TY - JOUR

T1 - Differences in the ability to suppress interferon β production between allele A and allele B NS1 proteins from H10 influenza A viruses

AU - Zohari, Siamak

AU - Munir, Muhammad

AU - Metreveli, Giorgi

AU - Belák, Sándor

AU - Berg, Mikael

PY - 2010/12/31

Y1 - 2010/12/31

N2 - BACKGROUND: 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. 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.RESULTS: Using 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.CONCLUSIONS: These 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.

AB - BACKGROUND: 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. 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.RESULTS: Using 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.CONCLUSIONS: These 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.

KW - Alleles

KW - Animals

KW - Cell Line, Tumor

KW - Gene Expression Regulation

KW - Humans

KW - Influenza A virus

KW - Interferon Inducers

KW - Interferon-beta

KW - Poly I-C

KW - Promoter Regions, Genetic

KW - Viral Nonstructural Proteins

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1186/1743-422X-7-376

DO - 10.1186/1743-422X-7-376

M3 - Journal article

C2 - 21194454

VL - 7

JO - Virology Journal

JF - Virology Journal

SN - 1743-422X

M1 - 376

ER -