Recombination of host cell mRNA with the Asia 1 foot-and-mouth disease virus genome in cell suspension culture

Zou, Xingqi; Zhu, Yuanyuan; Bao, Huang; Guo, Xiaoyu; Sun, Pu; Liu, Zaixin; Mason, Peter W.; Xu, Lu; Cui, Li; Wang, Qin; Zhu, Hongfei; Zhao, Qin

doi:10.1007/s00705-018-4008-2

Cited by 7 publications

(4 citation statements)

References 35 publications

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“…A high frequency of homologous recombination is observed by some RNA viruses in a replicative template switch mechanism. RNA‒RNA recombination has been found between viral RNAs and even between viral RNAs and host RNAs (Sztuba-Solińska, et al, 2011; Zou et al, 2019; Wang et al, 2022). Therefore, we cannot exclude the possibility that chimeric BmCPV/silkworm-BmCPV RNAs are generated by RNA recombination.…”

Section: Discussionmentioning

confidence: 99%

A novel chimeric RNA originating from BmCPV S4 andBombyx moriHDAC11 transcripts regulates virus proliferation

Pan¹,

Wei²,

Qiu³

et al. 2023

Preprint

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Polymerases encoded by segmented negative-strand RNA viruses cleave 5′-m7G-capped host transcripts to prime viral mRNA synthesis ("cap-snatching") to generate chimeric RNA, and trans-splicing occurs between viral and cellular transcripts. Bombyx mori cytoplasmic polyhedrosis virus (BmCPV), an RNA virus belonging to Reoviridae, is a major pathogen of silkworm (B. mori). The genome of BmCPV consists of 10 segmented double-stranded RNAs (S1-S10) from which viral RNAs encoding a protein are transcribed. In this study, chimeric silkworm-BmCPV RNAs, in which the sequence derived from the silkworm transcript could fuse with both the 5′ end and the 3′ end of viral RNA, were identified in the midgut of BmCPV-infected silkworms by RNA_seq and further confirmed by PCR and Sanger sequencing. A novel chimeric RNA, HDAC11-S4 RNA 4, derived from silkworm histone deacetylase 11 (HDAC11) and the BmCPV S4 transcript encoding viral structural protein 4 (VP4), was selected for validation by in situ hybridization and Northern blotting. Interestingly, our results indicated that HDAC11-S4 RNA 4 was generated in a BmCPV RNA-dependent RNA polymerase (RdRp)-independent manner and could be translated into a truncated BmCPV VP4 with a silkworm HDAC11-derived N-terminal extension. Moreover, it was confirmed that HDAC11-S4 RNA 4 inhibited BmCPV proliferation, decreased the level of H3K9me3 and increased the level of H3K9ac. These results indicated that during infection with BmCPV, a novel mechanism, different from that described in previous reports, allows the genesis of chimeric silkworm-BmCPV RNAs with biological functions.

show abstract

Section: Discussionmentioning

confidence: 99%

A novel chimeric RNA originating from BmCPV S4 andBombyx moriHDAC11 transcripts regulates virus proliferation

Pan¹,

Wei²,

Qiu³

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

“…A high frequency of homologous recombination is observed by some RNA viruses in a replicative template switch mechanism. RNA–RNA recombination has been found between viral RNAs and even between viral RNAs and host RNAs [ 42 , 43 , 44 ]. Therefore, we cannot exclude the possibility that chimeric BmCPV/silkworm-BmCPV RNAs are generated by RNA recombination.…”

Section: Discussionmentioning

confidence: 99%

A novel chimeric RNA originating from BmCPV S4 and Bombyx mori HDAC11 transcripts regulates virus proliferation

Pan,

Wei,

Qiu

et al. 2023

PLoS Pathog

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Polymerases encoded by segmented negative-strand RNA viruses cleave 5’-m7G-capped host transcripts to prime viral mRNA synthesis (“cap-snatching”) to generate chimeric RNA, and trans-splicing occurs between viral and cellular transcripts. Bombyx mori cytoplasmic polyhedrosis virus (BmCPV), an RNA virus belonging to Reoviridae, is a major pathogen of silkworm (B. mori). The genome of BmCPV consists of 10 segmented double-stranded RNAs (S1-S10) from which viral RNAs encoding a protein are transcribed. In this study, chimeric silkworm-BmCPV RNAs, in which the sequence derived from the silkworm transcript could fuse with both the 5’ end and the 3’ end of viral RNA, were identified in the midgut of BmCPV-infected silkworms by RNA_seq and further confirmed by RT-PCR and Sanger sequencing. A novel chimeric RNA, HDAC11-S4 RNA 4, derived from silkworm histone deacetylase 11 (HDAC11) and the BmCPV S4 transcript encoding viral structural protein 4 (VP4), was selected for validation by in situ hybridization and Northern blotting. Interestingly, our results indicated that HDAC11-S4 RNA 4 was generated in a BmCPV RNA-dependent RNA polymerase (RdRp)-independent manner and could be translated into a truncated BmCPV VP4 with a silkworm HDAC11-derived N-terminal extension. Moreover, it was confirmed that HDAC11-S4 RNA 4 inhibited BmCPV proliferation, decreased the level of H3K9me3 and increased the level of H3K9ac. These results indicated that during infection with BmCPV, a novel mechanism, different from that described in previous reports, allows the genesis of chimeric silkworm-BmCPV RNAs with biological functions.

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“…Recently, we developed a serum-free BHK-21 cell suspension culture platform for the production of an inactivated SVA vaccine. However, exogenous sequence insertion was observed for FMDV-infected suspension cells, suggesting that promiscuous recombination between the FMDV genome and host cell mRNA produced the recombinant virus (59). Here, the SVA recombination-deficient virus variant could be considered for a suitable vaccine seed virus to reduce the possibility of virus recombination with cellular sequence.…”

Section: Figmentioning

confidence: 99%

Senecavirus-Specific Recombination Assays Reveal the Intimate Link between Polymerase Fidelity and RNA Recombination

Wang

Shi

et al. 2019

J Virol

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Senecavirus A (SVA) is a reemerging virus, and recent evidence has emphasized the importance of SVA recombination in vivo on virus evolution. In this study, we report the development of an infectious cDNA clone for the SVA/HLJ/CHA/2016 strain. We used this strain to develop a reporter virus expressing enhanced green fluorescent protein (eGFP), which we then used to screen for a recombination-deficient SVA by an eGFP retention assay. Sequencing of the virus that retained the eGFP following passage allowed us to identify the nonsynonymous mutations (S460L alone and I212V-S460L in combination) in the RNA-dependent RNA polymerase (RdRp) region of the genome. We developed a Senecavirus-specific cell culture-based recombination assay, which we used to elucidate the role of RdRp in SVA recombination. Our results demonstrate that these two polymerase variants (S460L and I212/S460L) have reduced recombination capacity. These results indicate that the RdRp plays a central role in SVA replicative recombination. Notably, our results showed that the two recombination-deficient variants have higher replication fidelity than the wild type (WT) and display decreased ribavirin sensitivity compared to the WT. In addition, these two mutants exhibited significantly increased fitness in vitro compared to the WT. These results demonstrate that recombination and mutation rates are intimately linked. Our results have important implications for understanding the crucial role of the RdRp in virus recombination and fitness, especially in the molecular mechanisms of SVA evolution and pathogenicity. IMPORTANCE Recent evidence has emphasized the importance of SVA recombination on virus evolution in vivo. We describe the first assays to study Senecavirus A recombination. The results show that the RNA-dependent RNA polymerase plays a crucial role in recombination and that recombination can impact the fitness of SVA in cell culture. Further, SVA polymerase fidelity is closely related to recombination efficiency. The results provide key insights into the role of recombination in positive-strand RNA viruses.

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Recombination of host cell mRNA with the Asia 1 foot-and-mouth disease virus genome in cell suspension culture

Cited by 7 publications

References 35 publications

A novel chimeric RNA originating from BmCPV S4 andBombyx moriHDAC11 transcripts regulates virus proliferation

A novel chimeric RNA originating from BmCPV S4 andBombyx moriHDAC11 transcripts regulates virus proliferation

A novel chimeric RNA originating from BmCPV S4 and Bombyx mori HDAC11 transcripts regulates virus proliferation

Senecavirus-Specific Recombination Assays Reveal the Intimate Link between Polymerase Fidelity and RNA Recombination

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