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Updated: Jun 7, 2025
Dissecting Host-virus Interaction in Lytic Replication of a Model Herpesvirus
Published on: October 7, 2011
Exploring the genomic basis of Mpox virus-host transmission and pathogenesis
Brayden Young1,2, Stephanie N Seifert3, Crystal Lawson1,2
1School of Molecular Biosciences, Washington State University, Pullman, Washington, USA.
Abstract:
Mpox disease, caused by the monkeypox virus (MPXV), was recently classified as a public health emergency of international concern due to its high lethality and pandemic potential. MPXV is a zoonotic disease that emerged and is primarily spread by small rodents. Historically, it was considered mainly zoonotic and not likely to sustain human-to-human transmission. However, the worldwide outbreak of Clade IIb MPXV from 2020 to 2022 and ongoing Clade I MPXV epidemics in the Democratic Republic of the Congo and surrounding areas are a warning that human-adapted MPXVs will continually arise. Understanding the viral genetic determinants of host range, pathogenesis, and immune evasion is imperative for developing control strategies and predicting the future of Mpox. Here, we delve into the MPXV genome to detail genes involved in host immune evasion strategies for this zoonotic rodent-borne and human-circulating virus. We compare MPXV gene content to related Orthopoxviruses, which have narrow host ranges, to identify potential genes involved in species-specific pathogenesis and host tropism. In addition, we cover the key virulence factor differences that distinguish the MPXV clade lineages. Finally, we dissect how genomic reduction of Orthopoxviruses, through various molecular mechanisms, is contributing to the generation of novel MPXV lineages with increased human adaptation. This review aims to highlight gene content that defines the MPXV species, MPXV clades, and novel MPXV lineages that have culminated in this virus being elevated to a public health emergency of national concern.
Insights
Mpox virus (MPXV) evolution shows genomic changes enabling increased human adaptation. Understanding these viral genetic factors is crucial for predicting future outbreaks and developing control strategies for this public health emergency.
Area of Science:
- Virology
- Genomics
- Public Health
Background:
- Mpox virus (MPXV) is a zoonotic pathogen with pandemic potential, recently declared a public health emergency.
- Historically considered zoonotic with limited human-to-human spread, MPXV outbreaks demonstrate increasing human adaptation.
- MPXV outbreaks, including Clade IIb and Clade I, highlight the emergence of human-adapted lineages.
Purpose of the Study:
- To analyze the MPXV genome for genes involved in host immune evasion.
- To compare MPXV gene content with related Orthopoxviruses to identify determinants of host tropism and pathogenesis.
- To examine virulence factor differences between MPXV clades and understand genomic reduction's role in human adaptation.
Main Methods:
- Comparative genomics of MPXV and related Orthopoxviruses.
- Analysis of viral gene content related to immune evasion and host adaptation.
- Review of molecular mechanisms driving genomic reduction and lineage evolution.
Main Results:
- Identification of specific MPXV genes contributing to immune evasion strategies.
- Discovery of potential genetic factors influencing MPXV species-specific pathogenesis and host tropism.
- Characterization of virulence differences across MPXV clades and the impact of genomic reduction on human adaptation.
Conclusions:
- Viral genomic determinants are key to MPXV's host range, pathogenesis, and immune evasion.
- Genomic reduction and evolution contribute to novel MPXV lineages with enhanced human adaptation.
- Understanding MPXV genetics is essential for predicting future epidemics and managing public health threats.
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