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Abstract
Influenza virus, a highly infectious ssRNA virus, replicates in the nucleus of host cells. This unusual feature brings the possibility that the virus may hijack host small noncoding RNA metabolism. Influenza small viral RNA production has been examined in vitro but has not yet been studied in an in vivo setting. We assessed small RNA species from influenza virus during mouse infection by mining publicly available mouse small RNA transcriptome data. We uncovered 26 nt reads corresponding to svRNA, a small viral RNA previously detected in vitro that regulates the transition from transcription to replication during infection, and found a strong positive correlation between svRNA production and host susceptibility to influenza virus infection. We also detected significant overrepresentation of a non-coding 23 nt sequence that we speculate may behave like a miRNA and work with influenza protein NS1 to prevent the transcription and maturation of interferon-stimulated mRNAs.
Highlights
Influenza A virus is a highly infectious seasonal pathogen responsible for substantial global morbidity and mortality
Infection by multiple influenza A virus subtypes in cell lines derived from multiple mammalian species can produce small viral RNAs (svRNAs) [5]
Ours is the first report of the production of influenza virus svRNA in vivo
Summary
Influenza A virus is a highly infectious seasonal pathogen responsible for substantial global morbidity and mortality. Annual epidemics affect 5–10% of adults and 20–30% of children, and cause approximately half a million deaths worldwide [1]. The economic impact of this infectious disease is staggering; the total annual economic burden of influenza epidemics in the United States alone is estimated to be over $87 billion considering both direct medical costs and lost earnings [2]. The influenza virus genome is organized into eight single-stranded RNA (ssRNA) segments of negative polarity that code for 11 genes [3,4] (Table 1). After adsorption and entry into the nucleus of the host cell, the genomic viral ssRNA (vRNA) is used as a template to synthesize ssRNA of positive polarity: either messenger RNAs (mRNA) for translation, or full length complementary copies (cRNA) used as intermediates to produce more vRNA (3). The virus alternates between making mRNA and cRNA, generating either viral proteins or additional progeny virions
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