title: 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.
authors: Rega Institute, Laboratory of Virology and Chemotherapy, KU Leuven, Leuven, Belgium. sophie.duraffour@rega.kuleuven.be
authors: Sophie
authors: S
authors: Duraffour
authors: Barbara
authors: B
authors: Mertens
authors: Hermann
authors: H
authors: Meyer
authors: Joost J
authors: JJ
authors: van den Oord
authors: Tania
authors: T
authors: Mitera
authors: Patrick
authors: P
authors: Matthys
authors: Robert
authors: R
authors: Snoeck
authors: Graciela
authors: G
authors: Andrei
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D002460:Cell Line; D015605:Cowpox / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000821:virology*; D015608:Cowpox virus / Q000187:drug effects* / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology*; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008168:Lung / Q000473:pathology / Q000821:virology*; D051379:Mice; D010802:Phylogeny; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000998:Antiviral Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha