Abstract
BackgroundIn our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison), we found that these differences were related to amino acid variations in the NS1 protein. In this study, we extend our previous work to further investigate the effect of the NS1 from different gene pools on type I IFN promoter activity, the production of IFN-β, as well as the expression of the IFN-β mRNA in response to poly I:C.ResultsUsing a model system, we first demonstrated that NS1 from A/mink/Sweden/84 (H10N4) (allele A) could suppress an interferon-stimulated response element (ISRE) reporter system to about 85%. The other NS1 (allele B), from A/chicken/Germany/N/49 (H10N7), was also able to suppress the reporter system, but only to about 20%. The differences in the abilities of the two NS1s from different alleles to suppress the ISRE reporter system were clearly reflected by the protein and mRNA expressions of IFN-β as shown by ELISA and RT-PCR assays.ConclusionsThese studies reveal that different non-structural protein 1 (NS1) of influenza viruses, one from allele A and another from allele B, show different abilities to suppress the type I interferon β expression. It has been hypothesised that some of the differences in the different abilities of the alleles to suppress ISRE were because of the interactions and inhibitions at later stages from the IFN receptor, such as the JAK/STAT pathway. This might reflect the additional effects of the immune evasion potential of different NS1s.
Highlights
In our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison), we found that these differences were related to amino acid variations in the non-structural protein 1 (NS1) protein
Activation of IFN-b promoter First, we studied the ability of NS1 from “mink/84” and “chicken/49” to inhibit the induction of transcription of the IFN-b gene, using the model system interferon-stimulated response element (ISRE)-Luciferase and Poly I:C stimulation
The NS1 proteins from both constructs were expressed in high quantity and the level of allele A NS1 was comparable to NS1 protein of allele B (Figure 1B)
Summary
In our previous study concerning the genetic relationship among H10 avian influenza viruses with different pathogenicity in mink (Mustela vison), we found that these differences were related to amino acid variations in the NS1 protein. Viral infections trigger the production of type I IFNs (IFN-a/b) [1,2], which leads to the activation of several hundred IFN-stimulated genes (ISGs). The main viral sensors in most mammalian nucleated cells are RNA helicases, retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA-5), which recognises viral single-stranded RNA (ssRNA) and double-stranded RNA (dsRNA) [1,5,6,7,8,9]. The binding of virus-derived nucleic acids to RIG-I, MDA-5 or TLR3 results in a coordinated activation of the transcription factors nuclear factor kappa B (NF-B) and interferon regulatory factor 3 (IRF-3), leading to IFN-b production in mammals [6,7,10]
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