Rna Viruses Redirect Host Factors to Better Amplify Their Genome

Boguszewska-Chachulska, Anna M.; Haenni, Anne‐Lise

doi:10.1016/s0065-3527(05)65002-6

Cited by 11 publications

(5 citation statements)

References 132 publications

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“…In addition, factors affecting RNA synthesis frequently also affect translation. 117 Therefore, it becomes essential to study the role of factors in defined functional assays, such as in vitro replication or transcription systems. The purification of in vitro active CoV replication-transcription complexes (RTCs) has been described in reference 118 .…”

Section: Rna-protein Interactions Involved In Cov Rna Synthesismentioning

confidence: 99%

RNA-RNA and RNA-protein interactions in coronavirus replication and transcription

et al. 2011

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Coronavirus (CoV) RNA synthesis includes the replication of the viral genome, and the transcription of sgRNAs by a discontinuous mechanism. Both processes are regulated by RNA sequences such as the 5' and 3' untranslated regions (UTRs), and the transcription regulating sequences (TRSs) of the leader (TRS-L) and those preceding each gene (TRS-Bs). These distant RNA regulatory sequences interact with each other directly and probably through protein-RNA and protein-protein interactions involving viral and cellular proteins. By analogy to other plus-stranded RNA viruses, such as polioviruses, in which translation and replication switch involves a cellular factor (PCBP) and a viral protein (3CD) it is conceivable that in CoVs the switch between replication and transcription is also associated with the binding of proteins that are specifically recruited by the replication or transcription complexes. Complexes between RNA motifs such as TRS-L and the TRS-Bs located along the CoV genome are probably formed previously to the transcription start, and most likely promote template-switch of the nascent minus RNA to the TRS-L region. Many cellular proteins interacting with regulatory CoV RNA sequences are members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family of RNA-binding proteins, involved in mRNA processing and transport, which shuttle between the nucleus and the cytoplasm. In the context of CoV RNA synthesis, these cellular ribonucleoproteins might also participate in RNA-protein complexes to bring into physical proximity TRS-L and distant TRS-B, as proposed for CoV discontinuous transcription. In this review, we summarize RNA-RNA and RNA-protein interactions that represent modest examples of complex quaternary RNA-protein structures required for the fine-tuning of virus replication. Design of chemically defined replication and transcription systems will help to clarify the nature and activity of these structures.

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Section: Rna-protein Interactions Involved In Cov Rna Synthesismentioning

confidence: 99%

RNA-RNA and RNA-protein interactions in coronavirus replication and transcription

et al. 2011

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“…In molecular terms, how could the enhancer accelerate virus replication? It is recognized that a wide variety of host proteins, with functions not directly related to cellular RNA synthesis, are frequently associated with replication of positive-strand RNA viruses (reviewed by Lai, 1998;Boguszewska-Chachulska & Haenni, 2005), including flaviviruses (Blackwell & Brinton, 1995Ta & Vrati, 2000;De Nova Ocampo et al, 2002). These are often identified as proteins with RNA-binding and trafficking activities.…”

Section: §Utr Alignment Of All Mbfv Subgroupsmentioning

confidence: 99%

Direct repeats in the 3′ untranslated regions of mosquito-borne flaviviruses: possible implications for virus transmission

Грицун

Gould

2006

Journal of General Virology

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Direct repeats (DRs) of 20-45 nucleotide conserved sequences (CS) and repeated CS (RCS), separated by non-conserved sequences up to 100 nucleotides long, were previously described in the 39 untranslated region (39UTR) of the three major mosquito-borne flavivirus (MBFV) subgroups, represented by Japanese encephalitis virus, Yellow fever virus and Dengue virus. Each subgroup exhibits a specific pattern of DRs, the biological significance of which has not yet been adequately addressed. The DRs were originally identified using conventional alignment programs based on the assumption that genetic variation is driven primarily by nucleotide substitutions. Since there are no recognized alignment programs that can adequately accommodate very divergent sequences, a method has been devised to construct and analyse a substantially improved 39UTR alignment between these highly divergent viruses, based on the concept that deletions and/or insertions, in addition to substitutions, are important drivers of 39UTR evolution. This 'robust alignment' approach demonstrated more extensive homologies in the 39UTR than had been recognized previously and revealed the presence of similar DRs, either intact or as sequence 'remnants', in all the MBFV subgroups. The relevance of these observations is discussed in relation to (i) the function of DRs as elements of replication enhancement, (ii) the evolution of RNA secondary structures and (iii) the significance of DRs and secondary structures in MBFV transmissibility between vertebrate and invertebrate hosts.

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“… 6 – 10 In contrast, interactions between host proteins and viral RNA (vRNA) are much less well understood, despite the known importance of the viral RNA genome for multiple processes during infection, including viral genome translation and replication. 11 Recent years have seen an explosion in high-throughput methods that enable global analyses of RNA–protein interactions (“the interactome”) in cells. 12 , 13 These approaches can substantially advance our understanding of the infection and pathology of RNA viruses and can inform diverse and effective therapeutic options.…”

Section: Introductionmentioning

confidence: 99%

Comparison of viral RNA–host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2

et al. 2021

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In contrast to the extensive research about viral protein–host protein interactions that has revealed major insights about how RNA viruses engage with host cells during infection, few studies have examined interactions between host factors and viral RNAs (vRNAs). Here, we profiled vRNA–host protein interactomes for three RNA virus pathogens (SARS-CoV-2, Zika, and Ebola viruses) using ChIRP-MS. Comparative interactome analyses discovered both common and virus-specific host responses and vRNA-associated proteins that variously promote or restrict viral infection. In particular, SARS-CoV-2 binds and hijacks the host factor IGF2BP1 to stabilize vRNA and augment viral translation. Our interactome-informed drug repurposing efforts identified several FDA-approved drugs (e.g., Cepharanthine) as broad-spectrum antivirals in cells and hACE2 transgenic mice. A co-treatment comprising Cepharanthine and Trifluoperazine was highly potent against the newly emerged SARS-CoV-2 B.1.351 variant. Thus, our study illustrates the scientific and medical discovery utility of adopting a comparative vRNA–host protein interactome perspective.

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Rna Viruses Redirect Host Factors to Better Amplify Their Genome

Cited by 11 publications

References 132 publications

RNA-RNA and RNA-protein interactions in coronavirus replication and transcription

RNA-RNA and RNA-protein interactions in coronavirus replication and transcription

Direct repeats in the 3′ untranslated regions of mosquito-borne flaviviruses: possible implications for virus transmission

Comparison of viral RNA–host protein interactomes across pathogenic RNA viruses informs rapid antiviral drug discovery for SARS-CoV-2

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