Genome-Wide Comparison of Cowpox Viruses Reveals a New Clade Related to Variola Virus

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.

Evidence of zoonotic Poxviridae coinfections in clinically diagnosed papillomas using a newly developed mini-array test

“…This virus used to be enzootic in cattle; however, such infections have not been diagnosed over the last decades, while individual cases of cowpox have been repeatedly found in cats or exotic zoo animals that were responsible for human transmission. 8,13,16,17,24,26 It is not possible to conclude that CPXV was the causal agent of the lesions reported in the domestic ruminants in our study; in fact, its low genomic load can be the result of interference caused by multiple viral agents replicating at the same time in the same target cell. On the other hand, the presence of CPXV DNA in the pathological samples of the domestic ruminants lead us to speculate that the virus may use these animal species as reservoirs to spread and persist in the environment through the scab material produced by other epitheliotropic viruses.…”

Cowpox Virus Protein CPXV012 Eludes CTLs by Blocking ATP Binding to TAP

“…6A) and make up a C-type lectin-like domain, which is suggested to be a ligand for the NK cell inhibitory receptor NKR-P1 (17). Recently, genome sequences of a number of CPXV strains from clinical isolates have been determined (38). By comparing CPXV012 homologs of these strains and of other published CPXV and orthopoxvirus strains, we identified two major clusters (Fig.…”

“…A comparison of 41 genes conserved among all known poxviruses revealed that CPXV strains group into three distinct clades (38). Members of these clades are more closely related to variola virus, camelpox virus, and taterapox virus (clade 1), CPXV (clade 2), or vaccinia virus (clade 3) (38).…”

“…Members of these clades are more closely related to variola virus, camelpox virus, and taterapox virus (clade 1), CPXV (clade 2), or vaccinia virus (clade 3) (38). All strains in clade 1 and the majority of the strains in clade 2 encode the truncated CPXV012-like protein, with the exception of the isolates CPXV GER-91 and CPXV HumLue09/1 (Fig.…”

“…Group 1 comprises the longer D10L-like proteins containing a C-type lectin-like domain, whereas group 2 contains proteins with a truncated ER-luminal domain, including CPXV012. Recently, three CPXV clades were identified based on phylogenetic analysis of 41 genes conserved in poxvirus (38). Clade 1 is closely related to variola virus, camelpox, and taterapox virus; clade 2 is a CPXV-like clade; and clade 3 is a vaccinia virus-like clade.…”