Ultra-Deep Sequencing of Feline Leukemia Virus Envelope Gene Variable Regions A/B

The determination of how retroviral mutant spectra change under selective pressure is essential in the development of antiretroviral strategies. Suitable models of selective pressure exerted on a retrovirus may include the immune response of resistant and susceptible hosts. In felids, infection with the oncogenic gammaretrovirus Feline leukemia virus (FeLV) is bound to several different outcomes, but the factors that determine the outcome of the infection have not yet been unraveled. FeLV is therefore an ideal candidate to study virus mutant spectrum dynamics during the course of infection. With this project, we proposed to investigate, using next-generation sequencing, the mutant spectrum of the two envelope glycoprotein hypervariable regions in susceptible and resistant FeLV-infected Iberian lynxes and experimentally infected domestic cats with different infection outcomes. The goal of the projects was the detection of conservation or elimination of specific variants of the retrovirus that may be crucial in determining the fitness of the virus and thus contribute substantially to its pathogenicity. Data generated so far allowed the assessment of the so far unknown sequence variability of FeLV within 238 bases of the variable region A (VRA) at 0.2% resolution. VRA mutations indicated partial apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) cytidine deaminase restriction of FeLV replication, but variants characteristic of aggressive FeLV strains like FeLV-C or FeLV-A/61C were not detectable. Results obtained so far contributed to set the basis for further experiments aimed at the analysis of FeLV mutant spectrum dynamics during the course of infection and its role in determining the infection outcome.