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Volume 18
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10.3390/v18020211
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This is an early access version, the complete PDF, HTML, and XML versions will be available soon.
Article

A Unified Framework to Prioritize RNA Virus Cross-Species Transmission Risk Across an Expansive Host Landscape

by
Di Zhao
1,2,
Yi-Fei Wang
1,
Zu-Fei Yin
3,
Ya-Fei Wu
4,
Hui-Jun Yu
1,2,
Luo-Yuan Xia
2,
Xiao-He Liu
2,
Xiao-Ming Cui
2,
Xiao-Yu Shi
2,
Dai-Yun Zhu
2,
Na Jia
2,
Jia-Fu Jiang
2,
Wu-Chun Cao
1,2,* and
Wenqiang Shi
2,*
1
Institute of EcoHealth, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, China
2
State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Science, Beijing 100071, China
3
School of Public Health, Nanjing Medical University, Nanjing 211166, China
4
National Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100071, China
*
Authors to whom correspondence should be addressed.
Viruses 2026, 18(2), 211; https://doi.org/10.3390/v18020211
Submission received: 6 January 2026 / Revised: 29 January 2026 / Accepted: 3 February 2026 / Published: 5 February 2026
(This article belongs to the Section General Virology)
Review Reports Versions Notes

Abstract

RNA viruses exhibit high mutation rates and strong host adaptive capacity, posing major public health challenges. Although meta-transcriptomic studies have uncovered vast numbers of novel RNA viral sequences, identifying those with spillover risks remains difficult. Current virus host-prediction methods can only predict a narrow set of host labels at coarse taxonomic levels (e.g., kingdom or order), which hampers precise evaluation of cross-species transmission risk and may overlook potential zoonotic hosts. To overcome these limitations, we developed UniVH, a unified virus–host association prediction framework trained on an exceptionally broad spectrum of 90 viral families and 240 host families, enabling robust prediction even for phylogenetically distant or data-scarce hosts. UniVH achieved a host prediction accuracy of 71.2% for novel viruses discovered after 2020, representing a 15.3% improvement over conventional BLASTp-based homology approaches. Feature interpretation revealed that viral structural genes and host immune- and metabolism-related genes contributed most significantly to predictive performance. Model predictions indicated widespread host-range expansion, with 20 mammalian virus families doubling their documented mammalian host ranges and several showing marked increases in viruses with human-infection potential. This unified, interpretable framework represents an important methodological advance for future RNA virus spillover-risk evaluation and emerging virus prioritization.
Keywords: RNA viruses; host prediction; genomic language model; virus–host interaction; cross-species transmission RNA viruses; host prediction; genomic language model; virus–host interaction; cross-species transmission

Share and Cite

MDPI and ACS Style

Zhao, D.; Wang, Y.-F.; Yin, Z.-F.; Wu, Y.-F.; Yu, H.-J.; Xia, L.-Y.; Liu, X.-H.; Cui, X.-M.; Shi, X.-Y.; Zhu, D.-Y.; et al. A Unified Framework to Prioritize RNA Virus Cross-Species Transmission Risk Across an Expansive Host Landscape. Viruses 2026, 18, 211. https://doi.org/10.3390/v18020211

AMA Style

Zhao D, Wang Y-F, Yin Z-F, Wu Y-F, Yu H-J, Xia L-Y, Liu X-H, Cui X-M, Shi X-Y, Zhu D-Y, et al. A Unified Framework to Prioritize RNA Virus Cross-Species Transmission Risk Across an Expansive Host Landscape. Viruses. 2026; 18(2):211. https://doi.org/10.3390/v18020211

Chicago/Turabian Style

Zhao, Di, Yi-Fei Wang, Zu-Fei Yin, Ya-Fei Wu, Hui-Jun Yu, Luo-Yuan Xia, Xiao-He Liu, Xiao-Ming Cui, Xiao-Yu Shi, Dai-Yun Zhu, and et al. 2026. "A Unified Framework to Prioritize RNA Virus Cross-Species Transmission Risk Across an Expansive Host Landscape" Viruses 18, no. 2: 211. https://doi.org/10.3390/v18020211

APA Style

Zhao, D., Wang, Y.-F., Yin, Z.-F., Wu, Y.-F., Yu, H.-J., Xia, L.-Y., Liu, X.-H., Cui, X.-M., Shi, X.-Y., Zhu, D.-Y., Jia, N., Jiang, J.-F., Cao, W.-C., & Shi, W. (2026). A Unified Framework to Prioritize RNA Virus Cross-Species Transmission Risk Across an Expansive Host Landscape. Viruses, 18(2), 211. https://doi.org/10.3390/v18020211

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