Clearance of Maedi-visna infection in a longitudinal study of naturally infected rams is associated with homozygosity for the TMEM154 resistance allele

Abstract

Maedi-visna (MV) is a lentiviral disease of sheep responsible for severe production losses in affected flocks. There are no vaccination or treatment options with control reliant on test and cull strategies. The most common diagnostic methods used at present are combination ELISAs for Gag and Env proteins with virus variability making PCR diagnostics still largely an experimental tool. To assess variability in viral loads and diagnostic tests results, serology, DNA and RNA viral loads were measured in the blood of 12 naturally infected rams repeatedly blood sampled over 16 months. Six animals tested negative in one or more tests at one or more time points and would have been missed on screening programmes reliant on one test method or a single time point. In addition the one animal homozygous for the ‘K’ allele of the TMEM154 E35K SNP maintained very low viral loads in all assays and apparently cleared infection to below detectable limits at the final time point it was sampled. This adds crucial data to the strong epidemiological evidence that this locus represents a genuine resistance marker for MV infection and is a strong candidate for selective breeding of sheep for resistance to disease.

Impact of Four Ovine TMEM154 Haplotypes on Ewes during Multiyear Lentivirus Exposure

“…The lack of disease progression among seropositive “4,4” diplotype ewes suggest that animals with the least susceptible diplotype combinations may have limited viral replication. This is consistent with a recent report of a “1,1” diplotype ram that maintained very low viral loads and ultimately apparently cleared infection to below detectable limits [ 22 ]. This phenomenon may be a possible explanation for inconsistent report of performance levels of serologically positive sheep compared to serologically negative sheep when using point in time surveys [ 1 , 2 , 23 , 24 ].…”

“…A second weakness of the study was using serostatus as a proxy for infection. Recent reports of cleared VMV infections [ 22 ], and the lack of disease progression in ewes with “4,4” diplotypes now raise the possibility that ewes with “1,1”, “1,4” and “4,4” diplotypes can clear infections. A third weakness was necropsy of only “4,4” diplotype sheep to test disease progression.…”

>b<Estudo dos diferentes genótipos de lentivírus de pequenos ruminantes no Brasil e sua relação com manifestações clínicas>/b<

“…Embora os resultados preliminares sejam promissores, ainda é necessária a realização de estudos complementares, como por exemplo, averiguar se as associações encontradas entre a resistência genética de algumas raças também ocorre com a exposição a diferentes cepas virulentas (YAMAN et al, 2019). É necessário avaliar se o melhoramento genético a resistência a infecção por LVPR poderia acarretar possíveis impactos negativos sobre as características produtivas para esse tipo de seleção (JONES et al, 2022).…”