RNA virus infections and their effect on host alternative splicing

Sehrawat, Sapna; García-Blanco, Mariano A.

doi:10.1016/j.antiviral.2022.105503

Cited by 5 publications

(1 citation statement)

References 46 publications

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“…Functionally, AS events are deeply involved in many biological and pathological processes, such as sex determination [ 15 ], organ development [ 16 ], cancer occurrence [ 17 ], and even virus infection [ 18 ]. Based on the facts that virus unscrupulously disrupts cellular pathways and splicing process is a ubiquitous regulatory mechanism of gene expression, AS is undoubtedly deeply involved in virus infection.…”

Section: Introductionmentioning

confidence: 99%

Virus usurps alternative splicing to clear the decks for infection

Gao

Chen

et al. 2023

Virol J

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Since invasion, there will be a tug-of-war between host and virus to scramble cellular resources, for either restraining or facilitating infection. Alternative splicing (AS) is a conserved and critical mechanism of processing pre-mRNA into mRNAs to increase protein diversity in eukaryotes. Notably, this kind of post-transcriptional regulatory mechanism has gained appreciation since it is widely involved in virus infection. Here, we highlight the important roles of AS in regulating viral protein expression and how virus in turn hijacks AS to antagonize host immune response. This review will widen the understandings of host-virus interactions, be meaningful to innovatively elucidate viral pathogenesis, and provide novel targets for developing antiviral drugs in the future.

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Section: Introductionmentioning

confidence: 99%

Virus usurps alternative splicing to clear the decks for infection

Gao

Chen

et al. 2023

Virol J

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Serine-arginine protein kinases and their targets in viral infection and their inhibition

Zheng

Ren

Wang

2023

Cell. Mol. Life Sci.

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Zika and Dengue Viruses Differentially Modulate Host mRNA Processing Factors Defining Its Virulence

Scholl,

Gong,

et al. 2024

Preprint

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Rising global temperatures coupled with increasing international travel, and trade are contributing to spread of vectors such as ticks and mosquitoes, resulting in a surge of vector-borne flavivirus infection in human population. Furthermore, this increase in flavivirus infection pose threat to the safety of biologics such as cell and gene therapy products as human-derived materials are commonly used during manufacturing of these drug products. In this study, we conducted time-course transcriptomic and protein analyses to uncover the host molecular factors driving the virulence of Zika virus (ZIKV) and Dengue virus (DENV) in the context of host defense mechanisms, as these two viruses have caused the most recent and significant flavivirus outbreaks. Compared to DENV, ZIKV exhibited stronger virulence and cytopathic effects. RNA sequencing analysis revealed differential expression of various cellular factors, including RNA processing factors. Further investigation identified cell-type and time-dependent upregulation nonsense-mediated RNA decay (NMD), RNA degradation factors and nuclear pore complex (NPC) transcripts. Protein analysis showed that ZIKV, unlike DENV, degrades NMD factors in host cells, which along with mis-regulation of RNA degradation factors resulted in accumulation in host intronic transcripts as revealed by RNA-seq data. We also found that active nuclear transport is required for ZIKV replication, suggesting that therapeutic targeting of the NPC could potentially be effective in controlling ZIKV infection. Furthermore, from our findings we hypothesize that, ZIKV, but not DENV, drives early host cell cytopathy through targeted protein degradation. Current studies are underway to develop novel strategies to detect ZIKV, DENV and other flaviviruses in biologics based on transcriptomics and proteomics.TeaserExploring the molecular basis of flavivirus virulence in host cells.

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RNA virus infections and their effect on host alternative splicing

Cited by 5 publications

References 46 publications

Virus usurps alternative splicing to clear the decks for infection

Virus usurps alternative splicing to clear the decks for infection

Serine-arginine protein kinases and their targets in viral infection and their inhibition

Zika and Dengue Viruses Differentially Modulate Host mRNA Processing Factors Defining Its Virulence

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