Elizabeth A. Falendysz
Tonie E. Rocke
Jorge E. Osorio
Juan G. Lopera
2015
<p>Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. <i>In vitro</i> and <i>in vivo</i>studies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on <i>in vitro</i> replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation <i>in vivo</i> over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.</p>
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10.1016/j.virol.2014.11.009
en
Elsevier
Attenuation of monkeypox virus by deletion of genomic regions
article