+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Flavivirus RNA methylation

Flavivirus RNA methylation

Journal of General Virology 95(Pt 4): 763-778

The 5' end of eukaryotic mRNA contains the type-1 (m7GpppNm) or type-2 (m7GpppNmNm) cap structure. Many viruses have evolved various mechanisms to develop their own capping enzymes (e.g. flavivirus and coronavirus) or to 'steal' caps from host mRNAs (e.g. influenza virus). Other viruses have developed 'cap-mimicking' mechanisms by attaching a peptide to the 5' end of viral RNA (e.g. picornavirus and calicivirus) or by having a complex 5' RNA structure (internal ribosome entry site) for translation initiation (e.g. picornavirus, pestivirus and hepacivirus). Here we review the diverse viral RNA capping mechanisms. Using flavivirus as a model, we summarize how a single methyltransferase catalyses two distinct N-7 and 2'-O methylations of viral RNA cap in a sequential manner. For antiviral development, a structural feature unique to the flavivirus methyltransferase was successfully used to design selective inhibitors that block viral methyltransferase without affecting host methyltransferases. Functionally, capping is essential for prevention of triphosphate-triggered innate immune activation; N-7 methylation is critical for enhancement of viral translation; and 2'-O methylation is important for subversion of innate immune response during viral infection. Flaviviruses defective in 2'-O methyltransferase are replicative, but their viral RNAs lack 2'-O methylation and are recognized and eliminated by the host immune response. Such mutant viruses could be rationally designed as live attenuated vaccines. This concept has recently been proved with Japanese encephalitis virus and dengue virus. The findings obtained with flavivirus should be applicable to other RNA viruses.

Please choose payment method:

(PDF emailed within 0-6 h: $19.90)

Accession: 053258709

Download citation: RISBibTeXText

PMID: 24486628

DOI: 10.1099/vir.0.062208-0

Related references

Causes and Consequences of Flavivirus RNA Methylation. Frontiers in Microbiology 8: 2374, 2017

2'-O methylation of internal adenosine by flavivirus NS5 methyltransferase. Plos Pathogens 8(4): E1002642, 2012

Distinct RNA elements confer specificity to flavivirus RNA cap methylation events. Journal of Virology 81(9): 4412-4421, 2007

Rational design of a flavivirus vaccine by abolishing viral RNA 2'-O methylation. Journal of Virology 87(10): 5812-5819, 2013

Complete genome sequence of Menghai flavivirus, a novel insect-specific flavivirus from China. Archives of Virology 162(5): 1435-1439, 2017

Complete genome sequence of Xishuangbanna flavivirus, a novel mosquito-specific flavivirus from China. Archives of Virology 161(6): 1723-1727, 2016

Detection of a new insect flavivirus and isolation of Aedes flavivirus in Northern Italy. Parasites and Vectors 5: 223, 2012

A new flavivirus and a new vector: characterization of a novel flavivirus isolated from uranotaenia mosquitoes from a tropical rain forest. Journal of Virology 83(9): 4462-4468, 2009

Co-circulation of Aedes flavivirus, Culex flavivirus, and Quang Binh virus in Shanghai, China. Infectious Diseases of Poverty 7(1): 75, 2018

Recombinant vaccinia viruses expressing the flavivirus prm and e genes induce the synthesis of flavivirus like particles. Journal of Cellular Biochemistry Suppl. (16 Part C): 144, 1992

A novel recombinant adenovirus vector expressing a flavivirus non-structural protein protects against lethal flavivirus challenge. Clinical Science 85(2): 117-122, 1993

Isolation of a novel species of flavivirus and a new strain of Culex flavivirus (Flaviviridae) from a natural mosquito population in Uganda. Journal of General Virology 90(Pt 11): 2669-2678, 2009

A glance at subgenomic flavivirus RNAs and microRNAs in flavivirus infections. Virology Journal 13: 84, 2016

Detection of Culex flavivirus and Aedes flavivirus nucleotide sequences in mosquitoes from parks in the city of São Paulo, Brazil. Acta Tropica 157: 73-83, 2016

West Nile virus, Anopheles flavivirus, a novel flavivirus as well as Merida-like rhabdovirus Turkey in field-collected mosquitoes from Thrace and Anatolia. Infection Genetics and Evolution 57: 36-45, 2018