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Insights about the evolutionary mechanisms of poxviruses: Myxoma virus in Lepus, a case study

07 Jan 2022 - Ana Águeda Pinto, BIOPOLIS, CIBIO-InBIO/UP | 14h30
Insights about the evolutionary mechanisms of poxviruses: Myxoma virus in Lepus, a case study

Myxoma virus (MYXV) is naturally found in rabbit Sylvilagus species, and is known to cause the lethal myxomatosis in European rabbits (Oryctolagus cuniculus). In 2019, a MYXV strain (MYXV-Tol) causing a myxomatosis-like disease in Iberian hares (Lepus granatensis) was identified. MYXV-Tol acquired a recombinant region of ~2.8kb encoding for several new genes, including a novel host range gene (M159) that we show to be an orthologous member of the vaccinia C7 host range family. Here, to test whether M159 alone has enabled MYXV to alter its host range to Iberian hares, several recombinant viruses were generated, including a MYXV-Tol ΔM159 (knockout). While MYXV-Tol underwent fully productive infection in hare cells, neither wild-type MYXV-Lau strain (lacking M159) or vMyxTol-ΔM159 (deleted for M159) were able to infect and replicate, showing that the ability of MYXV-Tol to infect hare cells and replicate depends on the presence of M159 gene. Similar to other C7L family members, M159 was shown to be expressed as an early/late gene but was translocated into the nucleus at later time points, indicating further studies are needed to elucidate its role in the nucleus. Finally, in rabbit cells, M159 protein did not contribute to increased replication, but was able to upregulate the replication levels of MYXV in non-permissive and semi-permissive human cancer cells, suggesting that the M159 targeted pathway is conserved across mammalian species. Altogether, these observations demonstrate that M159 protein plays a critical role in determining the host specificity of MYXV-Tol in hare and human cells by imparting new host range functions.

Ana Pinto is a 4th-year BIODIV PhD student, working under the supervision of Pedro Esteves (CIBIO-InBIO, UP). She graduated in Biology in the University of Porto, Portugal and holds a MSc in Molecular and Cellular Biology from the University of Porto. Currently she is interested in investigate the biological underpinnings driving Myxoma virus adaptation and disease manifestation in hares following a species jump from rabbits.

[Host: Pedro José Esteves, Immunity and Emerging Diseases - IMED]

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