Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses

Xue，Lu1; Chang，Tiancai1; Li，Zimu1,2; Wang，Chenchen3; Zhao，Heyu1; Li，Mei2; Tang，Peng1; Wen，Xin4,5; Yu，Mengmeng6; Wu，Jiqin4; Bao，Xichen1; Wang，Xiaojun6; Gong，Peng4; He，Jun1; Chen，Xinwen2,4; Xiong，Xiaoli1

2024-12-01

10.1038/s41467-024-48848-3

Nature Communications   影响因子和分区

2041-1723

Influenza viruses and thogotoviruses account for most recognized orthomyxoviruses. Thogotoviruses, exemplified by Thogoto virus (THOV), are capable of infecting humans using ticks as vectors. THOV transcribes mRNA without the extraneous 5′ end sequences derived from cap-snatching in influenza virus mRNA. Here, we report cryo-EM structures to characterize THOV polymerase RNA synthesis initiation and elongation. The structures demonstrate that THOV RNA transcription and replication are able to start with short dinucleotide primers and that the polymerase cap-snatching machinery is likely non-functional. Triggered by RNA synthesis, asymmetric THOV polymerase dimers can form without the involvement of host factors. We confirm that, distinctive from influenza viruses, THOV-polymerase RNA synthesis is weakly dependent of the host factors ANP32A/B/E in human cells. This study demonstrates varied mechanisms in RNA synthesis and host factor utilization among orthomyxoviruses, providing insights into the mechanisms behind thogotoviruses’ broad-infectivity range.

SCI

英语

其他

2-s2.0-85195005245

Scopus

1.State Key Laboratory of Respiratory Disease,Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine,Guangdong Provincial Key Laboratory of Biocomputing,GIBH-CUHK Joint Research Laboratory on Stem Cell and Regenerative Medicine,Guangzhou Institutes of Biomedicine and Health,Chinese Academy of Sciences,Guangzhou,China
2.Guangzhou National Laboratory,Guangzhou,Guangdong,China
3.College of Medicine,Southern University of Science and Technology,Shenzhen,China
4.Key Laboratory of Special Pathogens and Biosafety,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,Hubei,China
5.University of Chinese Academy of Sciences,Beijing,China
6.State Key Laboratory of Veterinary Biotechnology,Harbin Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Harbin,China

Xue，Lu,Chang，Tiancai,Li，Zimu,et al. Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses[J]. Nature Communications,2024,15(1).

Xue，Lu.,Chang，Tiancai.,Li，Zimu.,Wang，Chenchen.,Zhao，Heyu.,...&Xiong，Xiaoli.(2024).Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses.Nature Communications,15(1).

Xue，Lu,et al."Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses".Nature Communications 15.1(2024).