Cellular MicroRNAs Inhibit Replication of the H1N1 Influenza A Virus in Infected Cells

[tetano]

J Virol. 2010 Jun 16. [Epub ahead of print]
Cellular MicroRNAs Inhibit Replication of the H1N1 Influenza A Virus in Infected Cells.

Song L, Liu H, Gao S, Jiang W, Huang W.

CAS Key laboratory of Pathogen and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Chaoyang District, Beijing 100101, China; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060.
Abstract

MicroRNAs (miRNAs) are a class of non-coding RNAs of lengths ranging from 18-23 nucleotides that play critical roles in a wide variety of biological processes. There is a growing amount of evidence that miRNAs play critical roles in intricate host-pathogen interaction networks, but the involvement of miRNAs during influenza viral infection is unknown. To determine whether the cellular miRNAs play an important role in H1N1 influenza A viral infections, 3UTR reporter analysis was used to identify putative miRNA targets in the influenza virus genome, and virus proliferation analysis was used to detect the effect of the screened miRNAs on the replication of H1N1 influenza A virus(A/WSN/33)in MDCK cells. The results showed that miR-323, miR-491, and miR-654 inhibit replication of the H1N1 influenza A virus through binding to pb1. Moreover mutational analysis of the predicted miRNA binding sites showed that the three miRNAs bind to the same conserved region of the pb1 gene. Intriguingly, despite the fact that the miRNAs and pb1 mRNA binding sequences are not a perfect match, the miRNAs downregulate pb1 expression through mRNA degradation instead of translation repression. This is the first demonstration that cellular miRNAs regulate influenza viral replication by degradation of the viral gene. Our findings support the notion that any miRNA has antiviral potential, independent of its cellular function, and that the cellular miRNAs play an important role in the host, defending against virus infection.

PMID: 20554777 [PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/20554777

 

[mixin]

Re: Cellular MicroRNAs Inhibit Replication of the H1N1 Influenza A Virus in Infected Cells

It's interesting to watch the interaction between the host and the invader.

Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands

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We show that the mutant virus is attenuated specifically in the salivary glands of infected mice, an organ essential for long-term persistence of the virus and host-to-host spread. Interestingly, this attenuation revealed a striking dependence on genetic background of the mice under study. Only combined depletion of natural killer and T cells abolished the phenotype. These results indicate that, by regulating the immune system, viral miRNAs may play an important role in an efficient persistent infection.

Notably, control of MCMV in salivary glands is completely different than in any other tissue. The virus counteracts host defenses in this sentinel organ by means that are still not fully understood. Virus persistence in salivary gland tissues appears mainly to reflect the situation in acinar glandular epithelial cells. In these cells, MCMV replicates to high titers with a distinct morphogenesis and without causing gross tissue damage [20]. Infectious particles are stored and secreted from large cytoplasmic vacuoles, orientated towards excretion ducts, filled with high numbers (~1,000) of virions [21]. Interestingly, for unknown reasons, virus isolated from salivary glands of naive mice at 14 dpi is also several fold more virulent than virus coming from any other organ or from cell culture. This gain in virulence is lost after a single round of replication in tissue culture

In salivary glands MCMV infection is almost completely resistant to immunological control by CD8+ T cells. Only the concerted action of CD4+ T cells and cells with a natural killer (NK) cell-like phenotype finally results in termination of productive infection after many weeks or even months of infection [8], [9]. As such, CD4+ T cell deficient mice establish persistent infection for many months, which is restricted to salivary gland

D?lken L, Krmpotic A, Kothe S, Tuddenham L, Tanguy M, et al. 2010 Cytomegalovirus microRNAs Facilitate Persistent Virus Infection in Salivary Glands. PLoS Pathog 6(10): e1001150. doi:10.1371/journal.ppat.1001150
Full .pdf http://www.plospathogens.org/articl.../NewArticles+(Ambra+-+Pathogens+New+Articles)