Abstract Background In the acute phase of infection with feline immunodeficiency virus (FIV), the virus targets activated CD4+ T cells by utilising CD134 (OX40) as a primary attachment receptor and CXCR4 as a co-receptor.The nature of the virus-receptor interaction varies between isolates; strains such as GL8 and CPGammer recognise a "complex" Ironing Board Cover determinant on CD134 formed by cysteine-rich domains (CRDs) 1 and 2 of the molecule while strains such as PPR and B2542 require a more "simple" determinant comprising CRD1 only for infection.These differences in receptor recognition manifest as variations in sensitivity to receptor antagonists.In this study, we ask whether the nature of the virus-receptor interaction evolves in vivo.Results Following infection with a homogeneous viral population derived from a pathogenic molecular clone, a quasispecies emerged comprising variants with distinct sensitivities to neutralising antibody and displaying evidence of conversion from a "complex" to a "simple" interaction with CD134.
Escape from neutralising antibody was mediated primarily by length and sequence polymorphisms in the V5 region of Env, and these alterations in V5 modulated the virus-receptor interaction as indicated by altered sensitivities to antagonism by both anti-CD134 antibody and soluble CD134.Conclusions The FIV-receptor interaction evolves under the selective pressure of the host humoral immune response, and the V5 loop contributes Idler Pulley to the virus-receptor interaction.Our data are consistent with a model whereby viruses with distinct biological properties are present in early versus late infection and with a shift from a "complex" to a "simple" interaction with CD134 with time post-infection.