Systemic vasculitis in sheep associated with ovine herpesvirus-2

Andrew Brooks, Amanda Mansz, Jan Shapiro

Animal Health Laboratory, University of Guelph, Guelph and Kemptville, ON

AHL Newsletter 2021;25(3):6.

Pathologists at the AHL have observed rare cases of systemic vasculitis in sheep which have lesions similar to malignant catarrhal fever (MCF) in cattle.  Between 2007 and 2009, the AHL laboratory in Kemptville observed multiple cases in eastern Ontario (1), and since then, there have been sporadic cases from other regions of the province.  Cases of MCF-like disease in sheep have also been reported in Alberta, Europe, and the United States (2-4). 

The clinical signs of this syndrome may include anorexia, oculonasal discharge, drooling, depression, recumbency and death.  Excessive salivation -“slobbering sheep” - was a characteristic clinical sign noted by the pathologists at Kemptville.  Affected sheep may be purebred or crossbred, lambs or adults.  Flocks may have single or multiple affected animals.  At postmortem, there may be prominent ulceration of the gastrointestinal mucosa including the oral cavity, tongue, esophagus and forestomachs (Fig. 1).

Histologically, vasculitis affecting multiple organs is a common feature of this syndrome (Fig. 2).  Ovine herpesvirus-2 (OvHV-2) is one of the ruminant gammaherpesviruses that causes MCF in cattle and other ungulates.  Since sheep are the adapted host for OvHV-2, infection is widespread and mostly asymptomatic in this species.  However, OvHV-2 can also cause disease in sheep.  There are reports of natural disease resembling MCF in domestic and wild sheep (2, 3), and lambs experimentally infected with OvHV-2 developed lesions similar to MCF (5).

Investigating OvHV-2 as a cause of disease in ovine laboratory submissions is challenging because infection would likely be detectable in most sheep by routine methods such as qualitative PCR or serology, regardless of disease status.  However, a novel in situ hybridization (ISH) method has revealed an association between the distribution of OvHV-2 nucleic acid and the vascular lesions in sheep with MCF-like disease, suggesting a causal role for OvHV-2 in this syndrome (4).

Three cases of systemic vasculitis in sheep were selected from the AHL archives for OvHV-2 ISH testing (Table 1). A subset of formalin-fixed paraffin-embedded tissues containing vascular lesions were tested for each case.  ISH was performed and interpreted by Dr. Patricia Pesavento (Department of Pathology, Microbiology & Immunology, University of California).  With respect to other potential causes of vasculitis, these cases did not have complete diagnostic testing but PCR tests for bluetongue virus (case 1 and 2) and border disease virus/BVDV (case 1) were negative.  The cases did not have lesions consistent with ovine lentivirus.

Cases 1 and 2 tested positive for OvHV-2 by ISH, and case 3 tested negative.  In the positive tissues, probe hybridization was detected in the nuclei of a subset of lymphocytes surrounding some, but not all, vessels with vasculitis in the kidney or heart (Fig. 3).  The ISH signal in the two positive cases was weak compared to the controls which may be due to prolonged tissue fixation in formalin. These results suggest that OvHV-2 is likely responsible for some cases of systemic vasculitis observed in sheep at the AHL.  OvHV-2 should be considered a potential etiology for sheep that exhibit clinical signs and lesions similar to MCF such as excessive salivation, gastrointestinal ulceration and systemic vasculitis.

The authors would like to thank Dr. Pesavento (University of California) for performing and interpreting the ISH, and the OAHN Small Ruminant Expert Network for financial support.   AHL

Table 1. Summary of ovine cases of systemic vasculitis tested for OvHV-2 by in situ hybridization.

Figure 1.  Multifocal ulceration (arrows) of the mucosa of the hard palate, case 1. 

Figure 2.  Lymphocytic vasculitis of a renal arteriole, case 2. H&E stain

Figure 3.  Positive OvHV-2 in situ hybridization (red chromogen, arrowheads) in lymphocytes surrounding an arteriole adjacent to a renal glomerulus, case 2

References

1. Shapiro J, Binnington B. Be on the look-out for an unusual mucosal disease in slobbering sheep. Ceptor 2009;17:4.

2. Slater OM, et al. Sheep-associated malignant catarrhal fever-like skin disease in a free-ranging bighorn sheep (Ovis canadensis), Alberta, Canada. J Wildl Dis 2017;53:153-158.

3. Gaudy J, et al. Possible natural MCF-like disease in a domestic lamb in Scotland. Vet Rec 2012;171:563.

4. Pesavento PA, et al. Systemic necrotizing vasculitis in sheep is associated with ovine herpesvirus 2. Vet Pathol 2019;56:87-92.

5. Li H, et al. Malignant catarrhal fever-like disease in sheep after intranasal inoculation with ovine herpesvirus-2. J Vet Diagn Invest 2005;17:171-175.