Characterization of ATI, TK and IFN-alpha/beta R genes in the genome of the BeAn 58058 virus, a naturally attenuated wild Orthopoxvirus

The lack of knowledge about the natural host of Vaccinia virus (VV) along w ith the description of human infections caused by poxviruses after smallpox eradication has increased the need to characterize poxviruses isolated fro m the wild. Moreover, in the past years poxviruses have been widely studied as potential vaccination tools, with the discovery of several genes implic ated in the evasion of the host immune response involved in virus pathogene sis. Among them, an Interferon (IFN)-binding protein was identified in the supernatant of VV strain WR infected cells coded by the B18R gene. It was s hown that many other Orthopoxviruses also encode and express this soluble r eceptor although some VV strains such as Lister and modified Ankara, which were less reactogenic vaccines, do not. The BeAn 58058 virus (BAV) has been recently characterized and proposed to be an Orthopoxvirus. BAV was also s hown to be less virulent in animal models than VV Lister. Here we report th e identification of an IFN-alpha/betaR gene in the BAV genome with 99% of s equence identity with the VVWR B18R gene. The identified gene encodes a B18 R-like IFN binding protein as demonstrated by its capacity to inhibit the I FN-mediated protection of VERO cells against EMC virus. In order to better characterize the virus we have searched for the A type inclusion body (ATI) gene currently used in the classification of Orthopoxviruses but did not d etect it in the BAV genome. We have also sequenced the BAV thymidine kinase (TK) gene, a poxvirus-conserved gene, which, as expected, showed high homo logy with the TK gene of other poxviruses. Phylogenetic trees were construc ted based on sequences of the IFN-alpha/betaR and TK genes from several pox viruses and in both cases BAV was placed in the same cluster as other VV st rains. These observations strengthened the hypothesis that this virus is a variant of the VV vaccine used in Brazil. However the explanation for the B AV lack of virulence remains to be discovered.