Sustained IFN-I expression during established persistent viral infection: A “bad seed” for protective immunity

Viruses

Volumn 10, Issue 1, 2018, Pages

  Dagenais Lussier, Xavier ^a   Loucif, Hamza ^a   Murira, Armstrong ^a   Laulhé, Xavier ^a   Stäger, Simona ^a   Lamarre, Alain ^a   van Grevenynghe, Julien ^a  

^a INRS INSTITUT ARMAND FRAPPIER   (Canada)

Author keywords

Cell loss; Exhaustion; IFNR blockade; Immune activation inflammation; Immunosuppression; Persistent infection; Sustained IFN I expression

Indexed keywords

INTERFERON; PROGRAMMED DEATH 1 LIGAND 1; ALPHA BETA INTERFERON RECEPTOR; ANTIVIRUS AGENT;

DISEASE COURSE; DOWN REGULATION; IMMUNE RESPONSE; IMMUNOSUPPRESSIVE TREATMENT; LYMPHOCYTIC CHORIOMENINGITIS; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; NONHUMAN; PERSISTENT INFECTION; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; UPREGULATION; VIRUS INFECTION; ANIMAL; ANTAGONISTS AND INHIBITORS; BIOLOGICAL MODEL; CHRONIC DISEASE; DRUG EFFECT; GENETICS; HUMAN; IMMUNOLOGICAL TOLERANCE; IMMUNOLOGY; METABOLISM;

ANIMALS; ANTIVIRAL AGENTS; CHRONIC DISEASE; HUMANS; IMMUNE TOLERANCE; INTERFERON TYPE I; MODELS, IMMUNOLOGICAL; RECEPTOR, INTERFERON ALPHA-BETA; SIGNAL TRANSDUCTION; VIRUS DISEASES;

EID: 85040049456     PISSN: None     EISSN: 19994915     Source Type: Journal    
DOI: 10.3390/v10010012     Document Type: Review

References (75)

1. Acchioni, C.; Marsili, G.; Perrotti, E.; Remoli, A.L.; Sgarbanti, M.; Battistini, A. Type I IFN-A blunt spear in fighting HIV-1 infection. Cytokine Growth Factor Rev. 2015, 26, 143-158.
2. Borden, E.C.; Sen, G.C.; Uze, G.; Silverman, R.H.; Ransohoff, R.M.; Foster, G.R.; Stark, G.R. Interferons at age 50: Past, current and future impact on biomedicine. Nat. Rev. Drug Discov. 2007, 6, 975-990.
3. Snell, L.M.; McGaha, T.L.; Brooks, D.G. Type I interferon in chronic virus infection and cancer. Trends Immunol. 2017, 38, 542-557.
4. Teijaro, J.R. Type I interferons in viral control and immune regulation. Curr. Opin. Virol. 2016, 16, 31-40.
5. Gonzalez, S.A.; Keeffe, E.B. Chronic viral hepatitis: Epidemiology, molecular biology, and antiviral therapy. Front. Biosci. 2011, 16, 225-250.
6. Sandler, N.G.; Bosinger, S.E.; Estes, J.D.; Zhu, R.T.; Tharp, G.K.; Boritz, E.; Levin, D.; Wijeyesinghe, S.; Makamdop, K.N.; del Prete, G.Q.; et al. Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 2014, 511, 601-605.
7. Cha, L.; Berry, C.M.; Nolan, D.; Castley, A.; Fernandez, S.; French, M.A. Interferon-α, immune activation and immune dysfunction in treated HIV infection. Clin. Transl. Immunol. 2014, 3, e10.
8. Hardy, G.A.; Sieg, S.; Rodriguez, B.; Anthony, D.; Asaad, R.; Jiang, W.; Mudd, J.; Schacker, T.; Funderburg, N.T.; Pilch-Cooper, H.A.; et al. Interferon-α is the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers. PLoS ONE 2013, 8, e56527.
9. Said, E.A.; Dupuy, F.P.; Trautmann, L.; Zhang, Y.; Shi, Y.; El-Far, M.; Hill, B.J.; Noto, A.; Ancuta, P.; Peretz, Y.; et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nat. Med. 2010, 16, 452-459.
10. Trautmann, L.; Janbazian, L.; Chomont, N.; Said, E.A.; Gimmig, S.; Bessette, B.; Boulassel, M.R.; Delwart, E.; Sepulveda, H.; Balderas, R.S.; et al. Up regulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat. Med. 2006, 12, 1198-1202.
11. Trautmann, L.; Said, E.A.; Halwani, R.; Janbazian, L.; Chomont, N.; El-Far, M.; Breton, G.; Haddad, E.K.; Sekaly, R.P. Programmed death 1: A critical regulator of T-cell function and a strong target for immunotherapies for chronic viral infections. Curr. Opin. HIV AIDS 2007, 2, 219-227.
12. Van Grevenynghe, J.; Cubas, R.A.; DaFonseca, S.; Metcalf, T.; Tremblay, C.L.; Trautmann, L.; Sekaly, R.P.; Schatzle, J.; Haddad, E.K. Foxo3a: An integrator of immune dysfunction during HIV infection. Cytokine Growth Factor Rev. 2012, 23, 215-221.
13. Van Grevenynghe, J.; Cubas, R.A.; Noto, A.; DaFonseca, S.; He, Z.; Peretz, Y.; Filali-Mouhim, A.; Dupuy, F.P.; Procopio, F.A.; Chomont, N.; et al. Loss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis. J. Clin. Investig. 2011, 121, 3877-3888.
14. Van Grevenynghe, J.; Procopio, F.A.; He, Z.; Chomont, N.; Riou, C.; Zhang, Y.; Gimmig, S.; Boucher, G.; Wilkinson, P.; Shi, Y.; et al. Transcription factor Foxo3a controls the persistence of memory CD4(+) T cells during hiv infection. Nat. Med. 2008, 14, 266-274.
15. Beltra, J.C.; Decaluwe, H. Cytokines and persistent viral infections. Cytokine 2016, 82, 4-15.
16. Bolen, C.R.; Robek, M.D.; Brodsky, L.; Schulz, V.; Lim, J.K.; Taylor, M.W.; Kleinstein, S.H. The blood transcriptional signature of chronic hepatitis C virus is consistent with an ongoing interferon-mediated antiviral response. J. Interferon Cytokine Res. 2013, 33, 15-23.
17. Bosinger, S.E.; Utay, N.S. Type I interferon: Understanding its role in HIV pathogenesis and therapy. Curr. HIV/AIDS Rep. 2015, 12, 41-53.
18. Cheng, L.; Ma, J.; Li, J.; Li, D.; Li, G.; Li, F.; Zhang, Q.; Yu, H.; Yasui, F.; Ye, C.; et al. Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. J. Clin. Investig. 2017, 127, 269-279.
19. Cheng, L.; Yu, H.; Li, G.; Li, F.; Ma, J.; Li, J.; Chi, L.; Zhang, L.; Su, L. Type I interferons suppress viral replication but contribute to T cell depletion and dysfunction during chronic HIV-1 infection. JCI Insight 2017, 2, e94366.
20. Fernandez, S.; Tanaskovic, S.; Helbig, K.; Rajasuriar, R.; Kramski, M.; Murray, J.M.; Beard, M.; Purcell, D.; Lewin, S.R.; Price, P.; et al. CD4+ T-cell deficiency in HIV patients responding to antiretroviral therapy is associated with increased expression of interferon-stimulated genes in CD4+ T cells. J. Infect. Dis. 2011, 204, 1927-1935.
21. Guidotti, L.G.; Chisari, F.V. Immunobiology and pathogenesis of viral hepatitis. Annu. Rev. Pathol. 2006, 1, 23-61.
22. Hardy, G.A.; Sieg, S.F.; Rodriguez, B.; Jiang, W.; Asaad, R.; Lederman, M.M.; Harding, C.V. Desensitization to type I interferon in HIV-1 infection correlates with markers of immune activation and disease progression. Blood 2009, 113, 5497-5505.
23. Honke, N.; Shaabani, N.; Merches, K.; Gassa, A.; Kraft, A.; Ehrhardt, K.; Haussinger, D.; Lohning, M.; Dittmer, U.; Hengel, H.; et al. Immunoactivation induced by chronic viral infection inhibits viral replication and drives immunosuppression through sustained IFN-I responses. Eur. J. Immunol. 2016, 46, 372-380.
24. Marsili, G.; Remoli, A.L.; Sgarbanti, M.; Perrotti, E.; Fragale, A.; Battistini, A. HIV-1, interferon and the interferon regulatory factor system: An interplay between induction, antiviral responses and viral evasion. Cytokine Growth Factor Rev. 2012, 23, 255-270.
25. Su, A.I.; Pezacki, J.P.; Wodicka, L.; Brideau, A.D.; Supekova, L.; Thimme, R.; Wieland, S.; Bukh, J.; Purcell, R.H.; Schultz, P.G.; et al. Genomic analysis of the host response to hepatitis C virus infection. Proc. Natl. Acad. Sci. USA 2002, 99, 15669-15674.
26. Teijaro, J.R.; Ng, C.; Lee, A.M.; Sullivan, B.M.; Sheehan, K.C.; Welch, M.; Schreiber, R.D.; de la Torre, J.C.; Oldstone, M.B. Persistent LCMV infection is controlled by blockade of type I interferon signaling. Science 2013, 340, 207-211.
27. Wang, B.; Kang, W.; Zuo, J.; Kang, W.; Sun, Y. The significance of type-I interferons in the pathogenesis and therapy of human immunodeficiency virus 1 infection. Front. Immunol. 2017, 8, 1431.
28. Wilson, E.B.; Brooks, D.G. Decoding the complexity of type I interferon to treat persistent viral infections. Trends Microbiol. 2013, 21, 634-640.
29. Wilson, E.B.; Yamada, D.H.; Elsaesser, H.; Herskovitz, J.; Deng, J.; Cheng, G.; Aronow, B.J.; Karp, C.L.; Brooks, D.G. Blockade of chronic type I interferon signaling to control persistent LCMV infection. Science 2013, 340, 202-207.
30. Harris, L.D.; Tabb, B.; Sodora, D.L.; Paiardini, M.; Klatt, N.R.; Douek, D.C.; Silvestri, G.; Muller-Trutwin, M.; Vasile-Pandrea, I.; Apetrei, C.; et al. Down regulation of robust acute type I interferon responses distinguishes nonpathogenic simian immunodeficiency virus (SIV) infection of natural hosts from pathogenic SIV infection of rhesus macaques. J. Virol. 2010, 84, 7886-7891.
31. Jacquelin, B.; Mayau, V.; Targat, B.; Liovat, A.S.; Kunkel, D.; Petitjean, G.; Dillies, M.A.; Roques, P.; Butor, C.; Silvestri, G.; et al. Nonpathogenic SIV infection of african green monkeys induces a strong but rapidly controlled type I IFN response. J. Clin. Investig. 2009, 119, 3544-3555.
32. Mandl, J.N.; Barry, A.P.; Vanderford, T.H.; Kozyr, N.; Chavan, R.; Klucking, S.; Barrat, F.J.; Coffman, R.L.; Staprans, S.I.; Feinberg, M.B. Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections. Nat. Med. 2008, 14, 1077-1087.
33. Rotger, M.; Dalmau, J.; Rauch, A.; McLaren, P.; Bosinger, S.E.; Martinez, R.; Sandler, N.G.; Roque, A.; Liebner, J.; Battegay, M.; et al. Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. J. Clin. Investig. 2011, 121, 2391-2400.
34. Boasso, A.; Shearer, G.M. Chronic innate immune activation as a cause of HIV-1 immunopathogenesis. Clin. Immunol. 2008, 126, 235-242.
35. Sedaghat, A.R.; German, J.; Teslovich, T.M.; Cofrancesco, J., Jr.; Jie, C.C.; Talbot, C.C., Jr.; Siliciano, R.F. Chronic CD4+ T-cell activation and depletion in human immunodeficiency virus type 1 infection: Type I interferon-mediated disruption of T-cell dynamics. J. Virol. 2008, 82, 1870-1883.
36. Stylianou, E.; Aukrust, P.; Bendtzen, K.; Muller, F.; Froland, S.S. Interferons and interferon (IFN)-inducible protein 10 during highly active anti-retroviral therapy (HAART)-possible immunosuppressive role of IFN-alpha in HIV infection. Clin. Exp. Immunol. 2000, 119, 479-485.
37. Van Grevenynghe, J.; Halwani, R.; Chomont, N.; Ancuta, P.; Peretz, Y.; Tanel, A.; Procopio, F.A.; Shi, Y.; Said, E.A.; Haddad, E.K.; et al. Lymph node architecture collapse and consequent modulation of FOXO3a pathway on memory T- and B-cells during HIV infection. Semin. Immunol. 2008, 20, 196-203.
38. Zhen, A.; Rezek, V.; Youn, C.; Lam, B.; Chang, N.; Rick, J.; Carrillo, M.; Martin, H.; Kasparian, S.; Syed, P.; et al. Targeting type I interferon-mediated activation restores immune function in chronic HIV infection. J. Clin. Investig. 2017, 127, 260-268.
39. McBride, J.M.; Jiang, J.; Abbas, A.R.; Morimoto, A.; Li, J.; Maciuca, R.; Townsend, M.; Wallace, D.J.; Kennedy, W.P.; Drappa, J. Safety and pharmacodynamics of rontalizumab in patients with systemic lupus erythematosus: Results of a phase I, placebo-controlled, double-blind, dose-escalation study. Arthritis Rheum. 2012, 64, 3666-3676.
40. Wang, B.; Higgs, B.W.; Chang, L.; Vainshtein, I.; Liu, Z.; Streicher, K.; Liang, M.; White, W.I.; Yoo, S.; Richman, L.; et al. Pharmacogenomics and translational simulations to bridge indications for an anti-interferon-α receptor antibody. Clin. Pharmacol. Ther. 2013, 93, 483-492.
41. Wilson, E.B.; Brooks, D.G. Interfering with type I interferon: A novel approach to purge persistent viral infection. Cell Cycle 2013, 12, 2919-2920.
42. Herbeuval, J.P.; Nilsson, J.; Boasso, A.; Hardy, A.W.; Kruhlak, M.J.; Anderson, S.A.; Dolan, M.J.; Dy, M.; Andersson, J.; Shearer, G.M. Differential expression of IFN-α and TRAIL/DR5 in lymphoid tissue of progressor versus nonprogressor HIV-1-infected patients. Proc. Natl. Acad. Sci. USA 2006, 103, 7000-7005.
43. Lehmann, C.; Harper, J.M.; Taubert, D.; Hartmann, P.; Fatkenheuer, G.; Jung, N.; van Lunzen, J.; Stellbrink, H.J.; Gallo, R.C.; Romerio, F. Increased interferon α expression in circulating plasmacytoid dendritic cells of HIV-1-infected patients. J. Acquir. Immune Defic. Syndr. 2008, 48, 522-530.
44. Veenhuis, R.T.; Freeman, Z.T.; Korleski, J.; Cohen, L.K.; Massaccesi, G.; Tomasi, A.; Boesch, A.W.; Ackerman, M.E.; Margolick, J.B.; Blankson, J.N.; et al. HIV-antibody complexes enhance production of type I interferon by plasmacytoid dendritic cells. J. Clin. Investig. 2017, 127, 4352-4364.
45. Swiecki, M.; Wang, Y.; Vermi, W.; Gilfillan, S.; Schreiber, R.D.; Colonna, M. Type I interferon negatively controls plasmacytoid dendritic cell numbers in vivo. J. Exp. Med. 2011, 208, 2367-2374.
46. Boasso, A.; Hardy, A.W.; Landay, A.L.; Martinson, J.L.; Anderson, S.A.; Dolan, M.J.; Clerici, M.; Shearer, G.M. PDL-1 upregulation on monocytes and T cells by HIV via type I interferon: Restricted expression of type I interferon receptor by CCR5-expressing leukocytes. Clin. Immunol. 2008, 129, 132-144.
47. Sehgal, M.; Zeremski, M.; Talal, A.H.; Ginwala, R.; Elrod, E.; Grakoui, A.; Li, Q.G.; Philip, R.; Khan, Z.K.; Jain, P. IFN-alpha-induced downregulation of miR-221 in dendritic cells: Implications for HCV pathogenesis and treatment. J. Interferon Cytokine Res. 2015, 35, 698-709.
48. Cunningham, C.R.; Champhekar, A.; Tullius, M.V.; Dillon, B.J.; Zhen, A.; de la Fuente, J.R.; Herskovitz, J.; Elsaesser, H.; Snell, L.M.; Wilson, E.B.; et al. Type I and type II interferon coordinately regulate suppressive dendritic cell fate and function during viral persistence. PLoS Pathog. 2016, 12, e1005356.
49. Honke, N.; Shaabani, N.; Cadeddu, G.; Sorg, U.R.; Zhang, D.E.; Trilling, M.; Klingel, K.; Sauter, M.; Kandolf, R.; Gailus, N.; et al. Enforced viral replication activates adaptive immunity and is essential for the control of a cytopathic virus. Nat. Immunol. 2011, 13, 51-57.
50. Norris, B.A.; Uebelhoer, L.S.; Nakaya, H.I.; Price, A.A.; Grakoui, A.; Pulendran, B. Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity. Immunity 2013, 38, 309-321.
51. Taleb, K.; Auffray, C.; Villefroy, P.; Pereira, A.; Hosmalin, A.; Gaudry, M.; Le Bon, A. Chronic type I IFN is sufficient to promote immunosuppression through accumulation of myeloid-derived suppressor cells. J. Immunol. 2017, 198, 1156-1163.
52. Rempel, H.; Sun, B.; Calosing, C.; Pillai, S.K.; Pulliam, L. Interferon-α drives monocyte gene expression in chronic unsuppressed HIV-1 infection. AIDS 2010, 24, 1415-1423.
53. Herbeuval, J.P.; Grivel, J.C.; Boasso, A.; Hardy, A.W.; Chougnet, C.; Dolan, M.J.; Yagita, H.; Lifson, J.D.; Shearer, G.M. CD4+ T-cell death induced by infectious and noninfectious HIV-1: Role of type 1 interferon-dependent, TRAIL/DR5-mediated apoptosis. Blood 2005, 106, 3524-3531.
54. Kardava, L.; Moir, S.; Shah, N.; Wang, W.; Wilson, R.; Buckner, C.M.; Santich, B.H.; Kim, L.J.; Spurlin, E.E.; Nelson, A.K.; et al. Abnormal B cell memory subsets dominate HIV-specific responses in infected individuals. J. Clin. Investig. 2014, 124, 3252-3262.
55. Fallet, B.; Narr, K.; Ertuna, Y.I.; Remy, M.; Sommerstein, R.; Cornille, K.; Kreutzfeldt, M.; Page, N.; Zimmer, G.; Geier, F.; et al. Interferon-driven deletion of antiviral B cells at the onset of chronic infection. Sci. Immunol. 2016, 1.
56. Moir, S.; Fauci, A.S. Insights into B cells and HIV-specific B-cell responses in HIV-infected individuals. Immunol. Rev. 2013, 254, 207-224.
57. Moseman, E.A.; Wu, T.; de la Torre, J.C.; Schwartzberg, P.L.; McGavern, D.B. Type I interferon suppresses virus-specific B cell responses by modulating CD8+ T cell differentiation. Sci. Immunol. 2016, 1.
58. Sammicheli, S.; Kuka, M.; Di Lucia, P.; de Oya, N.J.; De Giovanni, M.; Fioravanti, J.; Cristofani, C.; Maganuco, C.G.; Fallet, B.; Ganzer, L.; et al. Inflammatory monocytes hinder antiviral B cell responses. Sci. Immunol. 2016, 1.
59. Herbeuval, J.P.; Hardy, A.W.; Boasso, A.; Anderson, S.A.; Dolan, M.J.; Dy, M.; Shearer, G.M. Regulation of tnf-related apoptosis-inducing ligand on primary CD4+ T cells by HIV-1: Role of type I IFN-producing plasmacytoid dendritic cells. Proc. Natl. Acad. Sci. USA 2005, 102, 13974-13979.
60. Cha, L.; de Jong, E.; French, M.A.; Fernandez, S. IFN-alpha exerts opposing effects on activation-induced and IL-7-induced proliferation of T cells that may impair homeostatic maintenance of CD4+ T cell numbers in treated HIV infection. J. Immunol. 2014, 193, 2178-2186.
61. Moir, S.; Fauci, A.S. B-cell responses to HIV infection. Immunol. Rev. 2017, 275, 33-48.
62. Noto, A.; Pantaleo, G. B-cell abnormalities and impact on antibody response in HIV infection. Curr. Opin. HIV AIDS 2017, 12, 203-208.
63. Daugan, M.; Murira, A.; Mindt, B.C.; Germain, A.; Tarrab, E.; Lapierre, P.; Fritz, J.H.; Lamarre, A. Type I interferon impairs specific antibody responses early during establishment of LCMV infection. Front. Immunol. 2016, 7, 564.
64. Aounallah, M.; Dagenais-Lussier, X.; El-Far, M.; Mehraj, V.; Jenabian, M.A.; Routy, J.P.; van Grevenynghe, J. Current topics in HIV pathogenesis, part 2: Inflammation drives a warburg-like effect on the metabolism of HIV-infected subjects. Cytokine Growth Factor Rev. 2016, 28, 1-10.
65. El-Far, M.; Halwani, R.; Said, E.; Trautmann, L.; Doroudchi, M.; Janbazian, L.; Fonseca, S.; van Grevenynghe, J.; Yassine-Diab, B.; Sekaly, R.P.; et al. T-cell exhaustion in HIV infection. Curr. HIV/AIDS Rep. 2008, 5, 13-19.
66. Fraietta, J.A.; Mueller, Y.M.; Yang, G.; Boesteanu, A.C.; Gracias, D.T.; Do, D.H.; Hope, J.L.; Kathuria, N.; McGettigan, S.E.; Lewis, M.G.; et al. Type I interferon upregulates bak and contributes to T cell loss during human immunodeficiency virus (HIV) infection. PLoS Pathog. 2013, 9, e1003658.
67. Le Saout, C.; Hasley, R.B.; Imamichi, H.; Tcheung, L.; Hu, Z.; Luckey, M.A.; Park, J.H.; Durum, S.K.; Smith, M.; Rupert, A.W.; et al. Chronic exposure to type-I IFN under lymphopenic conditions alters CD4 T cell homeostasis. PLoS Pathog. 2014, 10, e1003976.
68. Boasso, A.; Hardy, A.W.; Anderson, S.A.; Dolan, M.J.; Shearer, G.M. HIV-induced type I interferon and tryptophan catabolism drive T cell dysfunction despite phenotypic activation. PLoS ONE 2008, 3, e2961.
69. Zhang, Z.; Xu, X.; Lu, J.; Zhang, S.; Gu, L.; Fu, J.; Jin, L.; Li, H.; Zhao, M.; Zhang, J.; et al. B and T lymphocyte attenuator down-regulation by HIV-1 depends on type I interferon and contributes to T-cell hyperactivation. J. Infect. Dis. 2011, 203, 1668-1678.
70. Crawford, A.; Angelosanto, J.M.; Kao, C.; Doering, T.A.; Odorizzi, P.M.; Barnett, B.E.; Wherry, E.J. Molecular and transcriptional basis of CD4(+) T cell dysfunction during chronic infection. Immunity 2014, 40, 289-302.
71. Osokine, I.; Snell, L.M.; Cunningham, C.R.; Yamada, D.H.; Wilson, E.B.; Elsaesser, H.J.; de la Torre, J.C.; Brooks, D. Type I interferon suppresses de novo virus-specific CD4 Th1 immunity during an established persistent viral infection. Proc. Natl. Acad. Sci. USA 2014, 111, 7409-7414.
72. Che, J.W.; Kraft, A.R.; Selin, L.K.; Welsh, R.M. Regulatory T cells resist virus infection-induced apoptosis. J. Virol. 2015, 89, 2112-2120.
73. Srivastava, S.; Koch, M.A.; Pepper, M.; Campbell, D.J. Type I interferons directly inhibit regulatory T cells to allow optimal antiviral T cell responses during acute LCMV infection. J. Exp. Med. 2014, 211, 961-974.
74. Penaloza-MacMaster, P.; Kamphorst, A.O.; Wieland, A.; Araki, K.; Iyer, S.S.; West, E.E.; O’Mara, L.; Yang, S.; Konieczny, B.T.; Sharpe, A.H.; et al. Interplay between regulatory T cells and PD-1 in modulating T cell exhaustion and viral control during chronic LCMV infection. J. Exp. Med. 2014, 211, 1905-1918.
75. Wang, Y.; Swiecki, M.; Cella, M.; Alber, G.; Schreiber, R.D.; Gilfillan, S.; Colonna, M. Timing and magnitude of type I interferon responses by distinct sensors impact CD8 T cell exhaustion and chronic viral infection. Cell Host Microbe 2012, 11, 631-642.