Early activation of MyD88-mediated autophagy sustains HSV-1 replication in human monocytic THP-1 cells.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Virus Replication*; Herpesvirus 1, Human/*physiology ; Myeloid Differentiation Factor 88/*metabolism ; Toll-Like Receptor 2/*metabolism; Adaptive Immunity ; Autophagy ; Herpesvirus 1, Human/genetics ; Humans ; Signal Transduction ; THP-1 Cells

Autophagy is a cellular degradation pathway that exerts numerous functions in vital biological processes. Among these, it contributes to both innate and adaptive immunity. On the other hand, pathogens have evolved strategies to manipulate autophagy for their own advantage. By monitoring autophagic markers, we showed that HSV-1 transiently induced autophagosome formation during early times of the infection of monocytic THP-1 cells and human monocytes. Autophagy is induced in THP-1 cells by a mechanism independent of viral gene expression or viral DNA accumulation. We found that the MyD88 signaling pathway is required for HSV-1-mediated autophagy, and it is linked to the toll-like receptor 2 (TLR2). Interestingly, autophagy inhibition by pharmacological modulators or siRNA knockdown impaired viral replication in both THP-1 cells and human monocytes, suggest that the virus exploits the autophagic machinery to its own benefit in these cells. Taken together, these findings indicate that the early autophagic response induced by HSV-1 exerts a proviral role, improving viral production in a semi-permissive model such as THP-1 cells and human monocytes.

J Virol. 2007 Oct;81(20):10924-32. (PMID: 17670820)
J Alzheimers Dis. 2012;30(4):815-31. (PMID: 22475795)
Nat Immunol. 2010 May;11(5):373-84. (PMID: 20404851)
Immunity. 2009 Apr 17;30(4):588-98. (PMID: 19362021)
Viral Immunol. 1991 Summer;4(2):91-102. (PMID: 1662046)
Proc Natl Acad Sci U S A. 2006 Nov 14;103(46):17343-8. (PMID: 17085599)
J Virol. 2013 Jan;87(2):859-71. (PMID: 23115300)
Cold Spring Harb Perspect Biol. 2014 May 01;6(5):a018358. (PMID: 24789822)
Immunity. 2007 Jul;27(1):135-44. (PMID: 17658277)
MBio. 2012 Oct 16;3(5):e00267-12. (PMID: 23073763)
J Virol. 2014 Jan;88(2):890-902. (PMID: 24198400)
Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):190-5. (PMID: 11756670)
Sci Rep. 2015 Apr 09;5:9730. (PMID: 25856282)
Sci Rep. 2015 Aug 07;5:12985. (PMID: 26248741)
J Gen Virol. 1997 Aug;78 ( Pt 8):1977-80. (PMID: 9266997)
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1315-20. (PMID: 14739339)
J Virol. 2014 Jan;88(1):434-43. (PMID: 24155402)
EBioMedicine. 2014 Nov 08;1(2-3):116-25. (PMID: 26137519)
J Virol. 2007 Nov;81(22):12128-34. (PMID: 17855538)
J Innate Immun. 2013;5(5):480-93. (PMID: 23391695)
J Exp Med. 2003 Aug 4;198(3):513-20. (PMID: 12900525)
J Immunol. 1984 Feb;132(2):936-44. (PMID: 6690624)
J Virol. 2012 Jun;86(12):6555-62. (PMID: 22496225)
Cell Host Microbe. 2007 Mar 15;1(1):23-35. (PMID: 18005679)
J Immunol. 2011 Nov 15;187(10):5268-76. (PMID: 21998456)
Autophagy. 2006 Jan-Mar;2(1):24-9. (PMID: 16874088)
J Biol Chem. 2008 Nov 28;283(48):33175-82. (PMID: 18772134)
Autophagy. 2008 Nov;4(8):998-1008. (PMID: 18818518)
EMBO J. 2008 Apr 9;27(7):1110-21. (PMID: 18337753)
Cell Host Microbe. 2009 Oct 22;6(4):354-66. (PMID: 19837375)
Nat Cell Biol. 2010 Aug;12 (8):747-57. (PMID: 20639872)
J Immunol. 2015 Oct 1;195(7):3045-57. (PMID: 26324779)
Cell Host Microbe. 2012 Sep 13;12(3):334-45. (PMID: 22980330)
J Gen Virol. 2010 Sep;91(Pt 9):2145-51. (PMID: 20505007)
Cell Res. 2010 Jul;20(7):748-62. (PMID: 20548331)
PLoS One. 2015 Apr 20;10(4):e0124646. (PMID: 25894397)
PLoS One. 2013;8(1):e54586. (PMID: 23382920)
Nat Immunol. 2009 May;10(5):480-7. (PMID: 19305394)
Virology. 1989 Apr;169(2):466-9. (PMID: 2539701)
J Clin Invest. 2006 Aug;116(8):2161-72. (PMID: 16886061)
Cell. 2011 Sep 30;147(1):223-34. (PMID: 21962518)
Immunity. 2012 Apr 20;36(4):658-67. (PMID: 22464169)
Proc Natl Acad Sci U S A. 2004 Aug 3;101(31):11416-21. (PMID: 15272082)
Methods Enzymol. 2009;452:1-12. (PMID: 19200872)
Blood. 2004 Feb 15;103(4):1433-7. (PMID: 14563635)
J Virol. 2013 Mar;87(6):3271-6. (PMID: 23302873)
Viral Immunol. 2011 Feb;24(1):11-26. (PMID: 21319975)

0 (MYD88 protein, human)
0 (Myeloid Differentiation Factor 88)
0 (TLR2 protein, human)
0 (Toll-Like Receptor 2)

Date Created: 20160812 Date Completed: 20180501 Latest Revision: 20181113

20231215

PMC4980660

10.1038/srep31302

27509841