Multiple anti-interferon actions of the influenza A virus NS1 protein.

نویسندگان

  • Georg Kochs
  • Adolfo García-Sastre
  • Luis Martínez-Sobrido
چکیده

The replication and pathogenicity of influenza A virus (FLUAV) are controlled in part by the alpha/beta interferon (IFN-alpha/beta) system. This virus-host interplay is dependent on the production of IFN-alpha/beta and on the capacity of the viral nonstructural protein NS1 to counteract the IFN system. Two different mechanisms have been described for NS1, namely, blocking the activation of IFN regulatory factor 3 (IRF3) and blocking posttranscriptional processing of cellular mRNAs. Here we directly compare the abilities of NS1 gene products from three different human FLUAV (H1N1) strains to counteract the antiviral host response. We found that A/PR/8/34 NS1 has a strong capacity to inhibit IRF3 and activation of the IFN-beta promoter but is unable to suppress expression of other cellular genes. In contrast, the NS1 proteins of A/Tx/36/91 and of A/BM/1/18, the virus that caused the Spanish influenza pandemic, caused suppression of additional cellular gene expression. Thus, these NS1 proteins prevented the establishment of an IFN-induced antiviral state, allowing virus replication even in the presence of IFN. Interestingly, the block in gene expression was dependent on a newly described NS1 domain that is important for interaction with the cleavage and polyadenylation specificity factor (CPSF) component of the cellular pre-mRNA processing machinery but is not functional in A/PR/8/34 NS1. We identified the Phe-103 and Met-106 residues in NS1 as being critical for CPSF binding, together with the previously described C-terminal binding domain. Our results demonstrate the capacity of FLUAV NS1 to suppress the antiviral host defense at multiple levels and the existence of strain-specific differences that may modulate virus pathogenicity.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Applying conserved peptides of NS1 Protein of avian influenza virus to differentiate infected from vaccinated chickens

Avian influenza (AI) is a highly contagious disease in poultry and outbreaks can have dramatic economic and health implications. For effective disease surveillance, rapid and sensitive assays are needed to detect antibodies against AI virus (AIV) proteins. In order to support eradication efforts of avian influenza (AI) infections in poultry, the implementation of “DIVA” vaccination strategies, ...

متن کامل

Cloning and Expression of Influenza H1N1 NS1 Protein in Escherichia Coli BL21

Background:Influenza virus is globally pathogenic and it is usually associated with zoonotic respiratory diseases. This virus has caused a number of pandemics with a high mortality rate. The non-structural (NS1) protein of influenza A viruses is a non-essential virulence factor that has multiple accessory functions during viral infection. This protein is highly conservative. It has been shown t...

متن کامل

Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs.

It has been shown previously that the nonstructural protein NS1 of influenza virus is an alpha/beta interferon (IFN-alpha/beta) antagonist, both in vitro and in experimental animal model systems. However, evidence of this function in a natural host has not yet been obtained. Here we investigated the role of the NS1 protein in the virulence of a swine influenza virus (SIV) isolate in pigs by usi...

متن کامل

Novel influenza virus NS1 antagonists block replication and restore innate immune function.

The innate immune system guards against virus infection through a variety of mechanisms including mobilization of the host interferon system, which attacks viral products mainly at a posttranscriptional level. The influenza virus NS1 protein is a multifunctional facilitator of virus replication, one of whose actions is to antagonize the interferon response. Since NS1 is required for efficient v...

متن کامل

Truncation of the NS1 protein converts a low pathogenic avian influenza virus into a strong interferon inducer in duck cells.

The NS1 protein of influenza A viruses is known as a nonessential virulence factor inhibiting type I interferon (IFN) production in mammals and in chicken cells. Whether NS1 inhibits the induction of type I IFNs in duck cells is currently unknown. In order to investigate this issue, we used reverse genetics to generate a virus expressing a truncated NS1 protein. Using the low pathogenic avian i...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of virology

دوره 81 13  شماره 

صفحات  -

تاریخ انتشار 2007