Akt plays a critical role in replication of nonsegmented negative-stranded RNA viruses

Minghao Sun, Sandra M. Fuentes, Khalid A. Timani, Dengyun Sun, Chris Murphy, Yuan Lin, Avery August, Michael N. Teng, Biao He

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57 Citations (Scopus)

Abstract

The order Mononegavirales (comprised of nonsegmented negative-stranded RNA viruses or NNSVs) contains many important pathogens. Parainfluenza virus 5 (PIV5), formerly known as simian virus 5, is a prototypical paramyxovirus and encodes a V protein, which has a cysteine-rich C terminus that is conserved among all paramyxoviruses. The V protein of PIV5, like that of many other paramyxoviruses, plays an important role in regulating viral RNA synthesis. In this work, we show that V interacts with Akt, a serine/threonine kinase, also known as protein kinase B. Both pharmacological inhibitors and small interfering RNA against Aktl reduced PIV5 replication, indicating that Akt plays a critical role in PIV5 replication. Furthermore, treatment with Akt inhibitors also reduced the replication of several other paramyxoviruses, as well as vesicular stomatitis virus, the prototypical rhabdovirus, indicating that Akt may play a more universal role in NNSV replication. The phosphoproteins (P proteins) of NNSVs are essential cofactors for the viral RNA polymerase complex and require heavy phosphorylation for their activity. Inhibition of Akt activity reduced the level of P phosphorylation, suggesting that Akt is involved in regulating viral RNA synthesis. In addition, Aktl phosphorylated a recombinant P protein of PIV5 purified from bacteria. The finding that Akt plays a critical role in replication of NNSV will lead to a better understanding of how these viruses replicate, as well as novel strategies to treat infectious diseases caused by NNSVs.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalJournal of Virology
Volume82
Issue number1
DOIs
StatePublished - 1 Jan 2008

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Parainfluenza virus 5
Parainfluenza Virus 5
RNA Viruses
Respirovirus
Viral RNA
phosphoproteins
Phosphoproteins
Virus Replication
Mononegavirales
phosphorylation
Rhabdoviridae
Phosphorylation
RNA
Viruses
Vesiculovirus
Proto-Oncogene Proteins c-akt
Vesicular Stomatitis
synthesis
Protein-Serine-Threonine Kinases
DNA-Directed RNA Polymerases

Cite this

Sun, Minghao ; Fuentes, Sandra M. ; Timani, Khalid A. ; Sun, Dengyun ; Murphy, Chris ; Lin, Yuan ; August, Avery ; Teng, Michael N. ; He, Biao. / Akt plays a critical role in replication of nonsegmented negative-stranded RNA viruses. In: Journal of Virology. 2008 ; Vol. 82, No. 1. pp. 105-114.
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abstract = "The order Mononegavirales (comprised of nonsegmented negative-stranded RNA viruses or NNSVs) contains many important pathogens. Parainfluenza virus 5 (PIV5), formerly known as simian virus 5, is a prototypical paramyxovirus and encodes a V protein, which has a cysteine-rich C terminus that is conserved among all paramyxoviruses. The V protein of PIV5, like that of many other paramyxoviruses, plays an important role in regulating viral RNA synthesis. In this work, we show that V interacts with Akt, a serine/threonine kinase, also known as protein kinase B. Both pharmacological inhibitors and small interfering RNA against Aktl reduced PIV5 replication, indicating that Akt plays a critical role in PIV5 replication. Furthermore, treatment with Akt inhibitors also reduced the replication of several other paramyxoviruses, as well as vesicular stomatitis virus, the prototypical rhabdovirus, indicating that Akt may play a more universal role in NNSV replication. The phosphoproteins (P proteins) of NNSVs are essential cofactors for the viral RNA polymerase complex and require heavy phosphorylation for their activity. Inhibition of Akt activity reduced the level of P phosphorylation, suggesting that Akt is involved in regulating viral RNA synthesis. In addition, Aktl phosphorylated a recombinant P protein of PIV5 purified from bacteria. The finding that Akt plays a critical role in replication of NNSV will lead to a better understanding of how these viruses replicate, as well as novel strategies to treat infectious diseases caused by NNSVs.",
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Sun, M, Fuentes, SM, Timani, KA, Sun, D, Murphy, C, Lin, Y, August, A, Teng, MN & He, B 2008, 'Akt plays a critical role in replication of nonsegmented negative-stranded RNA viruses', Journal of Virology, vol. 82, no. 1, pp. 105-114. https://doi.org/10.1128/JVI.01520-07

Akt plays a critical role in replication of nonsegmented negative-stranded RNA viruses. / Sun, Minghao; Fuentes, Sandra M.; Timani, Khalid A.; Sun, Dengyun; Murphy, Chris; Lin, Yuan; August, Avery; Teng, Michael N.; He, Biao.

In: Journal of Virology, Vol. 82, No. 1, 01.01.2008, p. 105-114.

Research output: Contribution to journalArticleResearchpeer-review

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