Genetic Susceptibility to Lentivirus Infection in Sheep

Ovine lentivirus affects the host immune system causing a persistent retroviral infection affecting millions of sheep around the world. In primates, lentivirus resistance is attributed to mutant virus coreceptors that are not expressed. In sheep, some animals are resistant to lentivirus infection despite repeated exposure; however, the mechanism of resistance is unknown. Recently, our genome-wide association study identified a transmembrane protein gene associated with lentivirus infection and containing a surprising number of missense and deletion mutations.  The pattern of mutation suggests that reduced function of this transmembrane protein interferes with the virus infection cycle, and that sheep without a functional copy of this gene have a selective advantage in populations with endemic infection.