Restriction of feline retroviruses: lessons from cat APOBEC3 cytidine deaminases and TRIM5alpha proteins.

The interplay between viral and cellular factors determines the outcome of an initial contact between a given virus and its natural host or upon encounter of a novel host. Thus, the potential of inducing disease as well as crossing host species barriers are the consequences of the molecular interactions between the parasite and its susceptible, tolerant or resistant host. Cellular restriction factors, for instance APOBEC3 and TRIM5 proteins, targeting defined pathogens or groups of pathogens as well as viral genes counter-acting these cellular defense systems are of prime importance in this respect and may even represent novel targets for prevention and therapy of virus infections. Due to the importance of host-encoded antiviral restriction and viral counter-defense for pathogenicity and host tropism, the responsible molecular factors and mechanisms are currently under intense investigation. In this review we will introduce host restriction and retroviral counter-defense systems with a special emphasis on the cat and its naturally occurring exogenous retroviruses which is a valid model for human disease, a model that will contribute to increase our basic understanding and potential applications of these important aspects of host-virus interaction.

Feline lentiviruses demonstrate differences in receptor repertoire and envelope structural elements.

Feline immunodeficiency virus (FIV) causes fatal disease in domestic cats via T cell depletion-mediated immunodeficiency. Pumas and lions are hosts for apparently apathogenic lentiviruses (PLV, LLV) distinct from FIV. We compared receptor use among these viruses by: (1) evaluating target cell susceptibility; (2) measuring viral replication following exposure to specific and non-specific receptor antagonists; and (3) comparing Env sequence and structural motifs. Most isolates of LLV and PLV productively infected domestic feline T cells, but differed from domestic cat FIV by infecting cells independent of CXCR4, demonstrating equivalent or enhanced replication following heparin exposure, and demonstrating substantial divergence in amino acid sequence and secondary structure in Env receptor binding domains. PLV infection was, however, inhibited by CD134/OX40 antibody. Thus, although PLV and LLV infection interfere with FIV superinfection, we conclude that LLV and PLV utilize novel, more promiscuous mechanisms for cell entry than FIV, underlying divergent tropism and biological properties of these viruses.