2026-10-12T04:30:32Z https://www.scidb.cn/oai

10.57760/sciencedb.32536 2026-08-28T11:23:42Z

2026-08-28 The 5-methylcytosine modification in the PB2 cRNA of influenza virus impairs viral RNA replication and attenuates pathogenicity doi:10.57760/sciencedb.32536 en As a pivotal epigenetic modification, 5-methylcytosine (m5C) play a significant role in RNA stability, translation regulation, and cellular metabolism. Growing evidence suggests that m5C methylation is involved in the regulation of virus-host interactions. However, its function during influenza virus infections remains elusive. Here, we demonstrate for the first time that m5C methylation of the influenza virus PB2 gene, encoding a core polymerase subunit, acts as a negative regulator of viral infection. Loss of m5C modification in PB2 complementary RNA (cRNA) enhances its transcription and slows its degradation rate, facilitates polymerase binding to RNA, and promotes viral genomic RNA synthesis. The subsequent accumulation of RNA and polymerase proteins accelerates the nuclear export of viral ribonucleoprotein complexes, enhances progeny virion assembly and maturation, and ultimately leads to enhanced viral pathogenicity. Our findings reveal a novel mechanism by which m5C methylation fine-tunes influenza virus replication by suppressing viral RNA synthesis, and provide evidence for a previously unrecognized antiviral strategy centered on m5C-mediated epitranscriptomic regulation. influenza virus; m5C modification; RNA replication; viral pathogenicity; PB2 cRNA Wanling You Xiaojie Shi Weixing Du Aohua Geng Siqi Zhou Shuhui Deng Jinglan Yang Xiao Xiao Xiuli Wei Tingting Xiang Yirong Wang Hongying Chen Yinjie Lian Long Liu PUBLIC https://creativecommons.org/licenses/by/4.0/ dataset Science Data Bank