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Recruitment and activation of a lipid kinase by hepatitis C virus NS5A is essential for integrity of the membranous replication compartment.

Reiss S, Rebhan I, Backes P, Romero-Brey I, Erfle H, Matula P, Kaderali L, Poenisch M, Blankenburg H, Hiet MS, Longerich T, Diehl S, Ramirez F, Balla T, Rohr K, Kaul A, Bühler S, Pepperkok R, Lengauer T, Albrecht M, Eils R, Schirmacher P, Lohmann V, Bartenschlager R.

Cell Host Microbe. 2011 Jan 20;9(1):32-45. doi: 10.1016/j.chom.2010.12.002.


Mapping of functional domains of the lipid kinase phosphatidylinositol 4-kinase type III alpha involved in enzymatic activity and hepatitis C virus replication.

Harak C, Radujkovic D, Taveneau C, Reiss S, Klein R, Bressanelli S, Lohmann V.

J Virol. 2014 Sep 1;88(17):9909-26. doi: 10.1128/JVI.01063-14. Epub 2014 Jun 11.


NS5A inhibitors impair NS5A-phosphatidylinositol 4-kinase IIIα complex formation and cause a decrease of phosphatidylinositol 4-phosphate and cholesterol levels in hepatitis C virus-associated membranes.

Reghellin V, Donnici L, Fenu S, Berno V, Calabrese V, Pagani M, Abrignani S, Peri F, De Francesco R, Neddermann P.

Antimicrob Agents Chemother. 2014 Dec;58(12):7128-40. doi: 10.1128/AAC.03293-14. Epub 2014 Sep 15.


The lipid kinase phosphatidylinositol-4 kinase III alpha regulates the phosphorylation status of hepatitis C virus NS5A.

Reiss S, Harak C, Romero-Brey I, Radujkovic D, Klein R, Ruggieri A, Rebhan I, Bartenschlager R, Lohmann V.

PLoS Pathog. 2013 May;9(5):e1003359. doi: 10.1371/journal.ppat.1003359. Epub 2013 May 9.


Hepatitis C virus stimulates the phosphatidylinositol 4-kinase III alpha-dependent phosphatidylinositol 4-phosphate production that is essential for its replication.

Berger KL, Kelly SM, Jordan TX, Tartell MA, Randall G.

J Virol. 2011 Sep;85(17):8870-83. doi: 10.1128/JVI.00059-11. Epub 2011 Jun 22.


Metabolism of phosphatidylinositol 4-kinase IIIα-dependent PI4P Is subverted by HCV and is targeted by a 4-anilino quinazoline with antiviral activity.

Bianco A, Reghellin V, Donnici L, Fenu S, Alvarez R, Baruffa C, Peri F, Pagani M, Abrignani S, Neddermann P, De Francesco R.

PLoS Pathog. 2012;8(3):e1002576. doi: 10.1371/journal.ppat.1002576. Epub 2012 Mar 8.


Daclatasvir-like inhibitors of NS5A block early biogenesis of hepatitis C virus-induced membranous replication factories, independent of RNA replication.

Berger C, Romero-Brey I, Radujkovic D, Terreux R, Zayas M, Paul D, Harak C, Hoppe S, Gao M, Penin F, Lohmann V, Bartenschlager R.

Gastroenterology. 2014 Nov;147(5):1094-105.e25. doi: 10.1053/j.gastro.2014.07.019. Epub 2014 Jul 18.


Hepatitis C virus NS5A protein interacts with phosphatidylinositol 4-kinase type IIIalpha and regulates viral propagation.

Lim YS, Hwang SB.

J Biol Chem. 2011 Apr 1;286(13):11290-8. doi: 10.1074/jbc.M110.194472. Epub 2011 Feb 5.


Daclatasvir inhibits hepatitis C virus NS5A motility and hyper-accumulation of phosphoinositides.

Chukkapalli V, Berger KL, Kelly SM, Thomas M, Deiters A, Randall G.

Virology. 2015 Feb;476:168-79. doi: 10.1016/j.virol.2014.12.018. Epub 2014 Dec 26.


Human Choline Kinase-α Promotes Hepatitis C Virus RNA Replication through Modulation of Membranous Viral Replication Complex Formation.

Wong MT, Chen SS.

J Virol. 2016 Sep 29;90(20):9075-95. doi: 10.1128/JVI.00960-16. Print 2016 Oct 15.


Evaluation of phosphatidylinositol-4-kinase IIIα as a hepatitis C virus drug target.

Vaillancourt FH, Brault M, Pilote L, Uyttersprot N, Gaillard ET, Stoltz JH, Knight BL, Pantages L, McFarland M, Breitfelder S, Chiu TT, Mahrouche L, Faucher AM, Cartier M, Cordingley MG, Bethell RC, Jiang H, White PW, Kukolj G.

J Virol. 2012 Nov;86(21):11595-607. doi: 10.1128/JVI.01320-12. Epub 2012 Aug 15.


Discovery of selective small molecule type III phosphatidylinositol 4-kinase alpha (PI4KIIIα) inhibitors as anti hepatitis C (HCV) agents.

Leivers AL, Tallant M, Shotwell JB, Dickerson S, Leivers MR, McDonald OB, Gobel J, Creech KL, Strum SL, Mathis A, Rogers S, Moore CB, Botyanszki J.

J Med Chem. 2014 Mar 13;57(5):2091-106. doi: 10.1021/jm400781h. Epub 2013 Aug 14.


Hepatitis C virus NS5A competes with PI4KB for binding to ACBD3 in a genotype-dependent manner.

Hong Z, Yang X, Yang G, Zhang L.

Antiviral Res. 2014 Jul;107:50-5. doi: 10.1016/j.antiviral.2014.04.012. Epub 2014 Apr 30.


Seed sequence-matched controls reveal limitations of small interfering RNA knockdown in functional and structural studies of hepatitis C virus NS5A-MOBKL1B interaction.

Chung HY, Gu M, Buehler E, MacDonald MR, Rice CM.

J Virol. 2014 Oct;88(19):11022-33. doi: 10.1128/JVI.01582-14. Epub 2014 Jul 16.


The role of the phosphatidylinositol 4-kinase PI4KA in hepatitis C virus-induced host membrane rearrangement.

Tai AW, Salloum S.

PLoS One. 2011;6(10):e26300. doi: 10.1371/journal.pone.0026300. Epub 2011 Oct 12.


Modulation of hepatitis C virus genome replication by glycosphingolipids and four-phosphate adaptor protein 2.

Khan I, Katikaneni DS, Han Q, Sanchez-Felipe L, Hanada K, Ambrose RL, Mackenzie JM, Konan KV.

J Virol. 2014 Nov;88(21):12276-95. doi: 10.1128/JVI.00970-14. Epub 2014 Aug 13.


Cytosolic phospholipase A2 gamma is involved in hepatitis C virus replication and assembly.

Xu S, Pei R, Guo M, Han Q, Lai J, Wang Y, Wu C, Zhou Y, Lu M, Chen X.

J Virol. 2012 Dec;86(23):13025-37. doi: 10.1128/JVI.01785-12. Epub 2012 Sep 26.


Hepatitis C virus NS5A hijacks ARFGAP1 to maintain a phosphatidylinositol 4-phosphate-enriched microenvironment.

Li H, Yang X, Yang G, Hong Z, Zhou L, Yin P, Xiao Y, Chen L, Chung RT, Zhang L.

J Virol. 2014 Jun;88(11):5956-66. doi: 10.1128/JVI.03738-13. Epub 2014 Mar 12.


Phosphorylation of NS5A Serine-235 is essential to hepatitis C virus RNA replication and normal replication compartment formation.

Eyre NS, Hampton-Smith RJ, Aloia AL, Eddes JS, Simpson KJ, Hoffmann P, Beard MR.

Virology. 2016 Apr;491:27-44. doi: 10.1016/j.virol.2016.01.018. Epub 2016 Feb 10.

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