The N-terminal fragment of PA subunit of the influenza A virus effectively inhibits ribonucleoprotein (RNP) activity via suppression of its RNP expression

Abstract The influenza RNP, which is formed from PB1, PB2, PA, NP subunits, and vRNA, is autonomously replicated and transcribed in the infected cell. The simplest method to inhibit RNP activity is to impair the formation of the RNP. Thereupon we confirmed whether the peptides/fragments mimicking on...

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Bibliographic Details
Published in:Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2015-04, Vol.21 (4), p.296-301
Main Authors: Uemura, Yusaku, Kashiwagi, Takahito, Hara, Koyu, Nakazono, Yoko, Hamada, Nobuyuki, Watanabe, Hiroshi
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Amino Acids - chemistry
Hematology, Oncology and Palliative Medicine
Influenza A virus
Influenza A virus - genetics
Influenza A virus - metabolism
Inhibitor
PA subunit
Protein Subunits - chemistry
Protein Subunits - metabolism
Ribonucleoprotein
Ribonucleoproteins - antagonists & inhibitors
Ribonucleoproteins - chemistry
Ribonucleoproteins - metabolism
RNA polymerase
Sequence Alignment
Viral Proteins - antagonists & inhibitors
Viral Proteins - chemistry
Viral Proteins - metabolism
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Summary:Abstract The influenza RNP, which is formed from PB1, PB2, PA, NP subunits, and vRNA, is autonomously replicated and transcribed in the infected cell. The simplest method to inhibit RNP activity is to impair the formation of the RNP. Thereupon we confirmed whether the peptides/fragments mimicking one of RNP components can interfere with their formation. During the process of this inhibitory study we found interesting suppression of protein expression of the RNP components by the N-terminal fragment of PA subunit. Especially, we found two residues (D108 and K134) on the fragment that were critical for the suppression. Furthermore, we determined the combination of three amino acids (P28, M86 and E100) on the fragment that are important for the strong suppression, and identified the minimum essential region (residues from 1 to 188) of the PA subunit that allowed its suppression. Our findings indicate that the N-terminal fragment of PA subunit may become one of candidates for an effective inhibitor of influenza RNP activity.
ISSN:1341-321X
1437-7780
DOI:10.1016/j.jiac.2014.12.007