Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus (FIV)

Analysing the evolution of FIV on the intra-host level is important, in order to address whether the diversity and composition of viral quasispecies affects disease progression.<p></p> We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at the rate of 1.16 x 10-3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3-V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3-V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation.<p></p> Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximal evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared to HIV might explain why many naturally infected cats do not progress to AIDS rapidly.<p></p&gt

Emergence of CD134 cysteine-rich domain 2 (CRD2)-independent strains of feline immunodeficiency virus (FIV) is associated with disease progression in naturally infected cats

<b>Background</b> Feline immunodeficiency virus (FIV) infection is mediated by sequential interactions with CD134 and CXCR4. Field strains of virus vary in their dependence on cysteine-rich domain 2 (CRD2) of CD134 for infection.<p></p> <b>Findings</b> Here, we analyse the receptor usage of viral variants in the blood of 39 naturally infected cats, revealing that CRD2-dependent viral variants dominate in early infection, evolving towards CRD2-independence with disease progression.<p></p> <b>Conclusions</b> These findings are consistent with a shift in CRD2 of CD134 usage with disease progression.<p></p&gt