OR14I1 is a receptor for the human cytomegalovirus pentameric complex and defines viral epithelial cell tropism.
CRISPR screen
OR14I1
human cytomegalovirus
pentameric glycoprotein complex
virus receptor
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
02 04 2019
02 04 2019
Historique:
pubmed:
22
3
2019
medline:
22
5
2019
entrez:
22
3
2019
Statut:
ppublish
Résumé
A human cytomegalovirus (HCMV) pentameric glycoprotein complex (PC), gH-gL-UL128-UL130-UL131A, is necessary for viral infection of clinically relevant cell types, including epithelial cells, which are important for interhost transmission and disease. We performed genome-wide CRISPR/Cas9 screens of different cell types in parallel to identify host genes specifically required for HCMV infection of epithelial cells. This effort identified a multipass membrane protein, OR14I1, as a receptor for HCMV infection. This olfactory receptor family member is required for HCMV attachment, entry, and infection of epithelial cells and is dependent on the presence of viral PC. OR14I1 is required for AKT activation and mediates endocytosis entry of HCMV. We further found that HCMV infection of epithelial cells is blocked by a synthetic OR14I1 peptide and inhibitors of adenylate cyclase and protein kinase A (PKA) signaling. Identification of OR14I1 as a PC-dependent HCMV host receptor associated with epithelial tropism and the role of the adenylate cyclase/PKA/AKT-mediated signaling pathway in HCMV infection reveal previously unappreciated targets for the development of vaccines and antiviral therapies.
Identifiants
pubmed: 30894498
pii: 1814850116
doi: 10.1073/pnas.1814850116
pmc: PMC6452726
doi:
Substances chimiques
Multiprotein Complexes
0
Viral Proteins
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Cyclic AMP-Dependent Protein Kinases
EC 2.7.11.11
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7043-7052Subventions
Organisme : NIAID NIH HHS
ID : P01 AI127335
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM103433
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI056077
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI109001
Pays : United States
Informations de copyright
Copyright © 2019 the Author(s). Published by PNAS.
Déclaration de conflit d'intérêts
Conflict of interest statement: X.E., A.L.B., and T.F.K. are listed as coinventors in a patent application based in part on data from this study.
Références
Invest Ophthalmol Vis Sci. 1999 Oct;40(11):2598-607
pubmed: 10509655
Neuron. 2000 Sep;27(3):487-97
pubmed: 11055432
J Virol. 2002 Mar;76(5):2316-28
pubmed: 11836410
J Virol. 2003 May;77(9):5324-32
pubmed: 12692234
J Virol. 2003 May;77(10):5712-20
pubmed: 12719564
Nature. 2003 Jul 24;424(6947):456-61
pubmed: 12879076
EMBO J. 2003 Sep 1;22(17):4346-55
pubmed: 12941687
Virology. 1992 Nov;191(1):387-95
pubmed: 1329327
Microsc Res Tech. 1992 Oct 15;23(2):128-41
pubmed: 1421552
Trends Cell Biol. 2004 Jan;14(1):5-8
pubmed: 14729174
Microbes Infect. 2004 Aug;6(10):929-36
pubmed: 15310470
J Virol. 2004 Sep;78(18):10023-33
pubmed: 15331735
J Gen Virol. 2005 Feb;86(Pt 2):275-84
pubmed: 15659746
Nat Med. 2005 May;11(5):515-21
pubmed: 15834425
J Neurovirol. 2005 Apr;11(2):129-37
pubmed: 16036791
J Virol. 2005 Aug;79(16):10330-8
pubmed: 16051825
J Virol. 2005 Dec;79(23):14482-8
pubmed: 16282447
Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18153-8
pubmed: 16319222
J Virol. 2006 Jan;80(2):710-22
pubmed: 16378974
Nat Methods. 2006 Oct;3(10):777-9
pubmed: 16990807
J Virol. 2007 May;81(9):4701-12
pubmed: 17314173
J Virol. 2007 Jun;81(12):6241-7
pubmed: 17428848
Rev Med Virol. 2007 Sep-Oct;17(5):355-63
pubmed: 17542052
Rev Med Virol. 2007 Jul-Aug;17(4):253-76
pubmed: 17579921
Curr Top Microbiol Immunol. 2008;325:63-83
pubmed: 18637500
Curr Top Microbiol Immunol. 2008;325:417-70
pubmed: 18637519
Nature. 2008 Sep 18;455(7211):391-5
pubmed: 18701889
Mol Biol Evol. 2009 Mar;26(3):491-4
pubmed: 19103638
Hum Genomics. 2008 Sep;3(1):87-97
pubmed: 19129093
J Immunol. 2009 Feb 1;182(3):1548-59
pubmed: 19155503
J Gen Virol. 2009 Mar;90(Pt 3):602-13
pubmed: 19218205
Proc Natl Acad Sci U S A. 2009 Dec 29;106(52):22369-74
pubmed: 20018733
J Virol. 2010 Mar;84(5):2585-96
pubmed: 20032184
J Cell Biol. 2010 Nov 1;191(3):443-52
pubmed: 21041441
PLoS Pathog. 2011 May;7(5):e1001342
pubmed: 21589897
Curr Protoc Microbiol. 2012 Feb;Chapter 14:Unit14E.4
pubmed: 22307551
Curr Opin Virol. 2012 Feb;2(1):37-42
pubmed: 22440964
Eye (Lond). 2012 Aug;26(8):1152
pubmed: 22627483
PLoS Pathog. 2012 Sep;8(9):e1002905
pubmed: 23028311
Mol Biosyst. 2013 Apr 5;9(4):586-95
pubmed: 23247090
Proc Natl Acad Sci U S A. 2013 Mar 12;110(11):4410-5
pubmed: 23401498
MBio. 2013 Jun 04;4(3):e00332-13
pubmed: 23736286
Cell Rep. 2013 Aug 29;4(4):659-68
pubmed: 23954786
J Virol. 2014 Feb;88(4):2279-90
pubmed: 24335308
Science. 2014 Jan 3;343(6166):84-87
pubmed: 24336571
J Virol. 2014 Dec;88(24):14030-9
pubmed: 25253348
PLoS Pathog. 2015 Jul 06;11(7):e1004999
pubmed: 26147640
Cell Rep. 2015 Aug 4;12(5):850-63
pubmed: 26212330
Mol Biol Evol. 2015 Nov;32(11):2832-43
pubmed: 26219582
Adv Virus Res. 2016;94:1-51
pubmed: 26997589
J Exp Biol. 2016 Jun 15;219(Pt 12):1798-803
pubmed: 27045092
MBio. 2016 Apr 26;7(2):e00251-16
pubmed: 27118588
Cell Rep. 2016 Jun 28;16(1):232-246
pubmed: 27342126
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):8819-24
pubmed: 27432979
Front Aging Neurosci. 2016 Jul 05;8:163
pubmed: 27458372
Annu Rev Virol. 2016 Sep 29;3(1):215-236
pubmed: 27501260
J Virol. 2016 Oct 14;90(21):9766-9781
pubmed: 27558416
Nature. 2016 Oct 20;538(7625):350-355
pubmed: 27680706
Sci Rep. 2016 Oct 14;6:35215
pubmed: 27739476
Proc Natl Acad Sci U S A. 1989 Jul;86(14):5641-5
pubmed: 2787513
J Virol. 2017 Feb 14;91(5):
pubmed: 27974567
Biomol Ther (Seoul). 2017 Jan 1;25(1):12-25
pubmed: 28035079
J Virol. 2017 May 26;91(12):
pubmed: 28381570
PLoS Pathog. 2017 Apr 12;13(4):e1006281
pubmed: 28403202
J Neuroinflammation. 2017 Jun 23;14(1):124
pubmed: 28645309
MBio. 2018 May 8;9(3):
pubmed: 29739904
Cell. 2018 Aug 23;174(5):1158-1171.e19
pubmed: 30057110
Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9889-E9898
pubmed: 30275317
Biochim Biophys Acta. 1984 May 22;804(1):58-67
pubmed: 6722184
Adv Virus Res. 1996;46:195-261
pubmed: 8824701
Neuron. 1998 Jan;20(1):69-81
pubmed: 9459443
Ann N Y Acad Sci. 1998 Nov 30;855:751-61
pubmed: 9929681