Regulation of viral RNA synthesis by the V protein of parainfluenza virus 5

Yang Yang, James Zengel, Minghao Sun, Katrina Sleeman, Khalid A. Timani, Jason Aligo, Paul Rota, Jianguo Wu, Biao He

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the Nterminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses.

Original languageEnglish
Pages (from-to)11845-11857
Number of pages13
JournalJournal of Virology
Volume89
Issue number23
DOIs
StatePublished - 1 Jan 2015

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Parainfluenza virus 5
Parainfluenza Virus 5
Viral RNA
RNA
Respirovirus
synthesis
nucleocapsid proteins
Nucleocapsid Proteins
Proteins
proteins
viral proteins
Human parainfluenza virus 3
Mumps virus
Nipah Virus
Nipah virus
transcription (genetics)
Measles virus
genome
Respiratory Syncytial Viruses
Viral Genome

Cite this

Yang, Y., Zengel, J., Sun, M., Sleeman, K., Timani, K. A., Aligo, J., ... He, B. (2015). Regulation of viral RNA synthesis by the V protein of parainfluenza virus 5. Journal of Virology, 89(23), 11845-11857. https://doi.org/10.1128/JVI.01832-15
Yang, Yang ; Zengel, James ; Sun, Minghao ; Sleeman, Katrina ; Timani, Khalid A. ; Aligo, Jason ; Rota, Paul ; Wu, Jianguo ; He, Biao. / Regulation of viral RNA synthesis by the V protein of parainfluenza virus 5. In: Journal of Virology. 2015 ; Vol. 89, No. 23. pp. 11845-11857.
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title = "Regulation of viral RNA synthesis by the V protein of parainfluenza virus 5",
abstract = "Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the Nterminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses.",
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Yang, Y, Zengel, J, Sun, M, Sleeman, K, Timani, KA, Aligo, J, Rota, P, Wu, J & He, B 2015, 'Regulation of viral RNA synthesis by the V protein of parainfluenza virus 5', Journal of Virology, vol. 89, no. 23, pp. 11845-11857. https://doi.org/10.1128/JVI.01832-15

Regulation of viral RNA synthesis by the V protein of parainfluenza virus 5. / Yang, Yang; Zengel, James; Sun, Minghao; Sleeman, Katrina; Timani, Khalid A.; Aligo, Jason; Rota, Paul; Wu, Jianguo; He, Biao.

In: Journal of Virology, Vol. 89, No. 23, 01.01.2015, p. 11845-11857.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Yang, Yang

AU - Zengel, James

AU - Sun, Minghao

AU - Sleeman, Katrina

AU - Timani, Khalid A.

AU - Aligo, Jason

AU - Rota, Paul

AU - Wu, Jianguo

AU - He, Biao

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N2 - Paramyxoviruses include many important animal and human pathogens. The genome of parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, encodes a V protein that inhibits viral RNA synthesis. In this work, the mechanism of inhibition was investigated. Using mutational analysis and a minigenome system, we identified regions in the N and C termini of the V protein that inhibit viral RNA synthesis: one at the very N terminus of V and the second at the C terminus of V. Furthermore, we determined that residues L16 and I17 are critical for the inhibitory function of the N-terminal region of the V protein. Both regions interact with the nucleocapsid protein (NP), an essential component of the viral RNA genome complex (RNP). Mutations at L16 and I17 abolished the interaction between NP and the N-terminal domain of V. This suggests that the interaction between NP and the N-terminal domain plays a critical role in V inhibition of viral RNA synthesis by the N-terminal domain. Both the N- and C-terminal regions inhibited viral RNA replication. The C terminus inhibited viral RNA transcription, while the Nterminal domain enhanced viral RNA transcription, suggesting that the two domains affect viral RNA through different mechanisms. Interestingly, V also inhibited the synthesis of the RNA of other paramyxoviruses, such as Nipah virus (NiV), human parainfluenza virus 3 (HPIV3), measles virus (MeV), mumps virus (MuV), and respiratory syncytial virus (RSV). This suggests that a common host factor may be involved in the replication of these paramyxoviruses.

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