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Epitranscriptomic Regulation of Alphavirus Replication and Transmission

甲病毒复制和传播的表观转录调控

基本信息

批准号：
10040109
负责人：
RICHARD W HARDY
金额：
$ 19.11万
依托单位：
TRUSTEES OF INDIANA UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-06-03 至 2022-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10040109
关键词：
Address Africa Alphavirus Americas Antiviral Agents Arthritis Biological Caribbean region Cell physiology Cells Cessation of life Chikungunya virus Clinical Complex Culicidae Cytosine Data Development Disease Outbreaks Eastern Equine Encephalitis Virus Encephalitis Epidemic Family Flavivirus Genome Goals HIV Health Height Hepatitis C virus Human Hypermethylation Immunoprecipitation Indian Ocean Infection Insecta Intervention Investigation Link Methylation Methyltransferase Modification Molecular Mutate Mutation Nucleotides Outcome Pattern Periodicity Play Population Positioning Attribute Public Health Publishing RNA RNA Viruses Regulation Reporting Research Role Security Severity of illness Sindbis Virus Southern Asia Stress Techniques Technology Testing Therapeutic Transfer RNA Translations United States Vaccines Viral Viral Genome Virus Virus Diseases Virus Replication Work Zika Virus base bisulfite sequencing epitranscriptomics genomic RNA global health member nanopore novel overexpression particle pathogen socioeconomics transcriptome sequencing transmission process viral RNA viral genomics viral transmission

项目摘要

Summary Alphaviruses represent a continuingly emerging challenge to global public health. This is exemplified by the spread of chikungunya virus from Africa through southern Asia and into the Americas. Additionally, this past summer has seen an increase in the number of eastern equine encephalitis virus infections and deaths in the United States. A deeper understanding of the determinants of efficient transmission and replication is needed to identify targets for transmission interventions. In recent years it has become apparent that modification of viral RNA impacts it’s function, and the outcome of infection. The proposed research extends on published and preliminary observations that implicate a particular epitranscriptomic modification of the viral genomic RNA in the determination of transmission efficiency. This proposal investigates the novel hypothesis that host species specific modification of the packaged viral genomic RNA impacts the ability of the particle to establish infection in the next host cell, a prospect of significant consequence for alphaviruses that obligatorily cycle between mosquito and vertebrate hosts. To examine this the proposed research will: (i) employ multiple sequencing technologies to determine the methylation state of cytosine residues in the genome of particles produced in vertebrate and mosquito cells; (ii) examine the biological consequence of disrupting the methylation of the viral genome through altering the methyltransferase and/or mutating residues found to be frequently modified. The results of this work will elucidate the pro- and anti-viral effects of cytosine methylation of viral RNA, and lay the ground work for further investigation of host-specific epitranscriptomic modifications and their role in virus replication and transmission.

总结