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Research Project: Viral Ecology of Henipaviruses in Endemic Settings and Intervention Strategies to Prevent their Spread to Domestic Animals

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Title: Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018-2024: Predominance of zoonotic transmission

Author
item Hensley, Lisa
item KINGANDA-LUSAMAKI, EDDY - Institute National Research Biomedical
item AMURI-AZIZA, ADRIENNE - Institute National Research Biomedical
item FERNANDEZ-NUNEZ, NICOLAS - University Of Montpellier
item MAKANGARA-CIGOLO, JEAN-CLAUDE - Institute National Research Biomedical
item PRATT, CATHERINE - Biosurv International
item HASIVIRWE VAKANIAKI, EMMANUEL - Institute National Research Biomedical
item HOFF, NICOLE - University Of California (UCLA)
item LUKANDA-NDELEMO, GRADI - Institute National Research Biomedical
item AKIL-BANDALI, PRINCE - Institute National Research Biomedical
item SABITI NUNDU, SABIN - Institute National Research Biomedical
item MULOPO-MUKANYA, NOELLA - Institute National Research Biomedical
item NGIMBA, MICHEL - Institute National Research Biomedical
item MODADRA-MADAKPA, BRIGITTE - Institute National Research Biomedical
item DIAVITA, RUTH - Institute National Research Biomedical
item PAKU-TSHAMBU, PRINCESSE - Institute National Research Biomedical
item PUKUTA-SIMBU, ELISABETH - Institute National Research Biomedical
item MERRITT, SYDNEY - University Of California (UCLA)
item O'TOOLE, AINE - University Of Edinburgh
item LOW, NICOLA - University Of Bern
item NKUBA-NDAYE, ANTONIE - Institute National Research Biomedical
item KAVUNGA-MEMBO, HUGO - Institute National Research Biomedical
item SHONGO LUSHIMA, ROBERT - Ministry Of Public Health
item LIESENBORGHS, LAURENS - Institute Of Tropical Medicine
item WAWINA-BOKALANGA, TONY - Institute National Research Biomedical
item VERCAUTEREN, KOEN - Institute Of Tropical Medicine
item MUKADI-BAMULEKA, DANIEL - Institute National Research Biomedical
item SUBISSI, LORENZO - World Health Organization (WHO) - Switzerland
item MUYEMBE-TAMFUM, JEAN-JACQUES - Institute National Research Biomedical
item KINDRACHUK, JASON - University Of Manitoba
item AYOUBA, AHIDJO - University Of Montpellier
item RAMBAUT, ANDREW - University Of Edinburgh
item DELAPORTE, ERIC - University Of Montpellier
item TESSEMA, SOFONIAS - Africa Center For Disease Control And Prevention (CDC)
item D'ORTENZIO, ERIC - Anrs Emerging Infectious Diseases Agency (ANRS MIE)
item RIMOIN, ANNE - University Of California (UCLA)
item MBALA-KINGEBENI, PLACIDE - Institute National Research Biomedical
item PEETERS, MARTINE - University Of Montpellier
item AHUKA-MUNDEKE, STEVE - Institute National Research Biomedical

Submitted to: Cell
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/3/2024
Publication Date: 1/9/2025
Citation: Hensley, L.E., Kinganda-Lusamaki, E., Amuri-Aziza, A., Fernandez-Nunez, N., Makangara-Cigolo, J., Pratt, C., Hasivirwe Vakaniaki, E., Hoff, N.A., Lukanda-Ndelemo, G., Akil-Bandali, P., Sabiti Nundu, S., Mulopo-Mukanya, N., Ngimba, M., Modadra-Madakpa, B., Diavita, R., Paku-Tshambu, P., Pukuta-Simbu, E., Merritt, S., O'Toole, A., Low, N., Nkuba-Ndaye, A., Kavunga-Membo, H., Shongo Lushima, R., Liesenborghs, L., Wawina-Bokalanga, T., Vercauteren, K., Mukadi-Bamuleka, D., Subissi, L., Muyembe-Tamfum, J., Kindrachuk, J., Ayouba, A., Rambaut, A., Delaporte, E., Tessema, S., D'Ortenzio, E., Rimoin, A.W., Mbala-Kingebeni, P., Peeters, M., Ahuka-Mundeke, S. 2025. Clade I mpox virus genomic diversity in the Democratic Republic of the Congo, 2018-2024: Predominance of zoonotic transmission. Cell. 188(1). Article 4-14.e6. https://doi.org/10.1016/j.cell.2024.10.017.
DOI: https://doi.org/10.1016/j.cell.2024.10.017

Interpretive Summary: Mpox virus (MPXV) is the causative agent of mpox disease. In the Democratic Republic of the Congo, recent developments in the changing epidemiology, transmission and case load are of particular concern. We sought to evaluate the changing genomic signature of the mpox virus over the 2018-2024 period. By sequencing genomes from samples collected from 337 patients across the country, we show an evolving virus which has been changing with APOBEC3 mutations linked to human adaptation. We also show the divergence of subclade Ib in South Kivu province, as well as high diversity of the virus across the country. Due to the nature of the virus, these findings further emphasize the importance of genomic analysis to best track and understand an ever-changing biologic threat.

Technical Abstract: Recent reports raise concerns on the changing epidemiology of mpox in the Democratic Republic of the Congo (DRC). High-quality genomes were generated for 337 patients from 14/26 provinces to document whether the increase in number of cases is due to zoonotic spillover events or viral evolution, with enrichment of APOBEC3 mutations linked to human adaptation. Our study highlights two patterns of transmission contributing to the source of human cases. All new sequences from the eastern South Kivu province (n = 17; 4.8%) corresponded to the recently described clade Ib, associated with sexual contact and sustained human-to-human transmission. By contrast, all other genomes are clade Ia, which exhibits high genetic diversity with low numbers of APOBEC3 mutations compared with clade Ib, suggesting multiple zoonotic introductions. The presence of multiple clade I variants in urban areas highlights the need for coordinated international response efforts and more studies on the transmission and the reservoir of mpox.