title: Viral infection of the lung: host response and sequelae.
abstract: Because of its essential role in gas exchange and oxygen delivery, the lung has evolved a variety of strategies to control inflammation and maintain homeostasis. Invasion of the lung by pathogens (and in some instances exposure to certain noninfectious particulates) disrupts this equilibrium and triggers a cascade of events aimed at preventing or limiting colonization (and more importantly infection) by pathogenic microorganisms. In this review we focus on viral infection of the lung and summarize recent advances in our understanding of the triggering of innate and adaptive immune responses to viral respiratory tract infection, mechanisms of viral clearance, and the well-recognized consequences of acute viral infection complicating underlying lung diseases, such as asthma.
authors.affiliation: Beirne B. Carter Center for Immunology Research, University of Virginia, Charlottesville, Va.
authors.forename: Jae-Kwang
authors.initials: JK
authors.lastname: Yoo
authors.forename: Taeg S
authors.initials: TS
authors.lastname: Kim
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Hufford
authors.forename: Thomas J
authors.initials: TJ
authors.lastname: Braciale
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001249:Asthma / Q000276:immunology* / Q000503:physiopathology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007113:Immunity, Innate; D008168:Lung / Q000276:immunology* / Q000821:virology; D011024:Pneumonia, Viral / Q000276:immunology*
keywords: AIM2; APC; ASC; Absent in melanoma 2; Antigen-presenting cell; Apoptosis-associated speck-like protein containing CARD; B-cell immunity; CTL; Cytotoxic CD8(+) T-cell; DAMP; DC; Damage-associated molecular pattern; Dendritic cell; Follicular helper T; GC; Germinal center; HMGB1; High-mobility group box 1; IAV; ILC; ILC-II; IRF; Influenza A virus; Innate lymphoid cell; Interferon regulatory factor; LAPC; Late activator antigen-presenting cell; MAVS; MLN; Mediastinal lymph node; Mitochondrial anti-viral signaling; NK; NLRP3; Natural killer; Nod-like receptor family protein 3; PAMP; PRR; Pathogen-associated molecular pattern; Pattern recognition receptor; RIG-I; RIG-I–like receptor; RLR; RSV; Regulatory T; Respiratory syncytial virus; Retinoic acid–inducible gene I; T(FH); T-cell immunity; TLR; Toll-like receptor; Treg; Type II innate lymphoid cell; Viral sensor molecules; adaptive immunity; innate immunity; stem cells; tissue repair; viral clearance
references.citation: Mucosal Immunol. 2013 Jan;6(1):69-82
references.pmid: 22739232
references.citation: Nat Med. 2012 May 04;18(5):726-35
references.pmid: 22561836
references.citation: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13562-7
references.pmid: 18768794
references.citation: Immunity. 2008 Jul 18;29(1):138-49
references.pmid: 18599325
references.citation: J Virol. 2010 Oct;84(19):10191-9
references.pmid: 20660207
references.citation: Trends Immunol. 2011 Jan;32(1):34-41
references.pmid: 21147034
references.citation: J Exp Med. 2010 Jul 5;207(7):1435-51
references.pmid: 20547825
references.citation: Nat Immunol. 2011 May 29;12(7):631-8
references.pmid: 21623379
references.citation: J Allergy Clin Immunol. 2007 May;119(5):1105-10
references.pmid: 17353039
references.citation: Immunity. 2011 Jan 28;34(1):108-21
references.pmid: 21215658
references.citation: Cell Stem Cell. 2009 Jun 5;4(6):525-34
references.pmid: 19497281
references.citation: BMJ. 1995 May 13;310(6989):1225-9
references.pmid: 7767192
references.citation: Nature. 2010 Apr 29;464(7293):1367-70
references.pmid: 20200518
references.citation: Mucosal Immunol. 2010 Jan;3(1):69-80
references.pmid: 19710636
references.citation: Eur Respir J. 2002 May;19(5):899-905
references.pmid: 12030731
references.citation: Virology. 2010 Sep 1;404(2):225-30
references.pmid: 20627346
references.citation: J Exp Med. 2008 Jul 7;205(7):1635-46
references.pmid: 18591411
references.citation: Nat Rev Immunol. 2005 Nov;5(11):853-65
references.pmid: 16261173
references.citation: J Immunol. 2004 Jun 15;172(12):7603-9
references.pmid: 15187140
references.citation: PLoS One. 2012;7(11):e50385
references.pmid: 23185614
references.citation: Am J Pathol. 2002 Jul;161(1):173-82
references.pmid: 12107102
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Aug;289(2):L274-9
references.pmid: 15833765
references.citation: J Exp Med. 2010 Apr 12;207(4):823-36
references.pmid: 20351058
references.citation: Proc Am Thorac Soc. 2008 Apr 15;5(3):323-7
references.pmid: 18403327
references.citation: Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12771-5
references.pmid: 19625615
references.citation: J Pediatr. 1980 Feb;96(2):179-86
references.pmid: 6243354
references.citation: Nat Med. 2008 Mar;14(3):282-9
references.pmid: 18264109
references.citation: Nat Immunol. 2011 Jan;12(1):21-7
references.pmid: 21113163
references.citation: Trends Immunol. 2011 Jul;32(7):328-34
references.pmid: 21612981
references.citation: Infect Immun. 2005 Apr;73(4):1907-16
references.pmid: 15784530
references.citation: Am J Respir Cell Mol Biol. 2010 Apr;42(4):450-60
references.pmid: 19520922
references.citation: Am J Pathol. 2010 Jul;177(1):362-76
references.pmid: 20522644
references.citation: Clin Infect Dis. 2005 Aug 1;41(3):345-51
references.pmid: 16007532
references.citation: Nat Immunol. 2011 Sep 11;12(11):1055-62
references.pmid: 21909091
references.citation: Trends Immunol. 2006 Aug;27(8):352-7
references.pmid: 16807108
references.citation: Cell. 2005 Jun 17;121(6):823-35
references.pmid: 15960971
references.citation: Semin Immunopathol. 2010 Jun;32(2):183-96
references.pmid: 20107805
references.citation: Nat Immunol. 2008 Sep;9(9):1074-83
references.pmid: 18660812
references.citation: J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):915-20
references.pmid: 9847431
references.citation: Am Rev Respir Dis. 1986 Nov;134(5):1040-4
references.pmid: 3777666
references.citation: PLoS Pathog. 2011 May;7(5):e1002003
references.pmid: 21589896
references.citation: PLoS Pathog. 2006 Jun;2(6):e53
references.pmid: 16789835
references.citation: Nature. 2003 Oct 2;425(6957):516-21
references.pmid: 14520412
references.citation: Nat Med. 2006 Sep;12(9):1023-6
references.pmid: 16906156
references.citation: J Virol. 2010 Aug;84(15):7750-9
references.pmid: 20504940
references.citation: Cell. 2011 Oct 28;147(3):525-38
references.pmid: 22036562
references.citation: Immunol Cell Biol. 2007 Feb-Mar;85(2):85-92
references.pmid: 17213831
references.citation: J Immunol. 2011 Sep 15;187(6):3145-54
references.pmid: 21844390
references.citation: Immunol Rev. 2009 Jan;227(1):54-65
references.pmid: 19120475
references.citation: J Immunol. 2007 Sep 15;179(6):3926-36
references.pmid: 17785830
references.citation: Annu Rev Immunol. 2011;29:621-63
references.pmid: 21314428
references.citation: J Immunol. 2012 Jun 1;188(11):5682-93
references.pmid: 22523386
references.citation: Immunity. 2009 Apr 17;30(4):556-65
references.pmid: 19362020
references.citation: J Immunol. 2007 Feb 15;178(4):2182-91
references.pmid: 17277123
references.citation: Nat Med. 2009 Mar;15(3):277-84
references.pmid: 19234462
references.citation: Nat Immunol. 2011 Nov;12(11):1045-54
references.pmid: 21946417
references.citation: Proc Natl Acad Sci U S A. 2010 Dec 28;107(52):22587-92
references.pmid: 21149737
references.citation: J Exp Med. 2000 Dec 4;192(11):1553-62
references.pmid: 11104798
references.citation: J Exp Med. 1994 Oct 1;180(4):1273-82
references.pmid: 7931062
references.citation: Immunity. 2012 Mar 23;36(3):451-63
references.pmid: 22425247
references.citation: Virology. 2011 Mar 15;411(2):362-73
references.pmid: 21292294
references.citation: Nature. 2013 Jan 24;493(7433):547-51
references.pmid: 23235830
references.citation: Nat Med. 2002 Apr;8(4):373-8
references.pmid: 11927943
references.citation: J Immunol. 2008 Feb 15;180(4):2562-72
references.pmid: 18250467
references.citation: Nat Med. 2004 Aug;10(8):811-3
references.pmid: 15247911
references.citation: Mucosal Immunol. 2010 May;3(3):291-300
references.pmid: 20404812
references.citation: Comp Med. 2007 Feb;57(1):82-9
references.pmid: 17348295
references.citation: J Immunol. 2010 Aug 15;185(4):2382-92
references.pmid: 20639494
references.citation: Clin Exp Immunol. 1986 Jun;64(3):503-9
references.pmid: 3791688
references.citation: J Virol. 2010 Sep;84(17):8790-8
references.pmid: 20573822
references.citation: J Immunol. 1996 Oct 1;157(7):2947-52
references.pmid: 8816401
references.citation: Nat Med. 2008 Jun;14(6):633-40
references.pmid: 18488036
references.citation: J Exp Med. 2008 Feb 18;205(2):323-9
references.pmid: 18227219
references.citation: Nat Immunol. 2010 Jan;11(1):63-9
references.pmid: 19915568
references.citation: J Allergy Clin Immunol. 2010 Mar;125(3):653-9, 659.e1-659.e7
references.pmid: 20226300
references.citation: PLoS Pathog. 2011 Aug;7(8):e1002173
references.pmid: 21829368
references.citation: J Exp Med. 2006 May 15;203(5):1153-9
references.pmid: 16682497
references.citation: Immunity. 2011 Jun 24;34(6):932-46
references.pmid: 21636296
references.citation: J Exp Med. 2012 Sep 24;209(10):1853-67
references.pmid: 22987801
references.citation: J Interferon Cytokine Res. 2010 Aug;30(8):555-64
references.pmid: 20712453
references.citation: Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9286-91
references.pmid: 19478060
references.citation: J Exp Med. 2011 Jul 4;208(7):1377-88
references.pmid: 21708925
references.citation: J Clin Invest. 2011 Jun;121(6):2065-73
references.pmid: 21633173
references.citation: Curr Opin Virol. 2012 Jun;2(3):233-41
references.pmid: 22608464
references.citation: JAMA. 1961 May 27;176:647-53
references.pmid: 13692354
references.citation: J Immunol. 2011 Apr 1;186(7):3823-9
references.pmid: 21422252
references.citation: J Virol. 1998 Jan;72(1):882-5
references.pmid: 9420305
references.citation: J Clin Invest. 2009 Jul;119(7):1910-20
references.pmid: 19487810
references.citation: Curr Opin Immunol. 2010 Feb;22(1):41-7
references.pmid: 20061127
references.citation: J Virol. 1998 May;72(5):4498-502
references.pmid: 9557748
references.citation: J Immunol. 2008 Feb 1;180(3):1749-57
references.pmid: 18209072
references.citation: Curr Opin Immunol. 2001 Feb;13(1):114-9
references.pmid: 11154927
references.citation: PLoS Pathog. 2009 Dec;5(12):e1000510
references.pmid: 20041168
references.citation: PLoS One. 2009;4(1):e4204
references.pmid: 19145246
references.citation: Immunol Rev. 2009 Jan;227(1):75-86
references.pmid: 19120477
references.citation: Thorax. 2008 Jan;63(1):42-8
references.pmid: 17573440
references.citation: J Exp Med. 1988 Sep 1;168(3):1163-8
references.pmid: 3262705
references.citation: PLoS One. 2012;7(4):e35812
references.pmid: 22558229
references.citation: PLoS Pathog. 2010 Oct 07;6(10):e1001136
references.pmid: 20949074
references.citation: J Immunol. 2009 Aug 15;183(4):2793-800
references.pmid: 19620293
references.citation: Nature. 2010 Jan 28;463(7280):540-4
references.pmid: 20023630
references.citation: Nat Med. 2012 Jan 15;18(2):260-6
references.pmid: 22245779
references.citation: Nature. 2009 Mar 26;458(7237):514-8
references.pmid: 19158675
references.citation: J Exp Med. 2001 Jun 18;193(12):1373-81
references.pmid: 11413192
references.citation: Sci Signal. 2009 Feb 03;2(56):pe6
references.pmid: 19193605
references.citation: Virus Res. 1985 Oct;3(3):193-206
references.pmid: 3907188
references.citation: Pediatr Allergy Immunol. 2011 Feb;22(1 Pt 2):e119-23
references.pmid: 21342277
references.citation: Pediatr Infect Dis J. 2006 Aug;25(8):680-6
references.pmid: 16874165
references.citation: J Exp Med. 2000 Dec 4;192(11):1545-52
references.pmid: 11104797
references.citation: Immunity. 2009 Apr 17;30(4):566-75
references.pmid: 19362023
references.citation: Microbiol Mol Biol Rev. 2012 Mar;76(1):16-32
references.pmid: 22390970
references.citation: J Exp Med. 2009 Jan 16;206(1):79-87
references.pmid: 19139171
references.citation: Nat Immunol. 2001 Dec;2(12):1144-50
references.pmid: 11713464
references.citation: J Gen Virol. 2005 Jan;86(Pt 1):185-195
references.pmid: 15604446
references.citation: Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11489-94
references.pmid: 20534524
references.citation: Nat Rev Immunol. 2008 Feb;8(2):142-52
references.pmid: 18204469
references.citation: J Virol. 2009 Apr;83(7):3019-28
references.pmid: 19153229
references.citation: Eur J Immunol. 2001 Mar;31(3):726-33
references.pmid: 11241276
references.citation: J Allergy Clin Immunol. 2005 Sep;116(3):571-7
references.pmid: 16159626
references.citation: J Immunol. 2007 Feb 15;178(4):2448-57
references.pmid: 17277152
references.citation: J Immunol. 1999 Jun 15;162(12):7322-9
references.pmid: 10358182
references.citation: Vaccine. 2011 Oct 6;29(43):7524-8
references.pmid: 21820476
references.citation: PLoS One. 2009 Sep 28;4(9):e7187
references.pmid: 19784375
references.citation: J Infect Dis. 1978 Jul;138(1):24-32
references.pmid: 355574
references.citation: Nat Rev Immunol. 2005 May;5(5):375-86
references.pmid: 15864272
references.citation: Curr Opin Neurol. 2010 Jun;23(3):305-11
references.pmid: 20455276
references.citation: PLoS One. 2012;7(9):e45842
references.pmid: 23029269
references.citation: Am J Respir Crit Care Med. 2000 May;161(5):1501-7
references.pmid: 10806145
references.citation: PLoS Pathog. 2013 Jan;9(1):e1003115
references.pmid: 23326231
references.citation: Eur J Immunol. 2011 Sep;41(9):2632-41
references.pmid: 21660939
references.citation: J Allergy Clin Immunol. 2009 Sep;124(3):463-70, 470.e1-16
references.pmid: 19733295
references.citation: Lancet. 1999 Aug 14;354(9178):541-5
references.pmid: 10470697
references.citation: Antiviral Res. 2010 Oct;88(1):64-71
references.pmid: 20659503
references.citation: J Virol. 1985 Oct;56(1):55-9
references.pmid: 2411951
references.citation: Nat Immunol. 2013 Mar;14(3):246-53
references.pmid: 23314004
references.citation: Int J Cardiol. 2008 Nov 28;130(3):304-9
references.pmid: 18625525
references.citation: Br Med J (Clin Res Ed). 1982 Jun 5;284(6330):1665-9
references.pmid: 6805648
references.citation: J Immunol. 2007 Oct 1;179(7):4711-20
references.pmid: 17878370
references.citation: N Engl J Med. 2011 Mar 17;364(11):1005-15
references.pmid: 21410369
references.citation: J Biol Chem. 2006 Dec 1;281(48):36560-8
references.pmid: 17008311
references.citation: Nat Rev Immunol. 2012 Mar 09;12(4):295-305
references.pmid: 22402670
references.citation: J Allergy Clin Immunol. 2010 May;125(5):1001-1006.e1
references.pmid: 20392488
references.citation: Immunobiology. 2009;214(7):630-41
references.pmid: 19264378
references.citation: Am J Physiol Lung Cell Mol Physiol. 2010 Jun;298(6):L715-31
references.pmid: 20363851
references.citation: Lancet. 2008 Sep 20;372(9643):1058-64
references.pmid: 18805334
references.citation: Nature. 2008 Mar 6;452(7183):103-7
references.pmid: 18288107
references.citation: J Infect Dis. 1985 Nov;152(5):1083-7
references.pmid: 4045247
references.citation: J Exp Med. 2011 Jan 17;208(1):167-80
references.pmid: 21187318
references.citation: Immunity. 2008 Jul 18;29(1):127-37
references.pmid: 18602282
references.citation: Vaccine. 2008 Sep 12;26 Suppl 4:D59-66
references.pmid: 19230162
references.citation: J Immunol. 1979 Jul;123(1):10-4
references.pmid: 448139
references.citation: Nat Immunol. 2004 Oct;5(10):981-6
references.pmid: 15454921
references.citation: J Exp Med. 2008 Jul 7;205(7):1621-34
references.pmid: 18591406
references.citation: Nat Immunol. 2010 May;11(5):404-10
references.pmid: 20383149
references.citation: J Virol. 2010 Dec;84(24):12564-75
references.pmid: 20943986
references.citation: Curr Opin Virol. 2012 Jun;2(3):287-93
references.pmid: 22542099
references.citation: Am J Respir Crit Care Med. 2008 Oct 1;178(7):667-72
references.pmid: 18565953
references.citation: J Immunol. 2012 Feb 1;188(3):1503-13
references.pmid: 22198948
references.citation: J Exp Med. 1997 Dec 15;186(12):2063-8
references.pmid: 9396777
references.citation: Virology. 2009 Sep 1;391(2):265-73
references.pmid: 19592063
references.citation: J Exp Med. 2010 Mar 15;207(3):521-34
references.pmid: 20212069
references.citation: N Engl J Med. 2011 May 12;364(19):1795-806
references.pmid: 21561345
references.citation: Thorax. 2010 Dec;65(12):1045-52
references.pmid: 20581410
references.citation: Nat Med. 2008 May;14(5):558-64
references.pmid: 18438414
references.citation: Med J Aust. 2006 Nov 20;185(S10):S44-7
references.pmid: 17115951
references.citation: J Leukoc Biol. 2007 Jan;81(1):1-5
references.pmid: 17032697
references.citation: Nat Immunol. 2010 Sep;11(9):785-97
references.pmid: 20720586
references.citation: J Immunol. 2006 Sep 1;177(5):2888-98
references.pmid: 16920924
references.citation: Nat Med. 2012 May;18(5):791-8
references.pmid: 22484808
references.citation: J Exp Med. 2007 Oct 29;204(11):2759-69
references.pmid: 17954569
references.citation: Proc Natl Acad Sci U S A. 2004 Jun 8;101(23):8670-5
references.pmid: 15163797
references.citation: Nat Immunol. 2011 Apr;12(4):304-11
references.pmid: 21378976
references.citation: Nat Immunol. 2009 Mar;10(3):266-72
references.pmid: 19158679
references.citation: PLoS Pathog. 2009 Oct;5(10):e1000604
references.pmid: 19798428
references.citation: J Exp Med. 2005 Mar 21;201(6):937-47
references.pmid: 15781584
references.citation: N Engl J Med. 1986 Jul 10;315(2):77-81
references.pmid: 3724802
references.citation: Am J Med. 2005 Mar;118(3):285-91
references.pmid: 15745727
references.citation: Crit Care. 2010;14(2):219
references.pmid: 20459593
references.citation: J Virol. 2008 Mar;82(6):2741-51
references.pmid: 18199656