Transcriptional architecture of African swine fever virus
4 affiliations
- 1National Key Laboratory of Agricultural Microbiology, Hainan Research Institute, Hubei Hongshan Laboratory, College of Animal Sciences & Technology and College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China
- 2Key Laboratory of Preventive Veterinary Medicine in Hubei Province, The Cooperative Innovation Centre for Sustainable Pig Production, Wuhan, China
- 3Virology and Cell Technology Research Team, National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathum Thani, Thailand
- 4Hubei Jiangxia Laboratory, Wuhan, Hubei, China
Abstract
African swine fever virus (ASFV), a large double-stranded DNA virus, poses one of the most significant infectious disease threats to the global swine industry. ASFV transcription is particularly complex because of its unique host-independent transcription system. Using nanopore sequencing technology, we accurately identified the viral transcription start and termination sites. Combining direct RNA sequencing with experimental verification strongly supports the presence of long multicistronic RNAs. By combining this information with the viral genome annotation, we identified six novel transcriptional genes with potential functions. Furthermore, we observed transcriptional “read-through” events, in which transcription initiated at a common start site continues beyond typical termination sites, producing multiple RNA transcripts of different lengths. Additionally, via direct RNA nanopore sequencing, we identified m6A and m5C methylation modifications on viral transcripts, which are predominantly distributed at both termini of the viral genome. Compared to unmodified transcripts, modified RNAs have shorter poly(A) tails, indicating a correlation between RNA modification and poly(A) tail length. Further investigation of ASFV transcriptional architecture, “read-through” events, RNA modifications, and candidate genes may improve our understanding of the viral life cycle and pathogenicity and inform the identification of potential antiviral targets. Author summary: African swine fever virus (ASFV) causes a highly lethal disease in pigs, posing a devastating threat to the global agricultural economy. Despite its impact, how this large DNA virus orchestrates the production of its proteins during infection has remained incompletely understood. In this study, we utilized advanced sequencing technologies to comprehensively map the genetic blueprint—or “transcriptional architecture”—of ASFV. We discovered 26 potential new viral genes and revealed that the virus frequently uses an unexpectedly efficient mechanism known as “multicistronic transcription”. This indicates that a single viral RNA molecule can carry the instructions to sequentially produce multiple distinct proteins. By engineering specialized recombinant viruses with fluorescent tags, we provided strong evidence that these complex transcripts are actively translated. Furthermore, we directly detected chemical modifications (m6A and m5C) on the viral RNAs, which are concentrated in genomic regions associated with host immune evasion. Ultimately, our findings fundamentally reshape our understanding of ASFV gene expression, providing a vital foundation for discovering new antiviral targets and rationally designing vaccines.
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BibTeX
@article{wang2026transcriptional,
title = {{Transcriptional architecture of African swine fever virus}},
author = {Guiqian Wang and Pengfei Li and Xinglin He and Hua Cao and Ahmed H. Ghonaim and Shengnan Ruan and Xuexiang Yu and Jiaru Zhou and Hongmei Zhu and Mengjia Zhang and Anan Jongkaewwattana and Guiqing Peng and Qigai He and Wentao Li},
journal = {PLOS Pathogens},
year = {2026},
month = sep,
doi = {10.1371/journal.ppat.1014617},
url = {https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014617},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Transcriptional architecture of African swine fever virus
AU - Guiqian Wang
AU - Pengfei Li
AU - Xinglin He
AU - Hua Cao
AU - Ahmed H. Ghonaim
AU - Shengnan Ruan
AU - Xuexiang Yu
AU - Jiaru Zhou
AU - Hongmei Zhu
AU - Mengjia Zhang
AU - Anan Jongkaewwattana
AU - Guiqing Peng
AU - Qigai He
AU - Wentao Li
PY - 2026
DA - 2026/09/23
JO - PLOS Pathogens
DO - 10.1371/journal.ppat.1014617
UR - https://journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1014617
AB - African swine fever virus (ASFV), a large double-stranded DNA virus, poses one of the most significant infectious disease threats to the global swine industry. ASFV transcription is particularly complex because of its unique host-independent transcription system. Using nanopore sequencing technology, we accurately identified the viral transcription start and termination sites. Combining direct RNA sequencing with experimental verification strongly supports the presence of long multicistronic RNAs. By combining this information with the viral genome annotation, we identified six novel transcriptional genes with potential functions. Furthermore, we observed transcriptional “read-through” events, in which transcription initiated at a common start site continues beyond typical termination sites, producing multiple RNA transcripts of different lengths. Additionally, via direct RNA nanopore sequencing, we identified m6A and m5C methylation modifications on viral transcripts, which are predominantly distributed at both termini of the viral genome. Compared to unmodified transcripts, modified RNAs have shorter poly(A) tails, indicating a correlation between RNA modification and poly(A) tail length. Further investigation of ASFV transcriptional architecture, “read-through” events, RNA modifications, and candidate genes may improve our understanding of the viral life cycle and pathogenicity and inform the identification of potential antiviral targets. Author summary: African swine fever virus (ASFV) causes a highly lethal disease in pigs, posing a devastating threat to the global agricultural economy. Despite its impact, how this large DNA virus orchestrates the production of its proteins during infection has remained incompletely understood. In this study, we utilized advanced sequencing technologies to comprehensively map the genetic blueprint—or “transcriptional architecture”—of ASFV. We discovered 26 potential new viral genes and revealed that the virus frequently uses an unexpectedly efficient mechanism known as “multicistronic transcription”. This indicates that a single viral RNA molecule can carry the instructions to sequentially produce multiple distinct proteins. By engineering specialized recombinant viruses with fluorescent tags, we provided strong evidence that these complex transcripts are actively translated. Furthermore, we directly detected chemical modifications (m6A and m5C) on the viral RNAs, which are concentrated in genomic regions associated with host immune evasion. Ultimately, our findings fundamentally reshape our understanding of ASFV gene expression, providing a vital foundation for discovering new antiviral targets and rationally designing vaccines.
SN - 1553-7374
ER -