Sheep-Associated Malignant Catarrhal Fever: Role of Latent Virus and Macrophages in Vasculitis

Abstract

Malignant catarrhal fever (MCF) is a sporadic, generally fatal disease caused by gammaherpesviruses in susceptible dead-end hosts. A key pathological process is systemic vasculitis in which productively infected cytotoxic T cells play a major role. Nonetheless, the pathogenesis of MCF vasculitis is not yet clear. We hypothesized that it develops due to an interaction between virus-infected cells and immune cells, and we undertook a retrospective in situ study on the rete mirabile arteries of confirmed ovine gammaherpesvirus-2 (OvHV-2)-associated MCF cases in cattle, buffalo, and bison. Our results suggest that the arteritis develops from an adventitial infiltration of inflammatory cells from the vasa vasorum, and recruitment of leukocytes from the arterial lumen that leads to a superimposed infiltration of the intima and media that can result in chronic changes including neointimal proliferation. We found macrophages and T cells to be the dominant infiltrating cells, and both could proliferate locally. Using RNA in situ hybridization and immunohistology, we showed that the process is accompanied by widespread viral infection, not only in infiltrating leukocytes but also in vascular endothelial cells, medial smooth muscle cells, and adventitial fibroblasts. Our results suggest that OvHV-2-infected T cells, monocytes, and locally proliferating macrophages contribute to the vasculitis in MCF. The initial trigger or insult that leads to leukocyte recruitment and activation is not yet known, but there is evidence that latently infected, activated endothelial cells play a role in this. Activated macrophages might then release the necessary pro-inflammatory mediators and, eventually, induce the characteristic vascular changes.

Neuroinvasion and Neurotropism by SARS-CoV-2 Variants in the K18-hACE2 Mouse

“…In selected cases, RNA ISH was performed using the RNAscope ® ISH method (Advanced Cell Diagnostics (ACD Advanced Cell Diagnostics, Newark, CA, USA)) and the RNAscope ® 2.5 Detection Reagent Kit (Brown) according to the manufacturer’s protocol and as previously described [ 51 , 52 ]. All cases were first tested for the suitability of the tissue (RNA preservation and quality) with an oligoprobe for Mus musculus peptidylprolyl isomerase B (PPIB) mRNA (ACD).…”

First Report of TTSuV1 in Domestic Swiss Pigs

“…After being tested by TTSuV1 real-time PCR and ISH, morphological lesions in 8 animals with mild non-suppurative inflammation in brain sections were further characterized using immunohistochemical/histochemical staining according to standard procedures [ 30 ]. The following antibodies were used ( Table 1 ): glial fibrillary acidic protein (GFAP) for astrocytes, ionized calcium-binding adaptor protein-1 (Iba-1) for macrophages/microglial cells, beta-amyloid precursor protein (beta-APP) for axonal damage, cluster of differentiation 3 (CD3) for T cells, cluster of differentiation 79a (CD79a) for B cells and forkhead box P3 (FOXP3) for regulatory T cells.…”

Neuroinvasion and neurotropism by SARS-CoV-2 variants in the K18-hACE2 mouse

“…RNA ISH was performed using the RNAscope® ISH method (Advanced Cell Diagnostics (ACD Advanced Cell Diagnostics, Newark, California) and the RNAscope® 2.5 Detection Reagent Kit (Brown) according to the manufacturer's protocol and as previously described (Salguero et al, 2021;Saura-Martinez et al, 2021). All cases were first tested for the suitability of the tissue (RNA preservation and quality) with an oligoprobe for Mus musculus peptidylprolyl isomerase B (PPIB) mRNA (ACD).…”