NS1 Influenza Protein
Encyclopedia
The NS1 Influenza Protein is created by the internal protein encoding, linear negative-sense, single stranded RNA
, NS gene segment; which found in Influenzavirus A
, Influenzavirus B
and Influenzavirus C
; and which also codes for the nuclear export protein or NEP, formerly referred to as the NS2 protein, which mediates the export of vRNP
s.
The influenza
protein NS1 is a 26,000 Dalton
protein. Human messenger RNA
carries a poly(A) tail at the 3' end. NS1 forms a dimer that inhibits the export of poly(A) containing mRNA molecules from the nucleus. This gives preference to viral RNA. NS1 might also inhibit splicing of pre-mRNA by binding to a stem-bulge region in U6 small nuclear RNA (snRNA). In addition, NS1 is probably able to suppress the interferon
response in the virus-infected cell leading to unimpaired virus production.
NS1 also binds dsRNA. Binding assays with NS1 protein mutants established that the RNA-binding domain of the NS1 protein is required for binding to dsRNA as well as for binding to polyA and U6 snRNA. In addition, dsRNA competed with U6 snRNA for binding to the NS1 protein, a result consistent with both RNAs sharing the same binding site on the protein. As a consequence of its binding to dsRNA, the NS1 protein blocks the activation of the dsRNA-activated protein kinase
(PKR
) in vitro. This kinase phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of initiation of translation
. In the absence of NS1, this pathway is inhibited during anti-viral response to halt all protein translation - thus stopping the synthesis of viral proteins; however, the influenza virus' NS1 protein is an agent that circumvents host defenses to allows viral gene transcription to occur.
The NS1 protein of the highly pathogenic avian H5N1
viruses circulating in poultry and waterfowl in Southeast Asia is currently believed to be responsible for the enhanced virulence of the strain. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, researchers were able to annul the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus.
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....
, NS gene segment; which found in Influenzavirus A
Influenzavirus A
Influenza A virus causes influenza in birds and some mammals and is the only species of Influenzavirus A. Influenzavirus A is a genus of the Orthomyxoviridae family of viruses. Strains of all subtypes of influenza A virus have been isolated from wild birds, although disease is uncommon...
, Influenzavirus B
Influenzavirus B
Influenzavirus B is a genus in the virus family Orthomyxoviridae. The only species in this genus is called "Influenza B virus".Influenza B viruses are only known to infect humans and seals, giving them influenza...
and Influenzavirus C
Influenzavirus C
Influenzavirus C is a genus in the virus family Orthomyxoviridae, which includes those viruses which cause influenza. The only species in this genus is called "Influenza C virus".Influenza C viruses are known to infect humans and pigs, giving them influenza...
; and which also codes for the nuclear export protein or NEP, formerly referred to as the NS2 protein, which mediates the export of vRNP
Ribonucleoprotein
Ribonucleoprotein is a nucleoprotein that contains RNA, i.e. it is an association that combines ribonucleic acid and protein together. A few known examples include the ribosome, the enzyme telomerase, vault ribonucleoproteins, and small nuclear RNPs , which are implicated in pre-mRNA splicing and...
s.
The influenza
Influenza
Influenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
protein NS1 is a 26,000 Dalton
Atomic mass unit
The unified atomic mass unit or dalton is a unit that is used for indicating mass on an atomic or molecular scale. It is defined as one twelfth of the rest mass of an unbound neutral atom of carbon-12 in its nuclear and electronic ground state, and has a value of...
protein. Human messenger RNA
Messenger RNA
Messenger RNA is a molecule of RNA encoding a chemical "blueprint" for a protein product. mRNA is transcribed from a DNA template, and carries coding information to the sites of protein synthesis: the ribosomes. Here, the nucleic acid polymer is translated into a polymer of amino acids: a protein...
carries a poly(A) tail at the 3' end. NS1 forms a dimer that inhibits the export of poly(A) containing mRNA molecules from the nucleus. This gives preference to viral RNA. NS1 might also inhibit splicing of pre-mRNA by binding to a stem-bulge region in U6 small nuclear RNA (snRNA). In addition, NS1 is probably able to suppress the interferon
Interferon
Interferons are proteins made and released by host cells in response to the presence of pathogens—such as viruses, bacteria, or parasites—or tumor cells. They allow communication between cells to trigger the protective defenses of the immune system that eradicate pathogens or tumors.IFNs belong to...
response in the virus-infected cell leading to unimpaired virus production.
NS1 also binds dsRNA. Binding assays with NS1 protein mutants established that the RNA-binding domain of the NS1 protein is required for binding to dsRNA as well as for binding to polyA and U6 snRNA. In addition, dsRNA competed with U6 snRNA for binding to the NS1 protein, a result consistent with both RNAs sharing the same binding site on the protein. As a consequence of its binding to dsRNA, the NS1 protein blocks the activation of the dsRNA-activated protein kinase
Kinase
In chemistry and biochemistry, a kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. Kinases are part of the larger family of phosphotransferases...
(PKR
Protein kinase R
Protein kinase RNA-activated also known as protein kinase R , interferon-induced, double-stranded RNA-activated protein kinase, or eukaryotic translation initiation factor 2-alpha kinase 2 is an enzyme that in humans is encoded by the EIF2AK2 gene.PKR protects against viral...
) in vitro. This kinase phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (elF-2 alpha), leading to a decrease in the rate of initiation of translation
Translation (genetics)
In molecular biology and genetics, translation is the third stage of protein biosynthesis . In translation, messenger RNA produced by transcription is decoded by the ribosome to produce a specific amino acid chain, or polypeptide, that will later fold into an active protein...
. In the absence of NS1, this pathway is inhibited during anti-viral response to halt all protein translation - thus stopping the synthesis of viral proteins; however, the influenza virus' NS1 protein is an agent that circumvents host defenses to allows viral gene transcription to occur.
The NS1 protein of the highly pathogenic avian H5N1
H5N1
Influenza A virus subtype H5N1, also known as "bird flu", A or simply H5N1, is a subtype of the influenza A virus which can cause illness in humans and many other animal species...
viruses circulating in poultry and waterfowl in Southeast Asia is currently believed to be responsible for the enhanced virulence of the strain. H5N1 NS1 is characterized by a single amino acid change at position 92. By changing the amino acid from glutamic acid to aspartic acid, researchers were able to annul the effect of the H5N1 NS1. This single amino acid change in the NS1 gene greatly increased the pathogenicity of the H5N1 influenza virus.
See also
- H5N1 genetic structureH5N1 genetic structureH5N1 genetic structure is the molecular structure of the H5N1 virus's RNA.H5N1 is an Influenza A virus subtype. Experts believe it might mutate into a form that transmits easily from person to person...
- InfluenzaInfluenzaInfluenza, commonly referred to as the flu, is an infectious disease caused by RNA viruses of the family Orthomyxoviridae , that affects birds and mammals...
- NCBI Flu Genome Database