Abstract
Zoonotic infections caused by several orthopoxviruses (OPV) like monkeypox virus or vaccinia virus have a significant impact on human health. In Europe, the number of diagnosed infections with cowpox viruses (CPXV) is increasing in animals as well as in humans. CPXV used to be enzootic in cattle; however, such infections were not being diagnosed over the last decades. Instead, individual cases of cowpox are being found in cats or exotic zoo animals that transmit the infection to humans. Both animals and humans reveal local exanthema on arms and legs or on the face. Although cowpox is generally regarded as a self-limiting disease, immunosuppressed patients can develop a lethal systemic disease resembling smallpox. To date, only limited information on the complex and, compared to other OPV, sparsely conserved CPXV genomes is available. Since CPXV displays the widest host range of all OPV known, it seems important to comprehend the genetic repertoire of CPXV which in turn may help elucidate specific mechanisms of CPXV pathogenesis and origin. Therefore, 22 genomes of independent CPXV strains from clinical cases, involving ten humans, four rats, two cats, two jaguarundis, one beaver, one elephant, one marah and one mongoose, were sequenced by using massive parallel pyrosequencing. The extensive phylogenetic analysis showed that the CPXV strains sequenced clearly cluster into several distinct clades, some of which are closely related to Vaccinia viruses while others represent different clades in a CPXV cluster. Particularly one CPXV clade is more closely related to Camelpox virus, Taterapox virus and Variola virus than to any other known OPV. These results support and extend recent data from other groups who postulate that CPXV does not form a monophyletic clade and should be divided into multiple lineages.
Highlights
Variola virus (VARV) was one of the most lethal viruses known to humankind with an estimated total death toll of 300– 500 million
The examination of complete genomes provides more detailed insight into phylogenetic relations of pathogens compared to previous studies that usually had been restricted to the analysis of short genomic regions
We analyzed phylogenetic relations of OPV by adding the full genome sequences of 22 newly isolated cowpox virus (CPXV) strains to the 93 OPV full genome sequences that became publicly available recently, 12 sequences of which were CPXV
Summary
Variola virus (VARV) was one of the most lethal viruses known to humankind with an estimated total death toll of 300– 500 million. Owing to its narrow host range which only allowed infection of humans, VARV could be eradicated in a large-scale vaccination effort initiated by the WHO in 1967. The last known natural case of smallpox occurred in 1977 [1]. Based upon Edward Jenner’s discovery of the protective effect against VARV infection mediated by a poxvirus containing material taken from cows, which is generally assumed to contain cowpox virus (CPXV), live CPXV was considered to have been used initially as vaccine. The far less virulent Vaccinia virus (VACV) was used. The evolutionary relationship between VARV, VACV and CPXV is still unclear
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