive infection with the virus, but CD4 + lymphocytes showed the highest level of expression of entry receptors, and were the most permissive cells for viral replication. Although differential pathogenicity was not attributable to any particular subtype, subtype A was the most prevalent in Canada, and an A/B intersubtype recombinant isolate naturally circulating among cats in Ontario was identified. Findings from this study suggested that the selective depletion of CD4+ lymphocytes might be in part attributable to their density of FIV-specific receptors. Also, new FIV subtypes prevailing in Canada were identified, which might be relevant for vaccine design. Vaccination approaches against FIV involving whole viruses or viral antigens have had limited success to date, and in this study, a novel strategy based on induction of allogeneic immunity was also of limited efficacy. FIV, like other immunodeficiency-inducing lentiviruses, has complex cell entry and replication strategies, which, if combined with rapid and extensive antigenic variability, pose formidable challenges for the development of therapeutic and prophylactic intervention.