Unique signatures Of long noncoding RNA expression in response to virus infection And altered innate immune signaling
MetadataShow full item record
AbstractStudies of the host response to virus infection typically focus on protein-coding genes. However, non-protein-coding RNAs (ncRNAs) are transcribed in mammalian cells, and the roles of many of these ncRNAs remain enigmas. Using nextgeneration sequencing, we performed a whole-transcriptome analysis of the host response to severe acute respiratory syndrome coronavirus (SARS-CoV) infection across four founder mouse strains of the Collaborative Cross. We observed differential expression of approximately 500 annotated, long ncRNAs and 1,000 nonannotated genomic regions during infection. Moreover, studies of a subset of these ncRNAs and genomic regions showed the following. (i) Most were similarly regulated in response to influenza virus infection. (ii) They had distinctive kinetic expression profiles in type I interferon receptor and STAT1 knockout mice during SARS-CoV infection, including unique signatures of ncRNA expression associated with lethal infection. (iii) Over 40% were similarly regulated in vitro in response to both influenza virus infection and interferon treatment. These findings represent the first discovery of the widespread differential expression of long ncRNAs in response to virus infection and suggest that ncRNAs are involved in regulating the host response, including innate immunity. At the same time, virus infection models provide a unique platform for studying the biology and regulation of ncRNAs. IMPORTANCE Most studies examining the host transcriptional response to infection focus only on protein-coding genes. However, there is growing evidence that thousands of non-protein-coding RNAs (ncRNAs) are transcribed from mammalian genomes. While most attention to the involvement of ncRNAs in virus-host interactions has been on small ncRNAs such as microRNAs, it is becoming apparent that many long ncRNAs (>200 nucleotides [nt]) are also biologically important. These long ncRNAs have been found to have widespread functionality, including chromatin modification and transcriptional regulation and serving as the precursors of small RNAs. With the advent of next-generation sequencing technologies, whole-transcriptome analysis of the host response, including long ncRNAs, is now possible. Using this approach, we demonstrated that virus infection alters the expression of numerous long ncRNAs, suggesting that these RNAs may be a new class of regulatory molecules that play a role in determining the outcome of infection. Copyright 2010 Peng et al.
severe acute respiratory syndrome coronavirus
RNA, Long Noncoding
Identifier to cite or link to this itemhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-79952137666&doi=10.1128%2fmBio.00206-10&partnerID=40&md5=972112920115df607c966809ede56ba5; http://hdl.handle.net/10713/12429
- Integrative deep sequencing of the mouse lung transcriptome reveals differential expression of diverse classes of small RNAs in response to respiratory virus infection.
- Authors: Peng X, Gralinski L, Ferris MT, Frieman MB, Thomas MJ, Proll S, Korth MJ, Tisoncik JR, Heise M, Luo S, Schroth GP, Tumpey TM, Li C, Kawaoka Y, Baric RS, Katze MG
- Issue date: 2011
- SARS-CoV pathogenesis is regulated by a STAT1 dependent but a type I, II and III interferon receptor independent mechanism.
- Authors: Frieman MB, Chen J, Morrison TE, Whitmore A, Funkhouser W, Ward JM, Lamirande EW, Roberts A, Heise M, Subbarao K, Baric RS
- Issue date: 2010 Apr 8
- Complement Activation Contributes to Severe Acute Respiratory Syndrome Coronavirus Pathogenesis.
- Authors: Gralinski LE, Sheahan TP, Morrison TE, Menachery VD, Jensen K, Leist SR, Whitmore A, Heise MT, Baric RS
- Issue date: 2018 Oct 9
- Early upregulation of acute respiratory distress syndrome-associated cytokines promotes lethal disease in an aged-mouse model of severe acute respiratory syndrome coronavirus infection.
- Authors: Rockx B, Baas T, Zornetzer GA, Haagmans B, Sheahan T, Frieman M, Dyer MD, Teal TH, Proll S, van den Brand J, Baric R, Katze MG
- Issue date: 2009 Jul
- Toll-Like Receptor 3 Signaling via TRIF Contributes to a Protective Innate Immune Response to Severe Acute Respiratory Syndrome Coronavirus Infection.
- Authors: Totura AL, Whitmore A, Agnihothram S, Schäfer A, Katze MG, Heise MT, Baric RS
- Issue date: 2015 May 26