N-terminally truncated C protein, CNDelta25, of human parainfluenza virus type 3 is a potent inhibitor of viral replication.
The C protein of human parainfluenza virus type 3 (HPIV3) is a multifunctional accessory protein that inhibits viral transcription and interferon (IFN) signaling. In the present study, we found that removal of N-terminal 25 or 50 amino acid residues from the C protein (CNDelta25 or CNDelta50) totally abolished viral RNA synthesis in the HPIV3 minigenome system. Further N-terminal or C-terminal deletion impaired the inhibitory ability of CNDelta25 and CNDelta50. Subsequent mutagenesis analysis suggested that the N-terminal-charged amino acid residues (K3, K6, K12, E16, and R24) contribute to the higher inhibition caused by CNDelta25 than the C protein. Consistent with viral RNA synthesis inhibition, the growth of HPIV3 was significantly decreased by 5 logs in HeLa-derived cell line expressing CNDelta25. Interestingly, replication of respiratory syncytial virus (RSV), another important respiratory tract pathogen, was also strongly inhibited in the presence of CNDelta25. These findings provide a promising potential to use CNDelta25 as an antiviral agent against the clinically important respiratory tract diseases caused by HPIV3 and RSV.
Mao
Hongxia
H
Virology Section, Department of Molecular Genetics, Lerner Research Institute, Cleveland Clinic Foundation, NN1-06, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Chattopadhyay
Santanu
S
Banerjee
Amiya K
AK
D000998:Antiviral Agents / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D050505:Mutant Proteins / Q000235:genetics / Q000494:pharmacology; D010224:Parainfluenza Virus 3, Human / Q000187:drug effects / Q000502:physiology*; D012367:RNA, Viral / Q000096:biosynthesis; D012136:Respiratory Syncytial Viruses / Q000502:physiology; D017384:Sequence Deletion; D014764:Viral Proteins / Q000235:genetics* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D000998:Antiviral Agents; D050505:Mutant Proteins; D012367:RNA, Viral; D014764:Viral Proteins