Out of the Reservoir: Phenotypic and Genotypic Characterization of a Novel …

Posted by Big Rat on Campus on Oct 3, 2015 in Rat News | Subscribe


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.

IMPORTANCE We 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.

Article source: http://jvi.asm.org/content/89/21/10959.abstract

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