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N6-Methyladenosine RNA Modification in Host Cells Regulates Peste des Petits Ruminants Virus Replication

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Title N6-Methyladenosine RNA Modification in Host Cells Regulates Peste des Petits Ruminants Virus Replication
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Creator Owais Khan
Gunturu Narasimha Tanuj
Divyaprakash R Choravada
Kaushal Kishore Rajak
S Chandra Sekar
Madhu Cholenahalli Lingaraju
Sujoy K Dhara
Praveen K Gupta
Bishnu Prasad Mishra
Triveni Dutt
Ravi Kumar Gandham
Basavaraj Sajjanar
 
Subject N6-methyladenosine (m6A); RNA modifications; small ruminant morbillivirus; virus replication; virus-host interactions
 
Description Not Available
N6-methyladenosine (m6A) modification is a major RNA epigenetic regulatory mechanism. The dynamics of m6A levels in viral genomic RNA and their mRNAs have been shown to have either pro- or antiviral functions, and therefore, m6A modifications influence virus-host interactions. Currently, no reports are available on the effect of m6A modifications in the genome of Peste des petits ruminants virus (PPRV). In the present study, we took PPRV as a model for nonsegmented negative-sense single-stranded RNA viruses and elucidate the role of m6A modification on viral replication. We detected m6A-modified sites in the mRNA of the virus and host cells, as well as the PPRV RNA genome. Further, it was found that the level of m6A modification in host cells alters the viral gene expression. Knockdown of the METTL3 and FTO genes (encoding the m6A RNA modification writer and eraser proteins, respectively) results in alterations of the levels of m6A RNA modifications in the host cells. Experiments using these genetically modified clones of host cells infected with PPRV revealed that both higher and lower m6A RNA modification in the host cells negatively affect PPRV replication. We found that m6A-modified viral transcripts had better stability and translation efficiency compared to the unmodified mRNA. Altogether, from these data, we conclude that the m6A modification of RNA regulates PPRV replication. These findings contribute toward a way forward for developing novel antiviral strategies against PPRV by modulating the dynamics of host m6A RNA modification
DBT/Wellcome Trust India Alliance (grant no. IA/E/17/1/503689 awarded to B.S.)
 
Date 2023-05-15T03:38:53Z
2023-05-15T03:38:53Z
2023-02
 
Type Research Paper
 
Identifier Khan O, Tanuj GN, Choravada DR, Rajak KK, Chandra Sekar S, Lingaraju MC, Dhara SK, Gupta PK, Mishra BP, Dutt T, Gandham RK, Sajjanar B. N6-Methyladenosine RNA Modification in Host Cells Regulates Peste des Petits Ruminants Virus Replication. Microbiol Spectr. 2023 Feb 14:e0266622. doi: 10.1128/spectrum.02666-22
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http://krishi.icar.gov.in/jspui/handle/123456789/77259
 
Language English
 
Relation Not Available;
 
Publisher American Society for Microbiology