Activation of the innate immune response by endogenous retroviruses

Journal of General Virology

Volumn 96, Issue , 2015, Pages 1207-1218

  Hurst, Tara P ^a   Magiorkinis, Gkikas ^a  

^a UNIVERSITY OF OXFORD   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

COMPLEMENTARY DNA; GAG PROTEIN; INTERFERON REGULATORY FACTOR 3; INTERFERON REGULATORY FACTOR 7; INTERLEUKIN 18; INTERLEUKIN 1BETA; INTERLEUKIN 6; PATTERN RECOGNITION RECEPTOR; PROTEIN; RETINOIC ACID INDUCIBLE PROTEIN I; TOLL LIKE RECEPTOR 4; TOLL LIKE RECEPTOR 7; TOLL LIKE RECEPTOR 9; TREX1 PROTEIN; TUMOR NECROSIS FACTOR ALPHA; UNCLASSIFIED DRUG; VIRUS RNA; VIRUS PROTEIN;

DENDRITIC CELL; ENDOGENOUS RETROVIRUS; ENVELOPE GENE; HUMAN; INNATE IMMUNITY; NONHUMAN; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; ANIMAL; GENE EXPRESSION; GENETIC TRANSCRIPTION; IMMUNOLOGY; METABOLISM; MOUSE;

MUS;

ANIMALS; ENDOGENOUS RETROVIRUSES; GENE EXPRESSION; HUMANS; IMMUNITY, INNATE; MICE; RECEPTORS, PATTERN RECOGNITION; RNA, VIRAL; TRANSCRIPTION, GENETIC; VIRAL PROTEINS;

EID: 84937604420     PISSN: 00221317     EISSN: 14652099     Source Type: Journal    
DOI: 10.1099/vir.0.000017     Document Type: Review

References (95)

1. Ablasser, A., Hemmerling, I., Schmid-Burgk, J. L., Behrendt, R., Roers, A. & Hornung, V. (2014). TREX1 deficiency triggers cellautonomous immunity in a cGAS-dependent manner. J Immunol 192, 5993-5997.
2. Akers, J. C., Gonda, D., Kim, R., Carter, B. S. & Chen, C. C. (2013). Biogenesis of extracellular vesicles (EV): exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies. J Neurooncol 113, 1-11.
3. Ariza, M.-E. & Williams, M. V. (2011). A human endogenous retrovirus K dUTPase triggers a TH1, TH17 cytokine response: does it have a role in psoriasis? J Invest Dermatol 131, 2419-2427.
4. Aswad, A. & Katzourakis, A. (2012). Paleovirology and virally derived immunity. Trends Ecol Evol 27, 627-636.
5. Bannert, N. & Kurth, R. (2006). The evolutionary dynamics of human endogenous retroviral families. Annu Rev Genomics Hum Genet 7, 149-173.
6. Barrat, F. J., Meeker, T., Gregorio, J., Chan, J. H., Uematsu, S., Akira, S., Chang, B., Duramad, O. & Coffman, R. L. (2005). Nucleic acids of mammalian origin can act as endogenous ligands for Toll-like receptors and may promote systemic lupus erythematosus. J Exp Med 202, 1131-1139.
7. Baudino, L., Yoshinobu, K., Dunand-Sauthier, I., Evans, L. H. & Izui, S. (2010). TLR-mediated up-regulation of serum retroviral gp70 is controlled by the Sgp loci of lupus-prone mice. J Autoimmun 35, 153-159.
8. Beck-Engeser, G. B., Eilat, D. & Wabl, M. (2011). An autoimmune disease prevented by anti-retroviral drugs. Retrovirology 8, 91.
9. Berg, R. K., Melchjorsen, J., Rintahaka, J., Diget, E., Søby, S., Horan, K. A., Gorelick, R. J., Matikainen, S., Larsen, C. S. & other authors (2012). Genomic HIV RNA induces innate immune responses through RIG-I-dependent sensing of secondary-structured RNA. PLoS ONE 7, e29291.
10. Best, S., Le Tissier, P., Towers, G. & Stoye, J. P. (1996). Positional cloning of the mouse retrovirus restriction gene Fv1. Nature 382, 826-829.
11. Bieda, K., Hoffmann, A. & Boller, K. (2001). Phenotypic heterogeneity of human endogenous retrovirus particles produced by teratocarcinoma cell lines. J Gen Virol 82, 591-596.
12. Bonner, T. I., O'Connell, C. & Cohen, M. (1982). Cloned endogenous retroviral sequences from human DNA. Proc Natl Acad Sci U S A 79, 4709-4713.
13. Browne, E. P. (2011). Toll-like receptor 7 controls the anti-retroviral germinal center response. PLoS Pathog 7, e1002293.
14. Browne, E. P. (2013). Toll-like receptor 7 inhibits early acute retroviral infection through rapid lymphocyte responses. J Virol 87, 7357-7366.
15. Childs, K. S., Randall, R. E. & Goodbourn, S. (2013). LGP2 plays a critical role in sensitizing mda-5 to activation by double-stranded RNA. PLoS ONE 8, e64202.
16. Coffin, J. M. (1979). Structure, replication, and recombination of retrovirus genomes: some unifying hypotheses. J Gen Virol 42, 1-26.
17. Cohen, M., Kato, N. & Larsson, E. (1988). ERV3 human endogenous provirus mRNAs are expressed in normal and malignant tissues and cells, but not in choriocarcinoma tumor cells. J Cell Biochem 36, 121-128.
18. de Parseval, N., Lazar, V., Casella, J.-F., Benit, L. & Heidmann, T. (2003). Survey of human genes of retroviral origin: identification and transcriptome of the genes with coding capacity for complete envelope proteins. J Virol 77, 10414-10422.
19. Denner, J. (2014). The transmembrane proteins contribute to immunodeficiencies induced by HIV-1 and other retroviruses. AIDS 28, 1081-1090.
20. Dewannieux, M., Harper, F., Richaud, A., Letzelter, C., Ribet, D., Pierron, G. & Heidmann, T. (2006). Identification of an infectious progenitor for the multiple-copy HERV-K human endogenous retroelements. Genome Res 16, 1548-1556.
21. Dupressoir, A., Lavialle, C. & Heidmann, T. (2012). From ancestral infectious retroviruses to bona fide cellular genes: role of the captured syncytins in placentation. Placenta 33, 663-671.
22. Eckard, S. C., Rice, G. I., Fabre, A., Badens, C., Gray, E. E., Hartley, J. L., Crow, Y. J. & Stetson, D. B. (2014). The SKIV2L RNA exosome limits activation of the RIG-I-like receptors. Nat Immunol 15, 839-845.
23. Esnault, C., Heidmann, O., Delebecque, F., Dewannieux, M., Ribet, D., Hance, A. J., Heidmann, T. & Schwartz, O. (2005). APOBEC3G cytidine deaminase inhibits retrotransposition of endogenous retroviruses. Nature 433, 430-433.
24. Esnault, C., Millet, J., Schwartz, O. & Heidmann, T. (2006). Dual inhibitory effects of APOBEC family proteins on retrotransposition of mammalian endogenous retroviruses. Nucleic Acids Res 34, 1522-1531.
25. Gall, A., Treuting, P., Elkon, K. B., Loo, Y.-M., Gale, M., Jr, Barber, G. N. & Stetson, D. B. (2012). Autoimmunity initiates in nonhematopoietic cells and progresses via lymphocytes in an interferon-dependent autoimmune disease. Immunity 36, 120-131.
26. Gao, D., Wu, J., Wu, Y.-T., Du, F., Aroh, C., Yan, N., Sun, L. & Chen, Z. J. (2013). Cyclic GMP-AMP synthase is an innate immune sensor of HIV and other retroviruses. Science 341, 903-906.
27. Gürtler, C. & Bowie, A. G. (2013). Innate immune detection of microbial nucleic acids. Trends Microbiol 21, 413-420.
28. Harzmann, R., Löwer, J., Löwer, R., Bichler, K. H. & Kurth, R. (1982). Synthesis of retrovirus-like particles in testicular teratocarcinomas. J Urol 128, 1055-1059.
29. Hiscott, J. (2007). Triggering the innate antiviral response through IRF-3 activation. J Biol Chem 282, 15325-15329.
30. Hornung, V., Ablasser, A., Charrel-Dennis, M., Bauernfeind, F., Horvath, G., Caffrey, D. R., Latz, E. & Fitzgerald, K. A. (2009). AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458, 514-518.
31. Jakobsen, M. R., Bak, R. O., Andersen, A., Berg, R. K., Jensen, S. B., Jin, T., Laustsen, A., Hansen, K., Ostergaard, L. & other authors (2013). IFI16 senses DNA forms of the lentiviral replication cycle and controls HIV-1 replication. Proc Natl Acad Sci U S A 110, E4571-E4580.
32. Johnston, J. B., Silva, C., Holden, J., Warren, K. G., Clark, A. W. & Power, C. (2001). Monocyte activation and differentiation augment human endogenous retrovirus expression: implications for inflammatory brain diseases. Ann Neurol 50, 434-442.
33. Kaiser, S. M., Malik, H. S. & Emerman, M. (2007). Restriction of an extinct retrovirus by the human TRIM5α antiviral protein. Science 316, 1756-1758.
34. Kalter, S. S., Helmke, R. J., Panigel, M., Heberling, R. L., Felsburg, P. J. & Axelrod, L. R. (1973). Observations of apparent C-type particles in baboon (Papio cynocephalus) placentas. Science 179, 1332-1333.
35. Kassiotis, G. (2014). Endogenous retroviruses and the development of cancer. J Immunol 192, 1343-1349.
36. Kato, N., Pfeifer-Ohlsson, S., Kato, M., Larsson, E., Rydnert, J., Ohlsson, R. & Cohen, M. (1987). Tissue-specific expression of human provirus ERV3 mRNA in human placenta: two of the three ERV3 mRNAs contain human cellular sequences. J Virol 61, 2182-2191.
37. Kato, H., Takeuchi, O., Mikamo-Satoh, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T. S., Fujita, T. & Akira, S. (2008). Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J Exp Med 205, 1601-1610.
38. Katzourakis, A. & Tristem, M. (2005). Phylogeny of human endogenous and exogenous retroviruses. In Retroviruses and Primate Genome Evolution, pp. 186-203. Edited by E. Sverdlov. Austin, TX: Landes Bioscience.
39. Kawai, T. & Akira, S. (2009). The roles of TLRs, RLRs and NLRs in pathogen recognition. Int Immunol 21, 317-337.
40. Koh, Y. T., Scatizzi, J. C., Gahan, J. D., Lawson, B. R., Baccala, R., Pollard, K. M., Beutler, B. A., Theofilopoulos, A. N. & Kono, D. H. (2013). Role of nucleic acid-sensing TLRs in diverse autoantibody specificities and anti-nuclear antibody-producing B cells. J Immunol 190, 4982-4990.
41. Lander, E. S., Linton, L. M., Birren, B., Nusbaum, C., Zody, M. C., Baldwin, J., Devon, K., Dewar, K., Doyle, M. & other authors (2001). Initial sequencing and analysis of the human genome. Nature 409, 860-921.
42. Lavie, L., Kitova, M., Maldener, E., Meese, E. & Mayer, J. (2005). CpG methylation directly regulates transcriptional activity of the human endogenous retrovirus family HERV-K(HML-2). J Virol 79, 876-883.
43. Lee, Y. N. & Bieniasz, P. D. (2007). Reconstitution of an infectious human endogenous retrovirus. PLoS Pathog 3, e10.
44. Lee, Y. N., Malim, M. H. & Bieniasz, P. D. (2008). Hypermutation of an ancient human retrovirus by APOBEC3G. J Virol 82, 8762-8770.
45. Lester, S. N. & Li, K. (2014). Toll-like receptors in antiviral innate immunity. J Mol Biol 426, 1246-1264.
46. Loo, Y.-M. & Gale, M., Jr (2011). Immune signaling by RIG-I-like receptors. Immunity 34, 680-692.
47. Lu, X., Sachs, F., Ramsay, L., Jacques, P.-É., Göke, J., Bourque, G. & Ng, H.-H. (2014). The retrovirus HERVH is a long noncoding RNA required for human embryonic stem cell identity. Nat Struct Mol Biol 21, 423-425.
48. Magiorkinis, G., Gifford, R. J., Katzourakis, A., De Ranter, J. & Belshaw, R. (2012). Env-less endogenous retroviruses are genomic superspreaders. Proc Natl Acad Sci U S A 109, 7385-7390.
49. Mameli, G., Astone, V., Khalili, K., Serra, C., Sawaya, B. E. & Dolei, A. (2007). Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines. Virology 362, 120-130.
50. Mangeney, M., de Parseval, N., Thomas, G. & Heidmann, T. (2001). The full-length envelope of an HERV-H human endogenous retrovirus has immunosuppressive properties. J Gen Virol 82, 2515-2518.
51. Mangeney, M., Renard, M., Schlecht-Louf, G., Bouallaga, I., Heidmann, O., Letzelter, C., Richaud, A., Ducos, B. & Heidmann, T. (2007). Placental syncytins: genetic disjunction between the fusogenic and immunosuppressive activity of retroviral envelope proteins. Proc Natl Acad Sci U S A 104, 20534-20539.
52. Manghera, M. & Douville, R. N. (2013). Endogenous retrovirus-K promoter: a landing strip for inflammatory transcription factors? Retrovirology 10, 16.
53. Marchi, E., Kanapin, A., Magiorkinis, G. & Belshaw, R. (2014). Unfixed endogenous retroviral insertions in the human population. J Virol 88, 9529-9537.
54. Medstrand, P., Lindeskog, M. & Blomberg, J. (1992). Expression of human endogenous retroviral sequences in peripheral blood mononuclear cells of healthy individuals. J Gen Virol 73, 2463-2466.
55. Michaud, H.-A., de Mulder, M., SenGupta, D., Deeks, S. G., Martin, J. N., Pilcher, C. D., Hecht, F. M., Sacha, J. B. & Nixon, D. F. (2014). Trans-activation, post-transcriptional maturation, and induction of antibodies to HERV-K (HML-2) envelope transmembrane protein in HIV-1 infection. Retrovirology 11, 10.
56. Morozov, V. A., Dao Thi, V. L. & Denner, J. (2013). The transmembrane protein of the human endogenous retrovirus-K (HERV-K) modulates cytokine release and gene expression. PLoS ONE 8, e70399.
57. Murphy, K. M. & Reiner, S. L. (2002). The lineage decisions of helper T cells. Nat Rev Immunol 2, 933-944.
58. Nazli, A., Kafka, J. K., Ferreira, V. H., Anipindi, V., Mueller, K., Osborne, B. J., Dizzell, S., Chauvin, S., Mian, M. F. & other authors (2013). HIV-1 gp120 induces TLR2-and TLR4-mediated innate immune activation in human female genital epithelium. J Immunol 191, 4246-4258.
59. O'Neill, L. A. J., Golenbock, D. & Bowie, A. G. (2013). The history of Toll-like receptors-redefining innate immunity. Nat Rev Immunol 13, 453-460.
60. Okumura, A., Pitha, P. M., Yoshimura, A. & Harty, R. N. (2010). Interaction between Ebola virus glycoprotein and host Toll-like receptor 4 leads to induction of proinflammatory cytokines and SOCS1. J Virol 84, 27-33.
61. Ono, M. (1986). Molecular cloning and long terminal repeat sequences of human endogenous retrovirus genes related to types A and B retrovirus genes. J Virol 58, 937-944.
62. Paludan, S. R. & Bowie, A. G. (2013). Immune sensing of DNA. Immunity 38, 870-880.
63. Patel, M. R., Emerman, M. & Malik, H. S. (2011). Paleovirology-ghosts and gifts of viruses past. Curr Opin Virol 1, 304-309.
64. Pertel, T., Hausmann, S., Morger, D., Züger, S., Guerra, J., Lascano, J., Reinhard, C., Santoni, F. A., Uchil, P. D. & other authors (2011). TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature 472, 361-365.
65. Rabson, A. B., Steele, P. E., Garon, C. F. & Martin, M. A. (1983). mRNA transcripts related to full-length endogenous retroviral DNA in human cells. Nature 306, 604-607.
66. Reiss, D., Zhang, Y. & Mager, D. L. (2007). Widely variable endogenous retroviral methylation levels in human placenta. Nucleic Acids Res 35, 4743-4754.
67. Repaske, R., Steele, P. E., O'Neill, R. R., Rabson, A. B. & Martin, M. A. (1985). Nucleotide sequence of a full-length human endogenous retroviral segment. J Virol 54, 764-772.
68. Rice, G. I., Forte, G. M. A., Szynkiewicz, M., Chase, D. S., Aeby, A., Abdel-Hamid, M. S., Ackroyd, S., Allcock, R., Bailey, K. M. & other authors (2013). Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol 12, 1159-1169.
69. Rice, G. I., del Toro Duany, Y., Jenkinson, E. M., Forte, G. M. A., Anderson, B. H., Ariaudo, G., Bader-Meunier, B., Baildam, E. M., Battini, R. & other authors (2014). Gain-of-function mutations in IFIH1 cause a spectrum of human disease phenotypes associated with upregulated type I interferon signaling. Nat Genet 46, 503-509.
70. Rigby, R. E., Webb, L. M., Mackenzie, K. J., Li, Y., Leitch, A., Reijns, M. A. M., Lundie, R. J., Revuelta, A., Davidson, D. J. & other authors (2014). RNA:DNA hybrids are a novel molecular pattern sensed by TLR9. EMBO J 33, 542-558.
71. Rolland, A., Jouvin-Marche, E., Saresella, M., Ferrante, P., Cavaretta, R., Créange, A., Marche, P. & Perron, H. (2005). Correlation between disease severity and in vitro cytokine production mediated by MSRV (multiple sclerosis associated retroviral element) envelope protein in patients with multiple sclerosis. J Neuroimmunol 160, 195-203.
72. Rolland, A., Jouvin-Marche, E., Viret, C., Faure, M., Perron, H. & Marche, P. N. (2006). The envelope protein of a human endogenous retrovirus-W family activates innate immunity through CD14/TLR4 and promotes Th1-like responses. J Immunol 176, 7636-7644.
73. Ryoo, J., Choi, J., Oh, C., Kim, S., Seo, M., Kim, S.-Y., Seo, D., Kim, J., White, T. E. & other authors (2014). The ribonuclease activity of SAMHD1 is required for HIV-1 restriction. Nat Med 20, 936-941.
74. Sanville, B., Dolan, M. A., Wollenberg, K., Yan, Y., Martin, C., Yeung, M. L., Strebel, K., Buckler-White, A. & Kozak, C. A. (2010). Adaptive evolution of Mus Apobec3 includes retroviral insertion and positive selection at two clusters of residues flanking the substrate groove. PLoS Pathog 6, e1000974.
75. Saresella, M., Rolland, A., Marventano, I., Cavarretta, R., Caputo, D., Marche, P., Perron, H. & Clerici, M. (2009). Multiple sclerosisassociated retroviral agent (MSRV)-stimulated cytokine production in patients with relapsing-remitting multiple sclerosis. Mult Scler 15, 443-447.
76. Schoggins, J. W., MacDuff, D. A., Imanaka, N., Gainey, M. D., Shrestha, B., Eitson, J. L., Mar, K. B., Richardson, R. B., Ratushny, A. V. & other authors (2014). Pan-viral specificity of IFN-induced genes reveals new roles for cGAS in innate immunity. Nature 505, 691-695.
77. +T-lymphocytes cannot be upregulated by interferons. Retrovirology 9, 105.
78. Stetson, D. B., Ko, J. S., Heidmann, T. & Medzhitov, R. (2008). Trex1 prevents cell-intrinsic initiation of autoimmunity. Cell 134, 587-598.
79. Sze, A., Olagnier, D., Lin, R., van Grevenynghe, J. & Hiscott, J. (2013). SAMHD1 host restriction factor: a link with innate immune sensing of retrovirus infection. J Mol Biol 425, 4981-4994.
80. Szondy, Z., Garabuczi, E., Joós, G., Tsay, G. J. & Sarang, Z. (2014). Impaired clearance of apoptotic cells in chronic inflammatory diseases: therapeutic implications. Front Immunol 5, 354.
81. Takaoka, A., Wang, Z., Choi, M. K., Yanai, H., Negishi, H., Ban, T., Lu, Y., Miyagishi, M., Kodama, T. & other authors (2007). DAI (DLM-1/ ZBP1) is a cytosolic DNA sensor and an activator of innate immune response. Nature 448, 501-505.
82. Tang, D., Kang, R., Coyne, C. B., Zeh, H. J. & Lotze, M. T. (2012). PAMPs and DAMPs: signal 0s that spur autophagy and immunity. Immunol Rev 249, 158-175.
83. Tugnet, N., Rylance, P., Roden, D., Trela, M. & Nelson, P. (2013). Human endogenous retroviruses (HERVs) and autoimmune rheumatic disease: is there a link? Open Rheumatol J 7, 13-21.
84. Turner, M. D., Nedjai, B., Hurst, T. & Pennington, D. J. (2014). Cytokines and chemokines: at the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta 1843, 2563-2582.
85. Unterholzner, L., Keating, S. E., Baran, M., Horan, K. A., Jensen, S. B., Sharma, S., Sirois, C. M., Jin, T., Latz, E. & other authors (2010). IFI16 is an innate immune sensor for intracellular DNA. Nat Immunol 11, 997-1004.
86. Volkman, H. E. & Stetson, D. B. (2014). The enemy within: endogenous retroelements and autoimmune disease. Nat Immunol 15, 415-422.
87. Wang-Johanning, F., Radvanyi, L., Rycaj, K., Plummer, J. B., Yan, P., Sastry, K. J., Piyathilake, C. J., Hunt, K. K. & Johanning, G. L. (2008). Human endogenous retrovirus K triggers an antigen-specific immune response in breast cancer patients. Cancer Res 68, 5869-5877.
88. Wang-Johanning, F., Li, M., Esteva, F. J., Hess, K. R., Yin, B., Rycaj, K., Plummer, J. B., Garza, J. G., Ambs, S. & Johanning, G. L. (2014). Human endogenous retrovirus type K antibodies and mRNA as serum biomarkers of early-stage breast cancer. Int J Cancer 134, 587-595.
89. Xu, J., Zoltick, P. W., Gamero, A. M. & Gallucci, S. (2014). TLR ligands up-regulate Trex1 expression in murine conventional dendritic cells through type I interferon and NF-κB-dependent signaling pathways. J Leukoc Biol 96, 93-103.
90. Yan, N., Cherepanov, P., Daigle, J. E., Engelman, A. & Lieberman, J. (2009). The SET complex acts as a barrier to autointegration of HIV-1. PLoS Pathog 5, e1000327.
91. Yang, Y.-G., Lindahl, T. & Barnes, D. E. (2007). Trex1 exonuclease degrades ssDNA to prevent chronic checkpoint activation and autoimmune disease. Cell 131, 873-886.
92. Yap, M. W., Colbeck, E., Ellis, S. A. & Stoye, J. P. (2014). Evolution of the retroviral restriction gene Fv1: inhibition of non-MLV retroviruses. PLoS Pathog 10, e1003968.
93. Yoshinobu, K., Baudino, L., Santiago-Raber, M.-L., Morito, N., Dunand-Sauthier, I., Morley, B. J., Evans, L. H. & Izui, S. (2009). Selective up-regulation of intact, but not defective env RNAs of endogenous modified polytropic retrovirus by the Sgp3 locus of lupus-prone mice. J Immunol 182, 8094-8103.
94. Yu, P., Lübben, W., Slomka, H., Gebler, J., Konert, M., Cai, C., Neubrandt, L., Prazeres da Costa, O., Paul, S. & other authors (2012). Nucleic acid-sensing Toll-like receptors are essential for the control of endogenous retrovirus viremia and ERV-induced tumors. Immunity 37, 867-879.
95. Zuniga, E. I., Hahm, B. & Oldstone, M. B. A. (2007). Type I interferon during viral infections: multiple triggers for a multifunctional mediator. Curr Top Microbiol Immunol 316, 337-357.