A Point Mutation in a Herpesvirus Co-Determines Neuropathogenicity and Viral Shedding.

Mathias Franz,Gerlinde Van De Walle,Alex Greenwood,Nikolaus Osterrieder,Laura Goodman

doi:10.3390/v9010006

Abstract

A point mutation in the DNA polymerase gene in equine herpesvirus type 1 (EHV-1) is one determinant for the development of neurological disease in horses. Three recently conducted infection experiments using domestic horses and ponies failed to detect statistically significant differences in viral shedding between the neuropathogenic and non-neuropathogenic variants. These results were interpreted as suggesting the absence of a consistent selective advantage of the neuropathogenic variant and therefore appeared to be inconsistent with a systematic increase in the prevalence of neuropathogenic strains. To overcome potential problems of low statistical power related to small group sizes in these infection experiments, we integrated raw data from all three experiments into a single statistical analysis. The results of this combined analysis showed that infection with the neuropathogenic EHV-1 variant led to a statistically significant increase in viral shedding. This finding is consistent with the idea that neuropathogenic strains could have a selective advantage and are therefore systematically increasing in prevalence in domestic horse populations. However, further studies are required to determine whether a selective advantage indeed exists for neuropathogenic strains.

Highlights

Equine herpesvirus type 1 (EHV-1) is a ubiquitous alphaherpesvirus that can cause respiratory disease, abortion, neonatal foal death and equine herpes myeloencephalopathy (EHM), a neurological disease that can be lethal [1,2]
Results of our combined analysis showed that the amount of EHV-1 nasal shedding was significantly increased in animals infected with the D752 variant compared with infection with the
The model indicated that infections with the D752 variant led, on average, to a four-fold higher amount of nasal EHV-1 shedding compared to infections with the N752 variant (Figure 1)

Summary

Introduction

Equine herpesvirus type 1 (EHV-1) is a ubiquitous alphaherpesvirus that can cause respiratory disease, abortion, neonatal foal death and equine herpes myeloencephalopathy (EHM), a neurological disease that can be lethal [1,2]. It is not well understood how EHM develops following EHV-1 infection, it has been shown that neuropathogenicity is significantly associated with a single nucleotide polymorphism in the viral DNA polymerase, resulting in a specific amino acid change; asparagine to aspartic acid (N/D752 ) [1,2,3]. Involvement of a variety of host, viral, and environmental risk factors are known or suspected, infections with D752 strains strongly increase the risk of developing EHM [1].

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