NK cells improve control of friend virus infection in mice persistently infected with murine cytomegalovirus

Retrovirology

Anke RM Kraft¹  Ulf Dittmer²  Kathrin Gibbert²  Janine Duppach²  Tatjana Schwarz²  Jing Peng²  Sandra Francois² 

[1] Current address: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany;Institute for Virology of the University Hospital in Essen, University of Duisburg-Essen, Essen, Germany

关键词: CMV;    HIV;    NK cells;    Friend virus;    mCMV;    Heterologous immunity;    Superinfection;   

Others  :  1209119
DOI  :  10.1186/1742-4690-10-58

 received in 2013-01-02, accepted in 2013-05-19,  发布年份 2013

【 摘 要 】

Background

Co-infection of HIV patients with cytomegalovirus (CMV) is associated with enhanced AIDS progression and CMV end-organ diseases. On the other hand, persistent CMV infection has recently been shown to decrease tumor relapse and protect against lethal bacterial infection. The influence of persistent CMV on the outcome of an acute retroviral superinfection is still unknown.

Results

Here we show that a persistent murine CMV (mCMV) infection surprisingly confers higher resistance to a primary Friend retrovirus infection (FV) of mice. Decreased FV titers and augmented FV-specific CD8 T-cell responses were found in mCMV infected mice during primary FV superinfection. NK cells produced higher amounts of IFNgamma after FV infection of persistently mCMV infected mice suggesting that these cells were involved in the ‘protective’ effect. Depletion of NK1.1⁺ cells or neutralization of IFNgamma during FV superinfection abrogated the mCMV-mediated effect.

Conclusion

Our data demonstrate for the first time that a persistent CMV infection induces long-lasting NK cell responses that can enhance immunity to primary retroviral infections. To our knowledge, studies investigating primary HIV infection have not analyzed the role of the CMV seropositivity in these patients. Our observations suggest that NK cells in CMV seropositive individuals might contribute to the control of primary HIV infection.

【 授权许可】

   
2013 Francois et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Mori Y, Yamanishi K: HHV-6A, 6B, and 7: pathogenesis, host response, and clinical disease. In Human Herpesviruses: Biology, Therapy, and Immunoprophylaxis. Edited by Arvin A, Campadelli-Fiume G, Mocarski E, Moore PS, Roizman B, Whitley R, Yamanishi K. Cambridge: Cambridge University Press; 2007. Chapter 46
• [2]Bronke C, Palmer NM, Jansen CA, Westerlaken GH, Polstra AM, Reiss P, Bakker M, Miedema F, Tesselaar K, van Baarle D: Dynamics of cytomegalovirus (CMV)-specific T cells in HIV-1-infected individuals progressing to AIDS with CMV end-organ disease. J Infect Dis 2005, 191:873-880.
• [3]Bronke C, Westerlaken GH, Miedema F, Tesselaar K, van Baarle D: Progression to CMV end-organ disease in HIV-1-infected individuals despite abundance of highly differentiated CMV-specific CD8+ T-cells. Immunol Lett 2005, 97:215-224.
• [4]Sison RF, Holland GN, MacArthur LJ, Wheeler NC, Gottlieb MS: Cytomegalovirus retinopathy as the initial manifestation of the acquired immunodeficiency syndrome. Am J Ophthalmol 1991, 112:243-249.
• [5]Erice A, Tierney C, Hirsch M, Caliendo AM, Weinberg A, Kendall MA, Polsky B: Cytomegalovirus (CMV) and human immunodeficiency virus (HIV) burden, CMV end-organ disease, and survival in subjects with advanced HIV infection (AIDS clinical trials group protocol 360). Clin Infect Dis 2003, 37:567-578.
• [6]Guardia-Silva AC, Stucchi RS, Sampaio AM, Milan A, Costa SC, Boin IF: Detection of cytomegalovirus and human herpesvirus-6 DNA in liver biopsy specimens and their correlation with rejection after liver transplantation. Transplant Proc 2012, 44:2441-2444.
• [7]van der Bij W, Speich R: Management of cytomegalovirus infection and disease after solid-organ transplantation. Clin Infect Dis 2001, 33(Suppl 1):S32-S37.
• [8]Lerner CW, Tapper ML: Opportunistic infection complicating acquired immune deficiency syndrome. Clinical features of 25 cases. Medicine (Baltimore) 1984, 63:155-164.
• [9]Elmaagacli AH, Steckel NK, Koldehoff M, Hegerfeldt Y, Trenschel R, Ditschkowski M, Christoph S, Gromke T, Kordelas L, Ottinger HD, et al.: Early human cytomegalovirus replication after transplantation is associated with a decreased relapse risk: evidence for a putative virus-versus-leukemia effect in acute myeloid leukemia patients. Blood 2011, 118:1402-1412.
• [10]Barton ES, White DW, Cathelyn JS, Brett-McClellan KA, Engle M, Diamond MS, Miller VL, Virgin HWT: Herpesvirus latency confers symbiotic protection from bacterial infection. Nature 2007, 447:326-329.
• [11]Krmpotic A, Bubic I, Polic B, Lucin P, Jonjic S: Pathogenesis of murine cytomegalovirus infection. Microbes Infect 2003, 5:1263-1277.
• [12]Reddehase MJ, Simon CO, Seckert CK, Lemmermann N, Grzimek NK: Murine model of cytomegalovirus latency and reactivation. Curr Top Microbiol Immunol 2008, 325:315-331.
• [13]Lopez-Verges S, Milush JM, Schwartz BS, Pando MJ, Jarjoura J, York VA, Houchins JP, Miller S, Kang SM, Norris PJ, et al.: Expansion of a unique CD57(+)NKG2Chi natural killer cell subset during acute human cytomegalovirus infection. Proc Natl Acad Sci U S A 2011, 108:14725-14732.
• [14]Sun JC, Lopez-Verges S, Kim CC, DeRisi JL, Lanier LL: NK cells and immune “memory”. J Immunol 2011, 186:1891-1897.
• [15]Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL: Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 2002, 296:1323-1326.
• [16]Smith HR, Heusel JW, Mehta IK, Kim S, Dorner BG, Naidenko OV, Iizuka K, Furukawa H, Beckman DL, Pingel JT, et al.: Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci USA 2002, 99:8826-8831.
• [17]Kabat D: Molecular biology of friend viral erythroleukemia. Curr Top Microbiol Immunol 1989, 148:1-42.
• [18]Chesebro B, Wehrly K, Stimpfling J: Host genetic control of recovery from friend leukemia virus-induced splenomegaly: mapping of a gene within the major histocompatability complex. J Exp Med 1974, 140:1457-1467.
• [19]Zelinskyy G, Balkow S, Schimmer S, Werner T, Simon MM, Dittmer U: The level of friend retrovirus replication determines the cytolytic pathway of CD8+ T-cell-mediated pathogen control. J Virol 2007, 81:11881-11890.
• [20]Gerlach N, Schimmer S, Weiss S, Kalinke U, Dittmer U: Effects of type I interferons on friend retrovirus infection. J Virol 2006, 80:3438-3444.
• [21]Hasenkrug KJ, Brooks DM, Dittmer U: Critical role for CD4(+) T cells in controlling retrovirus replication and spread in persistently infected mice. J Virol 1998, 72:6559-6564.
• [22]Sun JC, Lanier LL: NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat Rev Immunol 2011, 11:645-657.
• [23]Dokun AO, Kim S, Smith HR, Kang HS, Chu DT, Yokoyama WM: Specific and nonspecific NK cell activation during virus infection. Nat Immunol 2001, 2:951-956.
• [24]Stromnes IM, Dittmer U, Schumacher TN, Schepers K, Messer RJ, Evans LH, Peterson KE, Race B, Hasenkrug KJ: Temporal effects of gamma interferon deficiency on the course of friend retrovirus infection in mice. J Virol 2002, 76:2225-2232.
• [25]Blattman JN, Grayson JM, Wherry EJ, Kaech SM, Smith KA, Ahmed R: Therapeutic use of IL-2 to enhance antiviral T-cell responses in vivo. Nat Med 2003, 9:540-547.
• [26]Van Parijs L, Refaeli Y, Lord JD, Nelson BH, Abbas AK, Baltimore D: Uncoupling IL-2 signals that regulate T cell proliferation, survival, and Fas-mediated activation-induced cell death. Immunity 1999, 11:281-288.
• [27]Tough DF, Borrow P, Sprent J: Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 1996, 272:1947-1950.
• [28]McNally JM, Zarozinski CC, Lin MY, Brehm MA, Chen HD, Welsh RM: Attrition of bystander CD8 T cells during virus-induced T-cell and interferon responses. J Virol 2001, 75:5965-5976.
• [29]Whitmire JK, Tan JT, Whitton JL: Interferon-gamma acts directly on CD8+ T cells to increase their abundance during virus infection. J Exp Med 2005, 201:1053-1059.
• [30]Duley AK, Ploquin MJ, Eksmond U, Ammann CG, Messer RJ, Myers L, Hasenkrug KJ, Kassiotis G: Negative impact of IFN-gamma on early host immune responses to retroviral infection. J Immunol 2012, 189:2521-2529.
• [31]Fan Z, Yu P, Wang Y, Fu ML, Liu W, Sun Y, Fu YX: NK-cell activation by LIGHT triggers tumor-specific CD8+ T-cell immunity to reject established tumors. Blood 2006, 107:1342-1351.
• [32]Mekker A, Tchang VS, Haeberli L, Oxenius A, Trkola A, Karrer U: Immune senescence: relative contributions of age and cytomegalovirus infection. PLoS Pathog 2012, 8:e1002850.
• [33]Cicin-Sain L, Brien JD, Uhrlaub JL, Drabig A, Marandu TF, Nikolich-Zugich J: Cytomegalovirus infection impairs immune responses and accentuates T-cell pool changes observed in mice with aging. PLoS Pathog 2012, 8:e1002849.
• [34]Shrestha B, Gottlieb D, Diamond MS: Infection and injury of neurons by west nile encephalitis virus. J Virol 2003, 77:13203-13213.
• [35]Babic M, Krmpotic A, Jonjic S: All is fair in virus-host interactions: NK cells and cytomegalovirus. Trends Mol Med 2011, 17:677-685.
• [36]Mitrovic M, Arapovic J, Jordan S, Fodil-Cornu N, Ebert S, Vidal SM, Krmpotic A, Reddehase MJ, Jonjic S: The NK cell response to mouse cytomegalovirus infection affects the level and kinetics of the early CD8(+) T-cell response. J Virol 2012, 86:2165-2175.
• [37]Waggoner SN, Cornberg M, Selin LK, Welsh RM: Natural killer cells act as rheostats modulating antiviral T cells. Nature 2011, 481:394-398.
• [38]Lang PA, Lang KS, Xu HC, Grusdat M, Parish IA, Recher M, Elford AR, Dhanji S, Shaabani N, Tran CW, et al.: Natural killer cell activation enhances immune pathology and promotes chronic infection by limiting CD8+ T-cell immunity. Proc Natl Acad Sci U S A 2012, 109:1210-1215.
• [39]Ravet S, Scott-Algara D, Bonnet E, Tran HK, Tran T, Nguyen N, Truong LX, Theodorou I, Barre-Sinoussi F, Pancino G, Paul P: Distinctive NK-cell receptor repertoires sustain high-level constitutive NK-cell activation in HIV-exposed uninfected individuals. Blood 2007, 109:4296-4305.
• [40]Scott-Algara D, Truong LX, Versmisse P, David A, Luong TT, Nguyen NV, Theodorou I, Barre-Sinoussi F, Pancino G: Cutting edge: increased NK cell activity in HIV-1-exposed but uninfected Vietnamese intravascular drug users. J Immunol 2003, 171:5663-5667.
• [41]Bukowski JF, Woda BA, Habu S, Okumura K, Welsh RM: Natural killer cell depletion enhances virus synthesis and virus-induced hepatitis in vivo. J Immunol 1983, 131:1531-1538.
• [42]Robertson SJ, Ammann CG, Messer RJ, Carmody AB, Myers L, Dittmer U, Nair S, Gerlach N, Evans LH, Cafruny WA, Hasenkrug KJ: Suppression of acute anti-friend virus CD8+ T-cell responses by coinfection with lactate dehydrogenase-elevating virus. J Virol 2008, 82:408-418.
• [43]Dittmer U, Brooks DM, Hasenkrug KJ: Characterization of a live-attenuated retroviral vaccine demonstrates protection via immune mechanisms. J Virol 1998, 72:6554-6558.
• [44]Chen HD, Fraire AE, Joris I, Welsh RM, Selin LK: Specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung. Am J Pathol 2003, 163:1341-1355.
• [45]Chen W, Qin H, Chesebro B, Cheever MA: Identification of a gag-encoded cytotoxic T-lymphocyte epitope from FBL-3 leukemia shared by friend, moloney, and rauscher murine leukemia virus-induced tumors. J Virol 1996, 70:7773-7782.
• [46]Schepers K, Toebes M, Sotthewes G, Vyth-Dreese FA, Dellemijn TA, Melief CJ, Ossendorp F, Schumacher TN: Differential kinetics of antigen-specific CD4+ and CD8+ T cell responses in the regression of retrovirus-induced sarcomas. J Immunol 2002, 169:3191-3199.
• [47]Zelinskyy G, Dietze KK, Husecken YP, Schimmer S, Nair S, Werner T, Gibbert K, Kershaw O, Gruber AD, Sparwasser T, Dittmer U: The regulatory T-cell response during acute retroviral infection is locally defined and controls the magnitude and duration of the virus-specific cytotoxic T-cell response. Blood 2009, 114:3199-3207.
• [48]Gibbert K, Joedicke JJ, Meryk A, Trilling M, Francois S, Duppach J, Kraft A, Lang KS, Dittmer U: Interferon-alpha subtype 11 activates NK cells and enables control of retroviral infection. PLoS Pathog 2012, 8:e1002868.