NSP1 (rotavirus)
Encyclopedia
NSP1, the product of rotavirus
Rotavirus
Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five,...

 gene 5, is an nonstructural
Nonstructural protein
In virology, a nonstructural protein is a protein encoded by a virus but it is not part of the viral particle....

 RNA-binding protein that contains a cysteine-rich region and is a component of early replication intermediates. RNA-folding
RNA structure
Biomolecular structure is the structure of biomolecules, mainly proteins and the nucleic acids DNA and RNA. The structure of these molecules is frequently decomposed into primary structure, secondary structure, tertiary structure, and quaternary structure. The scaffold for this structure is...

 predictions suggest that this region of the NSP1 mRNA
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...

 can interact with itself, producing a stem-loop structure similar to that found near the 5'-terminus of the NSP1 mRNA
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...

.

The carboxyl-half of the rotavirus
Rotavirus
Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five,...

 nonstructural protein NSP1 is not required for virus replication.

NSP1 could play a role in host range restriction.

The cysteine-rich region of NSP1 is not considered essential for genome segment reassortment with heterologous virus.

NSP1 interacts with IRF3
IRF3
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.- Function :IRF3 is a member of the interferon regulatory transcription factor family. IRF3 was originally discovered as a homolog of IRF1 and IRF2...

 in the infected cell. NSP1 is an antagonist of the IFN-signaling pathway.

Interferon regulatory factor 3 (IRF3
IRF3
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.- Function :IRF3 is a member of the interferon regulatory transcription factor family. IRF3 was originally discovered as a homolog of IRF1 and IRF2...

) is a key transcription factor involved in the induction of interferon (IFN) in response to viral infection. NSP1 binds to and targets IRF3 for proteasome
Proteasome
Proteasomes are very large protein complexes inside all eukaryotes and archaea, and in some bacteria.  In eukaryotes, they are located in the nucleus and the cytoplasm.  The main function of the proteasome is to degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks...

 degradation early post-infection. IRF3 degradation is dependent on the presence of NSP1 and the integrity of the N-terminal zinc-binding domain, coupled with the regulated stability of IRF3 and NSP1 by the proteasome, collectively support the hypothesis that NSP1 is an E3 ubiquitin ligase.

NSP1 could mediates the degradation of IRF3
IRF3
Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor.- Function :IRF3 is a member of the interferon regulatory transcription factor family. IRF3 was originally discovered as a homolog of IRF1 and IRF2...

, IRF5
IRF5
Interferon regulatory factor 5 is a protein that in humans is encoded by the IRF5 gene.- Function :IRF5 is a member of the interferon regulatory factor family, a group of transcription factors with diverse roles, including virus-mediated activation of interferon, and modulation of cell growth,...

, and IRF7
IRF7
Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors.-Further reading:- External links :...

 by recognizing a common element of IRF proteins, thereby allowing NSP1 to act as a broad-spectrum antagonist of IRF function.

NSP1 also inhibits activation of NFkappaB

NSP1 inhibits cellular apoptosis by activating PI3K/Akt survival pathway during early stages of rotavirus infection.
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