Monkeypox virus genomic accordion strategies

Sara Monzón, Sarai Varona, Anabel Negredo, Santiago Vidal-Freire, Juan Angel Patiño-Galindo, Natalia Ferressini-Gerpe, Angel Zaballos, Eva Orviz, Oskar Ayerdi, Ana Muñoz-Gómez, Alberto Delgado-Iribarren, Vicente Estrada, Cristina García, Francisca Molero, Patricia Sánchez-Mora, Montserrat Torres, Ana Vázquez, Juan-Carlos Galán, Ignacio Torres, Manuel Causse del Río, Laura Merino-Diaz, Marcos López, Alicia Galar, Laura Cardeñoso, Almudena Gutiérrez, Cristina Loras, Isabel Escribano, Marta E. Alvarez-Argüelles, Leticia Río, María Simón, María Angeles Meléndez, Juan Camacho, Laura Herrero, Pilar Jiménez, María Luisa Navarro-Rico, Isabel Jado, Elaina Giannetti, Jens H. Kuhn, Mariano Sanchez-Lockhart, Nicholas Paola, Jeffrey R. Kugelman, Susana Guerra, Adolfo García-Sastre, Isabel Cuesta, Maripaz P. Sánchez-Seco and Gustavo Palacios ()
Additional contact information
Sara Monzón: Instituto de Salud Carlos III
Sarai Varona: Instituto de Salud Carlos III
Anabel Negredo: Instituto de Salud Carlos III
Santiago Vidal-Freire: Icahn School of Medicine at Mount Sinai
Juan Angel Patiño-Galindo: Icahn School of Medicine at Mount Sinai
Natalia Ferressini-Gerpe: Icahn School of Medicine at Mount Sinai
Angel Zaballos: Instituto de Salud Carlos III
Eva Orviz: Hospital Clínico San Carlos
Oskar Ayerdi: Hospital Clínico San Carlos
Ana Muñoz-Gómez: Hospital Clínico San Carlos
Alberto Delgado-Iribarren: Hospital Clínico San Carlos
Vicente Estrada: Instituto de Salud Carlos III
Cristina García: Instituto de Salud Carlos III
Francisca Molero: Instituto de Salud Carlos III
Patricia Sánchez-Mora: Instituto de Salud Carlos III
Montserrat Torres: Instituto de Salud Carlos III
Ana Vázquez: Instituto de Salud Carlos III
Juan-Carlos Galán: Instituto de Salud Carlos III
Ignacio Torres: Instituto de Investigación INCLIVA
Manuel Causse del Río: Instituto Maimónides de Investigación Biomédica de Córdoba
Laura Merino-Diaz: Hospital Universitario Virgen del Rocío
Marcos López: Hospital Universitario Puerta de Hierro Majadahonda
Alicia Galar: Hospital General Universitario Gregorio Marañón
Laura Cardeñoso: Hospital Universitario de la Princesa
Almudena Gutiérrez: Hospital Universitario La Paz
Cristina Loras: Hospital General y Universitario
Isabel Escribano: Hospital General Universitario Dr. Balmis
Marta E. Alvarez-Argüelles: Hospital Universitario Central de Asturias
Leticia Río: Hospital Quironsalud Torrevieja
María Simón: Hospital Central de la Defensa “Gómez Ulla”
María Angeles Meléndez: Hospital Universitario 12 de Octubre
Juan Camacho: Instituto de Salud Carlos III
Laura Herrero: Instituto de Salud Carlos III
Pilar Jiménez: Instituto de Salud Carlos III
María Luisa Navarro-Rico: Instituto de Salud Carlos III
Isabel Jado: Instituto de Salud Carlos III
Elaina Giannetti: Icahn School of Medicine at Mount Sinai
Jens H. Kuhn: Fort Detrick
Mariano Sanchez-Lockhart: Fort Detrick
Nicholas Paola: Fort Detrick
Jeffrey R. Kugelman: Fort Detrick
Susana Guerra: Icahn School of Medicine at Mount Sinai
Adolfo García-Sastre: Icahn School of Medicine at Mount Sinai
Isabel Cuesta: Instituto de Salud Carlos III
Maripaz P. Sánchez-Seco: Instituto de Salud Carlos III
Gustavo Palacios: Icahn School of Medicine at Mount Sinai

Nature Communications, 2024, vol. 15, issue 1, 1-18

Abstract: Abstract The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome’s low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established “genomic accordion” evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Date: 2024
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DOI: 10.1038/s41467-024-46949-7

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