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

Scott Jones,Rachael Tarlinton,Nicola Bollard,Stephen Dunham,Heather Mckay,Peers Davies,Laura Eden

doi:10.1099/jmm.0.001506

Scott Jones, Rachael Tarlinton + Show 5 more

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https://doi.org/10.1099/jmm.0.001506

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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.

Highlights

Small ruminant lentiviruses (SRLVs) including Maedi-v isna (MV) and Caprine Arthritis-E ncephalitis (CAE) are lentiviral diseases of sheep and goats respectively that have a severe economic impact on infected flocks
The results of this study demonstrate some of the confounding factors with current MV diagnostics
Screening and control strategies for MV rely on multiple serology screens of flocks at least 6 months apart as in the UK's premium sheep health and goat schemes [29]

Summary

Introduction

Small ruminant lentiviruses (SRLVs) including Maedi-v isna (MV) and Caprine Arthritis-E ncephalitis (CAE) are lentiviral diseases of sheep and goats respectively that have a severe economic impact on infected flocks. SRLVs infect monocytes and remain dormant until these mature into macrophages, it has a very long latent period with clinical signs often not developing for several years. In sheep MV is primarily a respiratory disease with affected lungs greatly enlarged and displaying typical macrophage infiltrations, though encephalitis and mastitis are clinical syndromes associated with virus infection [1]. SRLVs in common with other lentiviruses display extreme genetic hypervariability [2] which has meant that to date the development of effective vaccines has been unsuccessful; in some cases experimental vaccines have even enhanced infection [3]. Mutations in TMEM154 (function unknown) were first identified as potential MV resistance allelles in a genome wide association study of naturally infected ewes [11, 12].

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