Abstract
MicroRNAs have been implicated in the regulation of gene expression of various biological processes in a post-transcriptional manner under physiological and pathological conditions including host responses to viral infections. The 2009 pandemic H1N1 influenza virus is an emerging reassortant strain of swine, human and bird influenza virus that can cause mild to severe illness and even death. To further understand the molecular pathogenesis of the 2009 pandemic H1N1 influenza virus, we profiled cellular microRNAs of lungs from BALB/c mice infected with wild-type 2009 pandemic influenza virus A/Beijing/501/2009 (H1N1) (hereafter referred to as BJ501) and mouse-adapted influenza virus A/Puerto Rico/8/1934 (H1N1) (hereafter referred to as PR8) for comparison. Microarray analysis showed both the influenza virus BJ501 and PR8 infection induced strain- and temporal-specific microRNA expression patterns and that their infection caused a group of common and distinct differentially expressed microRNAs. Characteristically, more differentially expressed microRNAs were aroused on day 5 post infection than on day 2 and more up-regulated differentially expressed microRNAs were provoked than the down-regulated for both strains of influenza virus. Finally, 47 differentially expressed microRNAs were obtained for the infection of both strains of H1N1 influenza virus with 29 for influenza virus BJ501 and 43 for PR8. Among them, 15 microRNAs had no reported function, while 32 including miR-155 and miR-233 are known to play important roles in cancer, immunity and antiviral activity. Pathway enrichment analyses of the predicted targets revealed that the transforming growth factor-β (TGF-β) signaling pathway was the key cellular pathway associated with the differentially expressed miRNAs during influenza virus PR8 or BJ501 infection. To our knowledge, this is the first report of microRNA expression profiles of the 2009 pandemic H1N1 influenza virus in a mouse model, and our findings might offer novel therapy targets for influenza virus infection.
Highlights
Influenza A viruses infecting humans are responsible for a variety of illnesses ranging from mild infection to more severe pneumonia associated with acute respiratory distress syndrome
The virus strains used in this study included influenza virus A/Beijing/501/2009 (H1N1), an influenza virus isolated from a confirmed H1N1 influenza case in Beijing during 2009 [26,27], and A/Puerto Rico/8/34 (H1N1), a well characterized and mouse-adapted laboratory strain of influenza virus used as the genetic backbone for viruses from which inactivated influenza virus vaccines are generated
We found that 86.11% (31 of 36) of the relative real-time reverse transcription polymerase chain reaction (RT-PCR) results were consistent with those obtained in the microRNA microarray analysis in terms of direction of regulation at one or more time points except the results of miR-574-3p in BJ501-infected lung on 2 dpi, miR-1 in PR8-infected lung on 2 dpi, miR-1 in BJ501-infected lung on 5 dpi, miR-133a in PR8-infected lung on 2 dpi and miR-133b in PR8-infected lung on 2 dpi (Figure 5)
Summary
Influenza A viruses infecting humans are responsible for a variety of illnesses ranging from mild infection to more severe pneumonia associated with acute respiratory distress syndrome. Even in non-pandemic years, influenza A viruses infect 5–15% of the global population and result in > 500,000 deaths annually [1]. In 2009, a novel strain of H1N1 influenza virus emerged in California and rapidly spread throughout the world [2]. A recent study estimated that > 284,000 deaths occurred globally during the first 12 months of 2009 pandemic H1N1virus circulation [3]. Given the possibility of reassortment of the 2009 pandemic H1N1 influenza virus, highly pathogenic. H5N1 influenza viruses or co-circulating seasonal human H1N1 viruses, the threat posed by the 2009 pandemic H1N1 virus to humans remains significant [4,5]. Understanding the pathogenesis of influenza virus infection is essential to preventing and controlling future outbreaks
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
