Comparative Pathogenesis,Genomics and Phylogeography of Mousepox |
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Authors: | Carla Mavian Alberto Lpez-Bueno Rocío Martín Andreas Nitsche Antonio Alcamí |
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Institution: | 1.Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Campus de Cantoblanco, Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049 Madrid, Spain; (C.M.); (A.L.-B.); (R.M.);2.Centre for Biological Threats and Special Pathogens, Highly Pathogenic Viruses (ZBS1), Robert Koch Institute, 13353 Berlin, Germany; |
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Abstract: | Ectromelia virus (ECTV), the causative agent of mousepox, has threatened laboratory mouse colonies worldwide for almost a century. Mousepox has been valuable for the understanding of poxvirus pathogenesis and immune evasion. Here, we have monitored in parallel the pathogenesis of nine ECTVs in BALB/cJ mice and report the full-length genome sequence of eight novel ECTV isolates or strains, including the first ECTV isolated from a field mouse, ECTV-MouKre. This approach allowed us to identify several genes, absent in strains attenuated through serial passages in culture, that may play a role in virulence and a set of putative genes that may be involved in enhancing viral growth in vitro. We identified a putative strong inhibitor of the host inflammatory response in ECTV-MouKre, an isolate that did not cause local foot swelling and developed a moderate virulence. Most of the ECTVs, except ECTV-Hampstead, encode a truncated version of the P4c protein that impairs the recruitment of virions into the A-type inclusion bodies, and our data suggest that P4c may play a role in viral dissemination and transmission. This is the first comprehensive report that sheds light into the phylogenetic and geographic relationship of the worldwide outbreak dynamics for the ECTV species. |
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Keywords: | mousepox poxvirus pathogenesis genome sequence virulence A-type inclusion bodies |
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