Virus ontogeny:How zoonotic viruses interact with their reservoir hosts

Emerging infectious viral diseases in humans frequently arise from their changing contacts with animals. By studying these virus infections in their original animal host species, we can also gain insights into the pathogeneses of these virus infections in humans

The pathogenesis of zoonotic viral infections:Lessons learned by studying reservoir hosts

Zoonotic viral infections that cause severe disease or even death in some people may be asymptomatic or mild in reservoir hosts. Comparison of the pathogenesis of these two host categories may potentially explain the difference in disease. However, infections in reservoir hosts are often neglected. Therefore, we compared the pathogenesis of rabies virus, macacine alphaherpesvirus, West Nile virus, Puumala orthohantavirus, monkeypox virus, Lassa mammarenavirus, H5N1 highly pathogenic avian influenza, Marburg virus, Nipah virus, Middle East respiratory syndrome, and simian/human immunodeficiency viruses in both humans and reservoir hosts. We showed that most aspects of the pathogeneses were remarkably similar. The remaining differences lead to the identification of tipping points in the pathogeneses that are important for explaining the disease outcome in severe human cases. Further elucidating these tipping points by studying zoonotic viral infections in their reservoir hosts may teach us how to reduce the severity of zoonotic viral diseases in humans.</p

Inhibition of caspase-1 prolongs survival of mice infected with rabies virus

Rabies virus infects almost all mammals resulting in lethal disease. To date there is no treatment available for symptomatic rabies and there is an urgent need to develop treatment strategies that would prolong survival, thereby providing a window of opportunity for the host to mount a protective immune response. We hypothesized that both virus and excessive immune response contribute to disease and that interfering with both is necessary to prevent lethal disease. Here, we have inhibited the pro-inflammatory response associated with pyroptosis and showed that inhibition of CASP-1 had a beneficial effect on survival time. Our results confirm that some inflammatory responses may be involved in the pathogenesis of severe disease and the results suggest that effective intervention includes inhibition of virus and host response

The first report of <i>Listeria monocytogenes</i> detected in pinnipeds

The aim of this study was to describe the pathology in seals from which Listeria monocytogenes was isolated and investigate if the lesions’ nature and severity were related to the phylogeny of isolates. L. monocytogenes was isolated from 13 of 50 (26%) dead grey seal (Halichoerus grypus) pups, six (12%) in systemic distribution, on the Isle of May, Scotland. Similar fatal L. monocytogenes-associated infections were found in a grey seal pup from Carnoustie, Scotland, and a juvenile harbour seal (Phoca vitulina) in the Netherlands. Whole genome sequencing of 15 of the L. monocytogenes isolates identified 13 multilocus sequence types belonging to the L. monocytogenes lineages I and II, but with scant phenotypic and genotypic antimicrobial resistance and limited variation in virulence factors. The phylogenetic diversity present suggests there are multiple sources of L. monocytogenes, even for seal pups born in the same colony and breeding season. This is the first description of L. monocytogenes isolated from, and detected in lesions in, pinnipeds and indicates that infection can be systemic and fatal. Therefore, listeriosis may be an emerging or overlooked disease in seals with infection originating from contamination of the marine environment.</p

The first report of Listeria monocytogenes detected in pinnipeds

The aim of this study was to describe the pathology in seals from which Listeria monocytogenes was isolated and investigate if the lesions’ nature and severity were related to the phylogeny of isolates. L. monocytogenes was isolated from 13 of 50 (26%) dead grey seal (Halichoerus grypus) pups, six (12%) in systemic distribution, on the Isle of May, Scotland. Similar fatal L. monocytogenes-associated infections were found in a grey seal pup from Carnoustie, Scotland, and a juvenile harbour seal (Phoca vitulina) in the Netherlands. Whole genome sequencing of 15 of the L. monocytogenes isolates identified 13 multilocus sequence types belonging to the L. monocytogenes lineages I and II, but with scant phenotypic and genotypic antimicrobial resistance and limited variation in virulence factors. The phylogenetic diversity present suggests there are multiple sources of L. monocytogenes, even for seal pups born in the same colony and breeding season. This is the first description of L. monocytogenes isolated from, and detected in lesions in, pinnipeds and indicates that infection can be systemic and fatal. Therefore, listeriosis may be an emerging or overlooked disease in seals with infection originating from contamination of the marine environment.</p

Local amplification of highly pathogenic avian influenza H5N8 viruses in wild birds in the Netherlands, 2016 to 2017

Introduction: Highly pathogenic avian influenza (HPAI) viruses of subtype H5N8 were re-introduced into the Netherlands by late 2016, after detections in southeast Asia and Russia. This second H5N8 wave resul

A Dutch highly pathogenic H5N6 avian influenza virus showed remarkable tropism for extra-respiratory organs and caused severe disease but was not transmissible via air in the ferret model

Continued circulation of A/H5N1 influenzaviruses of the A/goose/Guangdong/1/96 lineage in poultry has resulted in the diversificationin multiple genetic and antigenic clades. Since 2009, clade 2.3.4.4 hemagglutinin (HA) containing viruses harboring the internal and neuraminidase (NA) genes of other avian influenzaA viruses have been detected. As a result, various HA-NA combinations, such as A/H5N1, A/H5N2, A/H5N3, A/H5N5, A/H5N6, and A/H5N8 have been identified.As of January 2023, 83 humans have been infected with A/H5N6 viruses, thereby posing an apparent risk for public health. Here, as part of a risk assessment, the in vitro and in vivo characterization of A/H5N6 A/black-headed gull/Netherlands/29/2017 is described. This A/H5N6 virus was not transmitted between ferrets via the air but was of unexpectedly high pathogenicity compared to other described A/H5N6 viruses. The virus replicated and caused severe lesions not only in respiratory tissues but also in multiple extra-respiratory tissues, including brain, liver, pancreas, spleen, lymph nodes, and adrenal gland. Sequence analyses demonstrated that the well-known mammalian adaptation substitution D701N was positively selected in almost all ferrets. In the in vitro experiments, no other known viral phenotypic properties associated with mammalian adaptation or increased pathogenicity were identified.The lack of transmission via the air and the absence of mammalian adaptation markers suggest that the public health risk of this virus is low. The high pathogenicity of this virus in ferrets could not be explained by the known mammalian pathogenicity factors and should be further studied.</p

The Bank Vole (Clethrionomys glareolus) - Small Animal Model for Hepacivirus Infection

Many people worldwide suffer from hepatitis C virus (HCV) infection, which is frequently persistent. The lack of efficient vaccines against HCV and the unavailability of or limited compliance with existing antiviral therapies is problematic for health care systems worldwide. Improved small animal models would support further hepacivirus research, including development of vaccines and novel antivirals. The recent discovery of several mammalian hepaciviruses may facilitate such research. In this study, we demonstrated that bank voles (Clethrionomys glareolus) were susceptible to bank vole-associated Hepacivirus F and Hepacivirus J strains, based on the detection of hepaciviral RNA in 52 of 55 experimentally inoculated voles. In contrast, interferon α/β receptor deficient C57/Bl6 mice were resistant to infection with both bank vole hepaciviruses (BvHVs). The highest viral genome loads in infected voles were detected in the liver, and viral RNA was visualized by in situ hybridization in hepatocytes, confirming a marked hepatotropism. Furthermore, liver lesions in infected voles resembled those of HCV infection in humans. In conclusion, infection with both BvHVs in their natural hosts shares striking similarities to HCV infection in humans and may represent promising small animal models for this important human disease