An Increasing Danger of Zoonotic Orthopoxvirus Infections

Щелкунов, С. Н.

doi:10.1371/journal.ppat.1003756

Cited by 199 publications

(201 citation statements)

References 54 publications

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“…The number of human CPXV infections is growing, possibly due to the cessation of smallpox vaccination since its official eradication was made public in 1978 (37). Above all, animal caretakers and veterinarians having contact with infected accidental hosts are at risk of infection with CPXV.…”

Section: Discussionmentioning

confidence: 99%

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

Hoffmann

Franke

Jenckel

et al. 2015

J Virol

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The incidence of human cowpox virus (CPXV) infections has increased significantly in recent years. Serological surveys have suggested wild rodents as the main CPXV reservoir. We characterized a CPXV isolated during a large-scale screening from a feral common vole. A comparison of the full-length DNA sequence of this CPXV strain with a highly virulent pet rat CPXV isolate showed a sequence identity of 96%, including a large additional open reading frame (ORF) of about 6,000 nucleotides which is absent in the reference CPXV strain Brighton Red. Electron microscopy analysis demonstrated that the vole isolate, in contrast to the rat strain, forms A-type inclusion (ATI) bodies with incorporated virions, consistent with the presence of complete ati and p4c genes. Experimental infections showed that the vole CPXV strain caused only mild clinical symptoms in its natural host, while all rats developed severe respiratory symptoms followed by a systemic rash. In contrast, common voles infected with a high dose of the rat CPXV showed severe signs of respiratory disease but no skin lesions, whereas infection with a low dose led to virus excretion with only mild clinical signs. We concluded that the common vole is susceptible to infection with different CPXV strains. The spectrum ranges from well-adapted viruses causing limited clinical symptoms to highly virulent strains causing severe respiratory symptoms. In addition, the low pathogenicity of the vole isolate in its eponymous host suggests a role of common voles as a major CPXV reservoir, and future research will focus on the correlation between viral genotype and phenotype/ pathotype in accidental and reservoir species. IMPORTANCEWe report on the first detection and isolation of CPXV from a putative reservoir host, which enables comparative analyses to understand the infection cycle of these zoonotic orthopox viruses and the relevant genes involved. In vitro studies, including whole-genome sequencing as well as in vivo experiments using the Wistar rat model and the vole reservoir host allowed us to establish links between genomic sequences and the in vivo properties (virulence) of the novel vole isolate in comparison to those of a recent zoonotic CPXV isolated from pet rats in 2009. Furthermore, the role of genes present only in a reservoir isolate can now be further analyzed. These studies therefore allow unique insights and conclusions about the role of the rodent reservoir in CPXV epidemiology and transmission and about the zoonotic threat that these viruses represent. C owpox virus (CPXV), a member of the genus Orthopoxvirus (OPV) in the Poxviridae family, is suspected to be widespread in Western Eurasian rodents, particularly vole species (1, 2). From the presumed reservoir hosts, spill-over infections to accidental hosts are regularly observed (3). The accidental hosts include domestic cats and also exotic animals in zoos, such as large felids and elephants, which regularly develop severe disease (3). As CPXV is a zoonotic virus, humans in direct contact wit...

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Section: Discussionmentioning

confidence: 99%

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

Hoffmann

Franke

Jenckel

et al. 2015

J Virol

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“…Human cowpox is a rare sporadic disease, which develops when the virus is transmitted from an infected animal to humans. This disease is mainly recorded in Europe [1].…”

Section: Discussionmentioning

confidence: 99%

“…Small rodents, such as voles and mice, are considered a natural reservoir. No transmission between humans has been reported so far [1][2][3].…”

Section: Introductionmentioning

confidence: 96%

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Cowpox virus infection from pet rat

Wollina¹,

Hansel²,

Schönlebe³

2018

Our Dermatol Online

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“…On the recommendation of the WHO, the vaccination program was stopped in the 1980s because of severe side effects of the vaccine. The number of people lacking immunity against smallpox and other zoonotic OPXV infections is therefore increasing (Shchelkunov, 2013). Consequently, a potential biowarfare attack with smallpox would hit a nearly unprotected population.…”

Section: Introductionmentioning

confidence: 99%

Limited susceptibility of rhesus macaques to a cowpox virus isolated from a lethal outbreak among New World monkeys

et al. 2017

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Abstract. This study was undertaken to investigate the susceptibility of rhesus monkeys to the calpox virus, an orthopoxvirus (OPXV) of the Cowpox virus species (CPXV), which is uniformly lethal in common marmosets. Six rhesus monkeys were either intravenously (i.v.) or intranasally (i.n.) exposed to the virus. Monitoring of the macaques after viral exposure included physical examinations, the determination of viral load by real-time PCR and plaque assay, and the analysis of humoral responses. Two i.v. inoculated animals developed numerous classical pox lesions that started after inoculation at days 7 and 10. Both animals became viremic and seroconverted. They exhibited maximal numbers of lesions of approximately 50 and 140 by day 21. One animal completely recovered, while the other one suffered from a phlegmonous inflammation of a leg initially induced by a secondarily infected pox lesion and was euthanized for animal welfare reasons. In contrast to previous pathogenicity studies with the calpox virus in marmosets, none of the four animals inoculated intranasally with doses of the calpox virus exceeding those used in marmosets by orders of magnitude showed typical clinical symptoms. No viral DNA was detectable in the blood of those animals, but three animals seroconverted. In two of these three animals, infectious virus was sporadically isolated from saliva. This indicates that rhesus monkeys are less susceptible to calpox virus infection, which limits their use in further intervention studies with OPXV.

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An Increasing Danger of Zoonotic Orthopoxvirus Infections

Cited by 199 publications

References 54 publications

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel Cowpox Virus Isolated from a Common Vole

Cowpox virus infection from pet rat

Limited susceptibility of rhesus macaques to a cowpox virus isolated from a lethal outbreak among New World monkeys

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