A gammaherpesvirus complement regulatory protein promotes initiation of infection by activation of protein kinase Akt/PKB.

PloS One
Beatrix SteerHeiko Adler

Abstract

Viruses have evolved to evade the host's complement system. The open reading frames 4 (ORF4) of gammaherpesviruses encode homologs of regulators of complement activation (RCA) proteins, which inhibit complement activation at the level of C3 and C4 deposition. Besides complement regulation, these proteins are involved in heparan sulfate and glycosaminoglycan binding, and in case of MHV-68, also in viral DNA synthesis in macrophages. Here, we made use of MHV-68 to study the role of ORF4 during infection of fibroblasts. While attachment and penetration of virions lacking the RCA protein were not affected, we observed a delayed delivery of the viral genome to the nucleus of infected cells. Analysis of the phosphorylation status of a variety of kinases revealed a significant reduction in phosphorylation of the protein kinase Akt in cells infected with ORF4 mutant virus, when compared to cells infected with wt virus. Consistent with a role of Akt activation in initial stages of infection, inhibition of Akt signaling in wt virus infected cells resulted in a phenotype resembling the phenotype of the ORF4 mutant virus, and activation of Akt by addition of insulin partially reversed the phenotype of the ORF4 mutant virus. Importantly, th...Continue Reading

References

Aug 1, 1992·Journal of Virology·J C AlbrechtB Fleckenstein
Sep 1, 1991·Immunology Today·N R Cooper
Dec 10, 1996·Proceedings of the National Academy of Sciences of the United States of America·J J RussoP S Moore
Aug 1, 1997·Journal of Virology·H W VirginS H Speck
Feb 7, 1998·Proceedings of the National Academy of Sciences of the United States of America·M MesserleU H Koszinowski
Jan 7, 1998·Immunological Reviews·P J Lachmann, A Davies
May 2, 1998·Science·H L Ploegh
Jun 24, 1998·Proceedings of the National Academy of Sciences of the United States of America·A VanderplasschenG L Smith
Aug 10, 1999·Journal of Virology·S B KapadiaH W Virgin
Aug 23, 2000·Immunology Today·A Alcami, U H Koszinowski
Jun 8, 2001·Traffic·P S McPhersonN K Hussain
Dec 13, 2002·Journal of Virology·O Brad SpillerDavid J Blackbourn
Jan 30, 2004·Journal of Virology·Christine C Tomlinson, Blossom Damania
Mar 16, 2004·Virology·Clare E BlueDavid J Blackbourn
Apr 24, 2004·The Journal of General Virology·Samantha Cooray
Jul 21, 2004·Current Opinion in Cell Biology·Marta MiaczynskaMarino Zerial
Oct 6, 2005·Annals of Medicine·Vilja M PietiäinenTimo Hyypiä
Feb 10, 2006·Journal of Cell Science·Karine Lindmo, Harald Stenmark

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Citations

Apr 5, 2013·Biological Reviews of the Cambridge Philosophical Society·Eyal KamhiRobert J Linhardt
Jan 11, 2017·Particle and Fibre Toxicology·Christine SattlerTobias Stoeger
Sep 22, 2018·Scientific Reports·Hosni A M HusseinShaw M Akula

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Methods Mentioned

BETA
FACS
PCR
fluorescence microscopy
ELISAs
ELISA

Software Mentioned

CellQuestâ¢

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