Treatment of Sindbis Virus-Infected Neurons with Antibody to E2 Alters Synthesis of Complete and nsP1-Expressing Defective Viral RNAs

Yeh, Jane; Fan, Yunfan; Bartlett, Maggie; Zhang, Xiaoyan; Sadowski, Norah; Hauer, Debra; Timp, Winston; Griffin, Diane E.

doi:10.1128/mbio.02221-22

Cited by 1 publication

(1 citation statement)

References 62 publications

(103 reference statements)

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“…The infectivity of released virus particles generally improves as infection progresses, and this pattern was observed in our studies of viruses produced by C8-D1A cells. Because genomes must be capped to be infectious, it is possible that capping becomes more efficient later in infection with an accumulation of nsP1, and that overproduction of structural proteins results in virions being assembled with genomes that have not been capped or with defective viral genomes [101]. Alternatively, as identified for virions produced in response to increased structural protein synthesis associated with decreased hnRNPI binding to the 3 UTR of SINV sgRNA, glycosylation of the E1 and E2 glycoproteins may be defective [100].…”

Section: Discussionmentioning

confidence: 99%

Cell-Type-Dependent Role for nsP3 Macrodomain ADP-Ribose Binding and Hydrolase Activity during Chikungunya Virus Infection

Kim

Abraham

Pieterse

et al. 2022

Viruses

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Chikungunya virus (CHIKV) causes outbreaks of rash, arthritis, and fever associated with neurologic complications, where astrocytes are preferentially infected. A determinant of virulence is the macrodomain (MD) of nonstructural protein 3 (nsP3), which binds and removes ADP-ribose (ADPr) from ADP-ribosylated substrates and regulates stress-granule disruption. We compared the replication of CHIKV 181/25 (WT) and MD mutants with decreased ADPr binding and hydrolase (G32S) or increased ADPr binding and decreased hydrolase (Y114A) activities in C8-D1A astrocytic cells and NSC-34 neuronal cells. WT CHIKV replication was initiated more rapidly with earlier nsP synthesis in C8-D1A than in NSC-34 cells. G32S established infection, amplified replication complexes, and induced host-protein synthesis shut-off less efficiently than WT and produced less infectious virus, while Y114A replication was close to WT. However, G32S mutation effects on structural protein synthesis were cell-type-dependent. In NSC-34 cells, E2 synthesis was decreased compared to WT, while in C8-D1A cells synthesis was increased. Excess E2 produced by G32S-infected C8-D1A cells was assembled into virus particles that were less infectious than those from WT or Y114A-infected cells. Because nsP3 recruits ADP-ribosylated RNA-binding proteins in stress granules away from translation-initiation factors into nsP3 granules where the MD hydrolase can remove ADPr, we postulate that suboptimal translation-factor release decreased structural protein synthesis in NSC-34 cells while failure to de-ADP-ribosylate regulatory RNA-binding proteins increased synthesis in C8-D1A cells.

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Section: Discussionmentioning

confidence: 99%

Cell-Type-Dependent Role for nsP3 Macrodomain ADP-Ribose Binding and Hydrolase Activity during Chikungunya Virus Infection

Kim

Abraham

Pieterse

et al. 2022

Viruses

Self Cite

View full text Add to dashboard Cite

show abstract

Treatment of Sindbis Virus-Infected Neurons with Antibody to E2 Alters Synthesis of Complete and nsP1-Expressing Defective Viral RNAs

Abstract: Alphaviruses are important causes of viral encephalomyelitis without approved treatments or vaccines. Antibody to the Sindbis virus (SINV) E2 glycoprotein is required for immune-mediated noncytolytic virus clearance from neurons.

Cited by 1 publication

References 62 publications

Cell-Type-Dependent Role for nsP3 Macrodomain ADP-Ribose Binding and Hydrolase Activity during Chikungunya Virus Infection

Cell-Type-Dependent Role for nsP3 Macrodomain ADP-Ribose Binding and Hydrolase Activity during Chikungunya Virus Infection

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