Unique signatures of long noncoding RNA expression in response to virus infection and altered innate immune signaling.
Studies 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 next-generation 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.
Peng
Xinxia
X
Department of Microbiology, School of Medicine, University of Washington, Seattle, Washington, USA.
Gralinski
Lisa
L
Armour
Christopher D
CD
Ferris
Martin T
MT
Thomas
Matthew J
MJ
Proll
Sean
S
Bradel-Tretheway
Birgit G
BG
Korth
Marcus J
MJ
Castle
John C
JC
Biery
Matthew C
MC
Bouzek
Heather K
HK
Haynor
David R
DR
Frieman
Matthew B
MB
Heise
Mark
M
Raymond
Christopher K
CK
Baric
Ralph S
RS
Katze
Michael G
MG
D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D051379:Mice; D022661:RNA, Untranslated / Q000096:biosynthesis*; D045473:Severe acute respiratory syndrome-related coronavirus / Q000276:immunology* / Q000472:pathogenicity; D045169:Severe Acute Respiratory Syndrome / Q000276:immunology* / Q000473:pathology / Q000821:virology; D015398:Signal Transduction; D014158:Transcription, Genetic
D022661:RNA, Untranslated