Mary Wilson
Well-known member
Posted September 30, 2022.
doi: https://doi.org/10.1101/2022.09.30.510261
Sara Monzon, Sarai Varona, Anabel Negredo, Juan Angel Patiño-Galindo, Santiago Vidal-Freire, Angel Zaballos, Eva Orviz, Oskar Ayerdi, Ana Muñoz-Garcia, Alberto Delgado-Iribarren, Vicente Estrada, Cristina Garcia, Francisca Molero, Patricia Sanchez, Montserrat Torres, Ana Vazquez, Juan-Carlos Galan, Ignacio Torres, Manuel Causse del Rio, Laura Merino, Marcos Lopez, Alicia Galar, Laura Cardeñoso, Almudena Gutierrez, Juan Camacho, Laura Herrero, Pilar Jimenez-Sancho, Maria Luisa Navarro-Rico, Isabel Jado, Jens Kuhn, Mariano Sanchez-Lockhart, Nicholas Di Paola, Jeffrey R. Kugelman, Elaina Giannetti, Susana Guerra, Adolfo Garcia-Sastre, Gustavo Palacios, Maripaz Sanchez-Seco, Isabel Cuesta
Abstract
The recent outbreak of Monkeypox displays novel transmission features. The circulating strain is a descendant of a lineage that had been circulating in Nigeria since 2017. The prognosis of monkeypox disease (MPX) with the circulating strain is generally good but the estimated primary reproduction number (R0) among men who have sex with men (MSM) was above 1 suggesting efficient person-to-person transmission. Different mechanisms of viral entry and egress, as well as virus-coded host factors, are the main biological determinants of poxvirus transmissibility. OPXV evolution is driven by gene loss of virus-host interacting genes and selective pressure from host species using unique adaptive strategies at the gene and nucleotide level.
In this context, we evaluated the effects of genomic instability in low-complexity-regions, areas that are often neglected during sequencing, during the early stage of the outbreak in Madrid, Spain. We uncovered significant variation in short-tandem repeat areas of the MPXV genome that could be associated with changes in transmissibility. Expression, translation, stability, or function of OPG153 (VACV A26L), OPG204 (VACV B16R) and OPG208 (VACV B19R) could be affected by the changes, in a manner that is consistent with proven genomic accordion strategies of OPXV evolution. Intriguingly, while the changes observed in OPG153 stand out as they are located inside a region under high selective pressure for transmission, in a gene that is clearly considered a core gene involved in attachment and egress; the changes in OPG208, a serine protease inhibitor-like protein that has been identified as an apoptosis inhibitor, host-range factor and virulence factor; and OPG204, a known inhibitor of the Type I interferon system shown to act as a decoy receptor, could also explain phenotypic changes. Further functional studies to complement this comparative genomic study are urgently needed.
https://www.biorxiv.org/content/10.1101/2022.09.30.510261v1.full.pdf
doi: https://doi.org/10.1101/2022.09.30.510261
Sara Monzon, Sarai Varona, Anabel Negredo, Juan Angel Patiño-Galindo, Santiago Vidal-Freire, Angel Zaballos, Eva Orviz, Oskar Ayerdi, Ana Muñoz-Garcia, Alberto Delgado-Iribarren, Vicente Estrada, Cristina Garcia, Francisca Molero, Patricia Sanchez, Montserrat Torres, Ana Vazquez, Juan-Carlos Galan, Ignacio Torres, Manuel Causse del Rio, Laura Merino, Marcos Lopez, Alicia Galar, Laura Cardeñoso, Almudena Gutierrez, Juan Camacho, Laura Herrero, Pilar Jimenez-Sancho, Maria Luisa Navarro-Rico, Isabel Jado, Jens Kuhn, Mariano Sanchez-Lockhart, Nicholas Di Paola, Jeffrey R. Kugelman, Elaina Giannetti, Susana Guerra, Adolfo Garcia-Sastre, Gustavo Palacios, Maripaz Sanchez-Seco, Isabel Cuesta
Abstract
The recent outbreak of Monkeypox displays novel transmission features. The circulating strain is a descendant of a lineage that had been circulating in Nigeria since 2017. The prognosis of monkeypox disease (MPX) with the circulating strain is generally good but the estimated primary reproduction number (R0) among men who have sex with men (MSM) was above 1 suggesting efficient person-to-person transmission. Different mechanisms of viral entry and egress, as well as virus-coded host factors, are the main biological determinants of poxvirus transmissibility. OPXV evolution is driven by gene loss of virus-host interacting genes and selective pressure from host species using unique adaptive strategies at the gene and nucleotide level.
In this context, we evaluated the effects of genomic instability in low-complexity-regions, areas that are often neglected during sequencing, during the early stage of the outbreak in Madrid, Spain. We uncovered significant variation in short-tandem repeat areas of the MPXV genome that could be associated with changes in transmissibility. Expression, translation, stability, or function of OPG153 (VACV A26L), OPG204 (VACV B16R) and OPG208 (VACV B19R) could be affected by the changes, in a manner that is consistent with proven genomic accordion strategies of OPXV evolution. Intriguingly, while the changes observed in OPG153 stand out as they are located inside a region under high selective pressure for transmission, in a gene that is clearly considered a core gene involved in attachment and egress; the changes in OPG208, a serine protease inhibitor-like protein that has been identified as an apoptosis inhibitor, host-range factor and virulence factor; and OPG204, a known inhibitor of the Type I interferon system shown to act as a decoy receptor, could also explain phenotypic changes. Further functional studies to complement this comparative genomic study are urgently needed.
https://www.biorxiv.org/content/10.1101/2022.09.30.510261v1.full.pdf