title: Race between retroviral spread and CD4+ T-cell response determines the outcome of acute Friend virus infection.
abstract: Retroviruses can establish persistent infection despite induction of a multipartite antiviral immune response. Whether collective failure of all parts of the immune response or selective deficiency in one crucial part underlies the inability of the host to clear retroviral infections is currently uncertain. We examine here the contribution of virus-specific CD4(+) T cells in resistance against Friend virus (FV) infection in the murine host. We show that the magnitude and duration of the FV-specific CD4(+) T-cell response is directly proportional to resistance against acute FV infection and subsequent disease. Notably, significant protection against FV-induced disease is afforded by FV-specific CD4(+) T cells in the absence of a virus-specific CD8(+) T-cell or B-cell response. Enhanced spread of FV infection in hosts with increased genetic susceptibility or coinfection with Lactate dehydrogenase-elevating virus (LDV) causes a proportional increase in the number of FV-specific CD4(+) T cells required to control FV-induced disease. Furthermore, ultimate failure of FV/LDV coinfected hosts to control FV-induced disease is accompanied by accelerated contraction of the FV-specific CD4(+) T-cell response. Conversely, an increased frequency or continuous supply of FV-specific CD4(+) T cells is both necessary and sufficient to effectively contain acute infection and prevent disease, even in the presence of coinfection. Thus, these results suggest that FV-specific CD4(+) T cells provide significant direct protection against acute FV infection, the extent of which critically depends on the ratio of FV-infected cells to FV-specific CD4(+) T cells.
authors.affiliation: Division of Immunoregulation, MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Pike
authors.forename: Andrew
authors.initials: A
authors.lastname: Filby
authors.forename: Mickaël J-Y
authors.initials: MJ
authors.lastname: Ploquin
authors.forename: Urszula
authors.initials: U
authors.lastname: Eksmond
authors.forename: Rute
authors.initials: R
authors.lastname: Marques
authors.forename: Inês
authors.initials: I
authors.lastname: Antunes
authors.forename: Kim
authors.initials: K
authors.lastname: Hasenkrug
authors.forename: George
authors.initials: G
authors.lastname: Kassiotis
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D005622:Friend murine leukemia virus / Q000276:immunology*; D007772:Lactate dehydrogenase-elevating virus / Q000276:immunology; D007942:Leukemia, Experimental / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D017471:Receptors, Interferon / Q000235:genetics / Q000276:immunology; D012192:Retroviridae Infections / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*; D000096743:Interferon gamma Receptor
chemical_list: D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor
references.citation: J Exp Med. 1981 Sep 1;154(3):952-63
references.pmid: 6974221
references.citation: Blood. 2000 Dec 1;96(12):3675-80
references.pmid: 11090047
references.citation: Eur J Immunol. 1998 Jan;28(1):390-400
references.pmid: 9485218
references.citation: J Virol. 1992 Jun;66(6):3271-7
references.pmid: 1374804
references.citation: J Immunol. 2008 Dec 15;181(12):8568-75
references.pmid: 19050276
references.citation: J Virol. 2008 Dec;82(24):12432-40
references.pmid: 18842712
references.citation: J Virol. 2004 Jul;78(13):6827-35
references.pmid: 15194758
references.citation: Curr Top Microbiol Immunol. 1989;148:1-42
references.pmid: 2684547
references.citation: J Virol. 2007 Nov;81(22):12535-42
references.pmid: 17652379
references.citation: J Virol. 2005 Aug;79(16):10514-27
references.pmid: 16051844
references.citation: J Virol. 1998 Aug;72(8):6559-64
references.pmid: 9658100
references.citation: J Virol. 2001 Apr;75(7):3152-63
references.pmid: 11238842
references.citation: Science. 1993 Sep 10;261(5127):1448-51
references.pmid: 8367726
references.citation: Immunity. 2000 Jun;12(6):677-86
references.pmid: 10894167
references.citation: J Exp Med. 1998 Mar 2;187(5):693-702
references.pmid: 9480979
references.citation: Trends Immunol. 2006 Jun;27(6):274-81
references.pmid: 16679064
references.citation: Nat Immunol. 2005 Sep;6(9):873-9
references.pmid: 16116467
references.citation: Eur J Immunol. 1995 Apr;25(4):1109-12
references.pmid: 7737281
references.citation: Cell. 1991 Sep 6;66(5):1051-66
references.pmid: 1909605
references.citation: Trends Immunol. 2006 Mar;27(3):119-24
references.pmid: 16458605
references.citation: Nature. 2002 May 2;417(6884):95-8
references.pmid: 11986671
references.citation: Immunity. 1998 Oct;9(4):449-57
references.pmid: 9806631
references.citation: J Virol. 2000 Aug;74(16):7422-30
references.pmid: 10906195
references.citation: Eur J Immunol. 1994 Sep;24(9):2213-8
references.pmid: 7916297
references.citation: Blood. 2007 Jun 15;109(12):5346-54
references.pmid: 17327412
references.citation: Int Immunol. 2006 Jan;18(1):183-98
references.pmid: 16352628
references.citation: Vaccine. 2008 Jun 6;26(24):2981-96
references.pmid: 18255203
references.citation: Blood. 2007 Dec 1;110(12):3949-58
references.pmid: 17699743
references.citation: J Immunol. 2006 Dec 15;177(12):8851-9
references.pmid: 17142788
references.citation: Annu Rev Immunol. 1999;17:625-56
references.pmid: 10358770
references.citation: Nat Med. 1999 Feb;5(2):189-93
references.pmid: 9930867
references.citation: Science. 2008 Sep 5;321(5894):1343-6
references.pmid: 18772436
references.citation: J Immunol. 2002 Aug 1;169(3):1593-603
references.pmid: 12133989
references.citation: J Exp Med. 1985 May 1;161(5):1122-34
references.pmid: 3921652
references.citation: Curr Opin Immunol. 2006 Aug;18(4):399-405
references.pmid: 16753288
references.citation: Virology. 1983 May;127(1):134-48
references.pmid: 6305011
references.citation: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8633-8
references.pmid: 10411927
references.citation: Infect Immun. 2007 Apr;75(4):1545-55
references.pmid: 17283094
references.citation: J Natl Cancer Inst. 1978 Jan;60(1):239-42
references.pmid: 564410
references.citation: Curr Opin Immunol. 2000 Aug;12(4):381-6
references.pmid: 10899031
references.citation: J Virol. 2008 Jan;82(1):408-18
references.pmid: 17959678
references.citation: Immunity. 2008 Nov 14;29(5):782-94
references.pmid: 19006695
references.citation: J Exp Med. 2006 Dec 25;203(13):2865-77
references.pmid: 17158960
references.citation: J Virol. 1999 Aug;73(8):6468-73
references.pmid: 10400741
references.citation: J Immunol. 2008 Sep 1;181(5):3432-40
references.pmid: 18714015
references.citation: J Immunol. 1995 Jul 15;155(2):748-58
references.pmid: 7541823
references.citation: Science. 1997 Nov 21;278(5342):1447-50
references.pmid: 9367954
references.citation: J Virol. 2008 Oct;82(19):9678-88
references.pmid: 18667492
references.citation: Nat Med. 2006 Mar;12(3):289-95
references.pmid: 16520776
references.citation: Science. 1993 Mar 19;259(5102):1742-5
references.pmid: 8456301
references.citation: J Immunol. 1979 Oct;123(4):1822-8
references.pmid: 314476
references.citation: Nat Immunol. 2004 Sep;5(9):934-42
references.pmid: 15300247
references.citation: J Virol. 2001 Jan;75(1):52-60
references.pmid: 11119573
references.citation: Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):13026-31
references.pmid: 15326293
references.citation: J Immunol. 2002 Sep 15;169(6):3191-9
references.pmid: 12218137
references.citation: J Immunol. 2006 Sep 1;177(5):2888-98
references.pmid: 16920924
references.citation: Nature. 1995 May 11;375(6527):148-51
references.pmid: 7753171
references.citation: J Exp Med. 1995 Dec 1;182(6):1727-37
references.pmid: 7500017
references.citation: Rev Sci Tech. 1998 Apr;17(1):269-77
references.pmid: 9638816
references.citation: Proc Natl Acad Sci U S A. 1997 Jul 22;94(15):7811-6
references.pmid: 9223268
references.citation: J Immunol. 2005 Jan 15;174(2):614-8
references.pmid: 15634878
references.citation: Immunity. 1996 Apr;4(4):337-47
references.pmid: 8612128