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

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

Research output: Contribution to journalArticle

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

    Fingerprint

Cite this

Yang, Y., Zengel, J., Sun, M., Sleeman, K., Timani, K. A., 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, 89(23), 11845-11857. https://doi.org/10.1128/JVI.01832-15