Emergence of Cowpox: Study of the Virulence of Clinical Strains and Evaluation of Antivirals

Abstract

The last years, cowpox infections are being increasingly reported through Eurasia. Cowpox viruses (CPXVs) have been reported to have different genotypes and may be subdivided in at least five genetically distinct monophyletic clusters. However, little is known about their in vitro and in vivo features. In this report, five genetically diverse CPXVs, including one reference strain (CPXV strain Brighton) and four clinical isolates from human and animal cases, were compared with regard to growth in cells, pathogenicity in mice and inhibition by antivirals. While all CPXVs replicated similarly in vitro and showed comparable antiviral susceptibility, marked discrepancies were seen in vivo, including differences in virulence with recorded mortality rates of 0%, 20% and 100%. The four CPXV clinical isolates appeared less pathogenic than two reference strains, CPXV Brighton and vaccinia virus Western-Reserve. Disease severity seemed to correlate with high viral DNA loads in several organs, virus titers in lung tissues and levels of IL-6 cytokine in the sera. Our study highlighted that the species CPXV consists of viruses that not only differ considerably in their genotypes but also in their in vivo phenotypes, indicating that CPXVs should not be longer classified as a single species. Lung virus titers and IL-6 cytokine level in mice may be used as biomarkers for predicting disease severity. We further demonstrated the potential benefit of cidofovir, CMX001 and ST-246 use as antiviral therapy.

Elimination of A-type inclusion formation enhances cowpox virus replication in mice: Implications for orthopoxvirus evolution

“…CPXV 91/3 caused only a mild disease when administered i.n. to BALB/c mice as also recently found by others using a different mouse strain (Duraffour et al, 2013). However, mice inoculated i.n.…”

Serologic Survey of Orthopoxvirus Infection Among Rodents in Hungary

“…The clinical manifestations of CPXV are local skin scabs; systemic infections develop most typically in immunocompromised hosts. Descriptions of human infection have increased since the late 1980s, most likely because of the termination of the smallpox vaccinations (Vorou et al 2008, Duraffour et al 2013, Shchelkunov 2013.…”

Active vaccination with vaccinia virus A33 protects mice against lethal vaccinia and ectromelia viruses but not against cowpoxvirus; elucidation of the specific adaptive immune response

“…CPXV is a rodent orthopoxvirus found in nature in the northern parts of Europe and Asia and occasionally causes emerging zoonosis [2,31,32]. This virus causes a lethal disease in lab mice that can be prevented by smallpox vaccination [28].…”