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J Virol. 2012 Nov 14. [Epub ahead of print]
Myxovirus resistance gene A (MxA) expression suppresses Influenza A virus replication in Interferon-α stimulated primate cells.
Matzinger SR, Carroll TD, C Dutra J, Ma ZM, Miller CJ.
Source
Center for Comparative Medicine.
Abstract
Interferon-α production is triggered when influenza virus RNA is detected by appropriate pattern recognition receptors in the host cell. Interferon-α induces the expression of more than 300 interferon-stimulated genes (ISGs) and this blunts influenza virus replication. The human ISG, MxA can inhibit Influenza A virus replication in mouse cells by interfering with a step in the virus replication cycle after primary transcription of the negative strand RNA genome to mRNA (27). To determine the role of MxA in blocking human Influenza A virus replication in primate cells, we manipulated MxA expression in rhesus kidney epithelial cells (LLC-MK(2)) and human lung carcinoma cells (A549). We found that IFNα treatment prior to influenza virus infection suppressed virus replication and induced the expression of many ISGs, including MxA. However, IFNα mediated suppression of virus replication was abolished by siRNA knockdown of MxA expression in IFN-treated cells. In addition, influenza virus replication was suppressed in Vero cells stably transfected with MxA. A strand-specific RT-PCR assay showed that positive-strand influenza mRNA and negative-strand genomic RNA (gRNA) accumulated to high levels at 8 hrs after infection in control Vero cells containing the empty vector. However in Vero cells stably transfected with MxA positive-strand influenza mRNA, complimentary positive-strand influenza genome RNA (cRNA), and influenza gRNA were drastically suppressed. Thus, in primate cells, MxA inhibits human seasonal influenza virus replication at a step prior to primary transcription of gRNA into mRNA. Taken together, these results demonstrate that MxA mediates control of Influenza virus replication in primate cells treated with IFNα.
PMID:
23152507
[PubMed - as supplied by publisher]
Myxovirus resistance gene A (MxA) expression suppresses Influenza A virus replication in Interferon-α stimulated primate cells.
Matzinger SR, Carroll TD, C Dutra J, Ma ZM, Miller CJ.
Source
Center for Comparative Medicine.
Abstract
Interferon-α production is triggered when influenza virus RNA is detected by appropriate pattern recognition receptors in the host cell. Interferon-α induces the expression of more than 300 interferon-stimulated genes (ISGs) and this blunts influenza virus replication. The human ISG, MxA can inhibit Influenza A virus replication in mouse cells by interfering with a step in the virus replication cycle after primary transcription of the negative strand RNA genome to mRNA (27). To determine the role of MxA in blocking human Influenza A virus replication in primate cells, we manipulated MxA expression in rhesus kidney epithelial cells (LLC-MK(2)) and human lung carcinoma cells (A549). We found that IFNα treatment prior to influenza virus infection suppressed virus replication and induced the expression of many ISGs, including MxA. However, IFNα mediated suppression of virus replication was abolished by siRNA knockdown of MxA expression in IFN-treated cells. In addition, influenza virus replication was suppressed in Vero cells stably transfected with MxA. A strand-specific RT-PCR assay showed that positive-strand influenza mRNA and negative-strand genomic RNA (gRNA) accumulated to high levels at 8 hrs after infection in control Vero cells containing the empty vector. However in Vero cells stably transfected with MxA positive-strand influenza mRNA, complimentary positive-strand influenza genome RNA (cRNA), and influenza gRNA were drastically suppressed. Thus, in primate cells, MxA inhibits human seasonal influenza virus replication at a step prior to primary transcription of gRNA into mRNA. Taken together, these results demonstrate that MxA mediates control of Influenza virus replication in primate cells treated with IFNα.
PMID:
23152507
[PubMed - as supplied by publisher]
