NSP1 (NS53), the product of

rotavirus ''Rotavirus'' is a genus of double-stranded RNA viruses in the family ''Reoviridae''. Rotaviruses are the most common cause of diarrhoeal disease among infants and young children. Nearly every child in the world is infected with a rotavirus a ...

gene 5, is a nonstructural RNA-binding protein that contains a cysteine-rich region and is a component of early replication intermediates. RNA-

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predictions suggest that this region of the NSP1

mRNA In molecular biology, messenger ribonucleic acid (mRNA) is a single-stranded molecule of RNA that corresponds to the genetic sequence of a gene, and is read by a ribosome in the process of Protein biosynthesis, synthesizing a protein. mRNA is ...

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

. The carboxyl-half of the

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 Interferon regulatory factor 3, also known as IRF3, is an interferon regulatory factor. Function IRF3 is a member of the interferon regulatory transcription factor (IRF) 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 (

) 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 Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks peptide bonds. Enzymes that help such reactions are called proteases. Proteasomes are part of a major mechanism by w ...

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

IRF5 Interferon regulatory factor 5 is a protein that in humans is encoded by the ''IRF5'' gene. The IRF family is a group of transcription factors that are involved in signaling for virus responses in mammals along with regulation of certain cellular ...

, and

IRF7 Interferon regulatory factor 7, also known as IRF7, is a member of the interferon regulatory factor family of transcription factors. Function IRF7 encodes interferon regulatory factor 7, a member of the interferon regulatory transcription fact ...

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 directly interacting p85 subunit of PI3K and thus activating PI3K/Akt survival pathway during early stages of rotavirus infection.

References

{{Viral proteins Amino acid motifs Mutation Rotaviruses Viral nonstructural proteins