How Flaviviruses Activate and Suppress the Interferon Response
Abstract
:Abbreviations
1. Detection of Flaviviruses by the Host Cell
2. Activation of RLR by Flaviviruses
3. Activation of TLRs
4. Evasion of the Host Recognition
5. Suppression of the IFN-α/β Signaling by Flaviviruses
6. Conclusions
Acknowledgments
References
- Bowie, A.G.; Haga, I.R. The role of Toll-like receptors in the host response to viruses. Mol. Immunol. 2005, 42, 859–867. [Google Scholar] [CrossRef] [PubMed]
- Yoneyama, M.; Kikuchi, M.; Matsumoto, K.; Imaizumi, T.; Miyagishi, M.; Taira, K.; Foy, E.; Loo, Y.M.; Gale Jr., M.; Akira, S. Shared and unique functions of the Dexd/H-box helicases RIG-I, MDA5, and LGP2 in antiviral innate immunity . J. Immunol. 2005, 175, 2851–2858. [Google Scholar] [PubMed]
- Yoneyama, M.; Kikuchi, M.; Natsukawa, T.; Shinobu, N.; Imaizumi, T.; Miyagishi, M.; Taira, K.; Akira, S.; Fujita, T. The RNA helicase RIG-I has an essential function in double-stranded RNA-induced innate antiviral responses. Nat. Immunol. 2004, 5, 730–737. [Google Scholar] [CrossRef] [PubMed]
- Andrejeva, J.; Childs, K.S.; Young, D.F.; Carlos, T.S.; Stock, N.; Goodbourn, S.; Randall, R.E. The V proteins of Paramyxoviruses bind the IFN-inducible RNA helicase, MDA-5, and inhibit its activation of the IFN-Beta promoter. Proc. Natl. Acad. Sci. USA 2004, 101, 17264–17269. [Google Scholar] [CrossRef]
- Kato, H.; Takeuchi, O.; Sato, S.; Yoneyama, M.; Yamamoto, M.; Matsui, K.; Uematsu, S.; Jung, A.; Kawai, T.; Ishii, K.J.; et al. Differential roles of MDA5 and RIG-I Helicases in the recognition of RNA viruses . Nature 2006, 441, 101–105. [Google Scholar] [CrossRef] [PubMed]
- Cui, S.; Eisenacher, K.; Kirchhofer, A.; Brzozka, K.; Lammens, A.; Lammens, K.; Fujita, T.; Conzelmann, K.K.; Krug, A.; Hopfner, K.P. The C-terminal regulatory domain is the RNA 5'-triphosphate sensor of RIG-I. Mol. Cell 2008, 29, 169–179. [Google Scholar] [CrossRef] [PubMed]
- Takahasi, K.; Yoneyama, M.; Nishihori, T.; Hirai, R.; Kumeta, H.; Narita, R.; Gale Jr., M.; Inagaki, F.; Fujita, T. Nonself RNA-sensing mechanism of RIG-I helicase and activation of antiviral immune responses . Mol. Cell 2008, 29, 428–440. [Google Scholar] [CrossRef] [PubMed]
- Hornung, V.; Ellegast, J.; Kim, S.; Brzozka, K.; Jung, A.; Kato, H.; Poeck, H.; Akira, S.; Conzelmann, K.K.; Schlee, M.; et al. 5'-Triphosphate RNA is the ligand for RIG-I . Science 2006, 314, 994–997. [Google Scholar] [CrossRef] [PubMed]
- Spiegel, M.; Pichlmair, A.; Martinez-Sobrido, L.; Cros, J.; Garcia-Sastre, A.; Haller, O.; Weber, F. Inhibition of beta interferon induction by severe acute respiratory syndrome coronavirus suggests a two-step model for activation of interferon regulatory factor 3. J. Virol. 2005, 79, 2079–2086. [Google Scholar] [CrossRef] [PubMed]
- Kato, H.; Takeuchi, O.; Mikamo-Satoh, E.; Hirai, R.; Kawai, T.; Matsushita, K.; Hiiragi, A.; Dermody, T.S.; Fujita, T.; Akira, S. Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid-inducible gene-I and melanoma differentiation-associated gene 5. J. Exp. Med. 2008, 205, 1601–1610. [Google Scholar] [CrossRef] [PubMed]
- Chang, T.H.; Liao, C.L.; Lin, Y.L. Flavivirus induces interferon-beta gene expression through a pathway involving RIG-I-dependent IRF-3 and PI3K-dependent NF-Kappab activation. Microbes Infect. 2006, 8, 157–171. [Google Scholar] [CrossRef]
- Loo, Y.M.; Fornek, J.; Crochet, N.; Bajwa, G.; Perwitasari, O.; Martinez-Sobrido, L.; Akira, S.; Gill, M.A.; Garcia-Sastre, A.; Katze, M.G.; et al. Distinct RIG-I and MDA5 signaling by RNA viruses in innate immunity . J. Virol. 2008, 82, 335–345. [Google Scholar] [CrossRef] [PubMed]
- Fredericksen, B.L.; Gale Jr., M. West Nile virus evades activation of interferon regulatory factor 3 through RIG-I-dependent and -independent pathways without antagonizing host defense signaling . J. Virol. 2006, 80, 291–2923. [Google Scholar] [CrossRef]
- Fredericksen, B.L.; Keller, B.C.; Fornek, J.; Katze, M.G.; Gale Jr., M. Establishment and maintenance of the innate antiviral response to West Nile virus involves both RIG-I and MDA5 signaling through IPS-1 . J. Virol. 2008, 82, 609–616. [Google Scholar] [CrossRef] [PubMed]
- Querec, T.D.; Akondy, R.S.; Lee, E.K.; Cao, W.; Nakaya, H.I.; Teuwen, D.; Pirani, A.; Gernert, K.; Deng, J.; Marzolf, B.; et al. Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans . Nat. Immunol. 2009, 10, 116–125. [Google Scholar] [CrossRef] [PubMed]
- Tsunobuchi, H.; Nishimura, H.; Goshima, F.; Daikoku, T.; Suzuki, H.; Nakashima, I.; Nishiyama, Y.; Yoshikai, Y. A protective role of Interleukin-15 in a mouse model for systemic infection with Herpes Simplex virus. Virology 2000, 275, 57–66. [Google Scholar] [CrossRef] [PubMed]
- Uematsu, S.; Akira, S. Toll-like receptors and type I interferons. J. Biol. Chem. 2007, 282, 15319–15323. [Google Scholar] [CrossRef] [PubMed]
- Diebold, S.S.; Kaisho, T.; Hemmi, H.; Akira, S.; Reis E Sousa, C. Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA. Science 2004, 303, 1529–1531. [Google Scholar] [CrossRef] [PubMed]
- Lund, J.M.; Alexopoulou, L.; Sato, A.; Karow, M.; Adams, N.C.; Gale, N.W.; Iwasaki, A.; Flavell, R.A. Recognition of single-stranded RNA viruses by Toll-like receptor 7. Proc. Natl. Acad. Sci. USA 2004, 101, 5598–5603. [Google Scholar] [CrossRef]
- Wang, J.P.; Liu, P.; Latz, E.; Golenbock, D.T.; Finberg, R.W.; Libraty, D.H. Flavivirus activation of plasmacytoid dendritic cells delineates key elements of TLR7 signaling beyond endosomal recognition. J. Immunol. 2006, 177, 7114–7121. [Google Scholar] [PubMed]
- Severa, M.; Fitzgerald, K.A. TLR-mediated activation of type I IFN during antiviral immune responses: fighting the battle to win the war. Curr. Top. Microbiol. Immunol. 2007, 316, 167–192. [Google Scholar] [PubMed]
- Tsai, Y.T.; Chang, S.Y.; Lee, C.N.; Kao, C.L. Human TLR3 recognizes Dengue virus and modulates viral replication In Vitro. Cell. Microbiol. 2009, 11, 604–615. [Google Scholar] [CrossRef] [PubMed]
- Aleyas, A.G.; George, J.A.; Han, Y.W.; Kim, H.K.; Kim, S.J.; Yoon, H.A.; Eo, S.K. Flaviviruses induce pro-inflammatory and anti-inflammatory cytokines from murine dendritic cells through Myd88-dependent pathway. Immune Network 2007, 66, 66–74. [Google Scholar]
- Wang, T.; Town, T.; Alexopoulou, L.; Anderson, J.F.; Fikrig, E.; Flavell, R.A. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nat. Med. 2004, 10, 1366–1373. [Google Scholar] [CrossRef] [PubMed]
- Daffis, S.; Samuel, M.A.; Suthar, M.S.; Gale Jr., M.; Diamond, M.S. Toll-like receptor 3 has a protective role against West Nile virus infection . J. Virol. 2008, 82, 10349–10358. [Google Scholar] [CrossRef] [PubMed]
- Welte, T.; Reagan, K.; Fang, H.; Machain-Williams, C.; Zheng, X.; Mendell, N.; Chang, G.J.; Wu, P.; Blair, C.D.; Wang, T. Toll-like receptor 7 induced immune response to cutaneous West Nile Virus infection. J. Gen. Virol. 2009, 90, 2660–2668. [Google Scholar] [CrossRef] [PubMed]
- Querec, T.; Bennouna, S.; Alkan, S. Yellow fever vaccine YF-17D Activates multiple dendritic cell subsets via TLR2, 7, 8, and 9 to stimulate polyvalent immunity. J. Exp. Med. 2006, 203, 413–424. [Google Scholar] [CrossRef] [PubMed]
- Elco, C.P.; Guenther, J.M.; Williams, B.R.; Sen, G.C. Analysis of genes induced by Sendai virus infection of mutant cell lines reveals essential roles of interferon regulatory factor 3, NF-kappaB, and interferon but not Toll-like receptor 3. J. Virol. 2005, 79, 3920–3929. [Google Scholar] [CrossRef] [PubMed]
- Busch, M.P.; Kleinman, S.H.; Jackson, B.; Stramer, S.L.; Hewlett, I.; Preston, S. Committee Report Nucleic acid amplification testing of blood donors for transfusion-transmitted infectious diseases: report of the interorganizational task force on nucleic acid amplification testing of blood donors. Transfusion 2000, 40, 143–159. [Google Scholar] [CrossRef] [PubMed]
- Shieh, W.J.; Jung, S.M.; Hsueh, C.; Kuo, T.T.; Mounts, A.; Parashar, U.; Yang, C.F.; Guarner, J.; Ksiazek, T.G.; Dawson, J.; et al. Pathologic studies of fatal cases in outbreak of hand, foot, and mouth disease, taiwan . Emerg. Infect. Dis. 2001, 7, 146–148. [Google Scholar] [CrossRef] [PubMed]
- Yoneyama, M.; Suhara, W.; Fukuhara, Y.; Fukuda, M.; Nishida, E.; Fujita, T. Direct triggering of the type I interferon system by virus infection: activation of a transcription factor complex containing IRF-3 and CBP/P300. Embo J. 1998, 17, 1087–1095. [Google Scholar] [CrossRef] [PubMed]
- tenOever, B.R.; Sharma, S; Zou, W.; Sun, Q.; Grandvaux, N.; Julkunen, I.; Hemmi, H.; Yamamoto, M.; Akira, S.; Yeh, W.C.; et al. Activation of TBK1 and ikkvarepsilon kinases by vesicular stomatitis virus infection and the role of viral ribonucleoprotein in the development of interferon antiviral immunity . J. Virol. 2004, 78, 10636–10649. [Google Scholar] [CrossRef] [PubMed]
- Fredericksen, B.; Akkaraju, G.R.; Foy, E.; Wang, C.; Pflugheber, J.; Chen, Z.J.; Gale. M., Jr. Activation of the interferon-beta promoter during Hepatitis C virus RNA replication. Viral Immunol. 2002, 15, 29–40. [Google Scholar] [PubMed]
- Daffis, S.; Samuel, M.A.; Keller, B.C.; Gale Jr., M.; Diamond, M.S. Cell-specific IRF-3 responses protect against West Nile virus infection by interferon-dependent and -independent mechanisms . Plos Pathog. 2007, 3, 1005–1015. [Google Scholar] [CrossRef]
- Fredericksen, B.L.; Smith, M.; Katze, M.G.; Shi; P.Y.; Gale Jr., M. The host response to West Nile Virus infection limits viral spread through the activation of the interferon regulatory factor 3 pathway . J. Virol. 2004, 78, 7737–7747. [Google Scholar] [CrossRef] [PubMed]
- Der, S.D.; Zhou, A.; Williams, B.R.; Silverman, R.H. Identification of genes differentially regulated by interferon alpha, beta, or gamma using oligonucleotide arrays. Proc. Natl. Acad. Sci. USA 1998, 95, 15623–15628. [Google Scholar] [CrossRef]
- Takaoka, A.; Yanai, H. Interferon signalling network in innate defence. Cell. Microbiol. 2006, 8, 907–922. [Google Scholar] [CrossRef] [PubMed]
- Diamond, M.S.; Harris, E. Interferon inhibits Dengue Virus infection by preventing translation of viral RNA through a PKR-independent mechanism. Virology 2001, 289, 297–311. [Google Scholar] [CrossRef] [PubMed]
- Scholle, F.; Mason, P.W. West Nile virus replication interferes with both Poly(I:C)-induced interferon gene transcription and response to interferon treatment. Virology 2005, 342, 77–87. [Google Scholar] [CrossRef] [PubMed]
- Keller, B.C.; Fredericksen, B.L.; Samuel, M.A.; Mock, R.E.; Mason, P.W.; Diamond, M.S.; Gale Jr., M. Resistance to alpha/beta interferon is a determinant of West Nile virus replication fitness and virulence . J. Virol. 2006, 80, 9424–9434. [Google Scholar] [CrossRef] [PubMed]
- Guo, J.T.; Hayashi, J.; Seeger, C. West Nile Virus inhibits the signal transduction pathway of alpha interferon. J. Virol. 2005, 79, 1343–1350. [Google Scholar] [CrossRef] [PubMed]
- Pantelic, L.; Sivakumaran, H.; Urosevic, N. Differential induction of antiviral effects against West Nile Virus in primary mouse macrophages derived from flavivirus-susceptible and congenic resistant mice by alpha/beta interferon and Poly(I-C). J. Virol. 2005, 79, 1753–1764. [Google Scholar] [CrossRef] [PubMed]
- Samuel, M.A.; Diamond, M.S. Alpha/Beta interferon protects against lethal West Nile virus infection by restricting cellular tropism and enhancing neuronal survival. J. Virol. 2005, 79, 13350–13361. [Google Scholar] [CrossRef] [PubMed]
- Lobigs, M.; Mullbacher, A.; Wang, Y.; Pavy, M.; Lee, E. Role of type I and Type II interferon responses in recovery from infection with an encephalitic flavivirus. J. Gen. Virol. 2003, 84, 567–572. [Google Scholar] [CrossRef] [PubMed]
- Johnson, A.J.; Roehrig, J.T. New Mouse Model For Dengue Virus Vaccine Testing. J. Virol. 1999, 73, 783–786. [Google Scholar] [PubMed]
- Shresta, S.; Sharar, K.L.; Prigozhin, D.M.; Beatty, P.R.; Harris, E. Murine model for dengue virus-induced lethal disease with increased vascular permeability. J. Virol. 2006, 80, 10208–10217. [Google Scholar] [CrossRef] [PubMed]
- Shresta, S.; Sharar, K.L.; Prigozhin, D.M.; Snider, H.M.; Beatty, P.R.; Harris, E. Critical roles for both STAT1-dependent and STAT1-independent pathways in the control of primary Dengue virus infection in mice. J. Immunol. 2005, 175, 3946–3954. [Google Scholar] [PubMed]
- Musso, T.; Gusella, G.L.; Brooks, A.; Longo, D.L.; Varesio, L. Interleukin-4 inhibits indoleamine 2,3-dioxygenase expression in human monocytes. Blood 1994, 83, 1408–1411. [Google Scholar] [PubMed]
- Warke, R.V.; Xhaja, K.; Martin, K.J.; Fournier, M.F.; Shaw, S.K.; Brizuela, N.; De Bosch, N.; Lapointe, D.; Ennis, F.A.; Rothman, A.L.; et al. Dengue virus induces novel changes in gene expression of human umbilical vein endothelial cells . J. Virol. 2003, 77, 11822–11832. [Google Scholar] [CrossRef] [PubMed]
- Warke, R.V.; Becerra, A.; Zawadzka, A.; Schmidt, D.J.; Martin, K.J.; Giaya, K.; Dinsmore, J.H.; Woda, M.; Hendricks, G.; Levine, T.; et al. Efficient Dengue virus (DENV) Infection of human muscle satellite cells upregulates type I interferon response genes and differentially modulates MHC I expression on bystander and DENV-infected cells . J. Gen. Virol. 2008, 89, 1605–1615. [Google Scholar] [CrossRef] [PubMed]
- Scherbik, S.V.; Stockman, B.M.; Brinton, M.A. Differential expression of interferon (IFN-) regulatory factors and IFN-stimulated genes at early times after West Nile virus infection of mouse embryo fibroblasts. J. Virol. 2007, 81, 12005–12018. [Google Scholar] [CrossRef] [PubMed]
- Daffis, S.; Samuel, M.A.; Suthar, M.S.; Keller, B.C.; Gale, M.; Diamond, M.S. Interferon regulatory factor IRF-7 induces the antiviral alpha interferon response and protects against lethal West Nile virus infection . J. Virol. 2008, 82, 8465–8475. [Google Scholar] [CrossRef] [PubMed]
- Sariol, C.A.; Munoz-Jordan, J.L.; Abel, K.; Rosado, L.C.; Pantoja, P.; Giavedoni, L.; Rodriguez, I.V.; White, L.J.; Martinez, M.; Arana, T.; et al. Transcriptional activation of interferon-stimulated genes but not of cytokine genes after primary infection of rhesus macaques with Dengue virus type 1 . Clin. Vaccine Immunol. 2007, 14, 756–766. [Google Scholar] [CrossRef] [PubMed]
- Fink, J.; Gu, F.; Ling, L.; Tolfvenstam, T.; Olfat, F.; Chin, K.C.; Aw, P.; George, J.; Kuznetsov, V.A.; Schreiber, M.; et al. Host gene expression profiling of Dengue virus infection in cell lines and patients . Plos Negl. Trop. Dis. 2007, 1, 1–11. [Google Scholar] [CrossRef]
- Ubol, S.; Masrinoul, P.; Chaijaruwanich, J.; Kalayanarooj, S.; Charoensirisuthikul, T.; Kasisith, J. Differences in global gene expression in peripheral blood mononuclear cells indicate a significant role of the innate responses in progression of Dengue fever but not Dengue hemorrhagic fever. J. Infect. Dis. 2008, 197, 1459–1467. [Google Scholar] [CrossRef] [PubMed]
- Libraty, D.H.; Young, P.R.; Pickering, D.; Endy, T.P.; Kalayanarooj, S.; Green, S.; Vaughn, D.W.; Nisalak, A.; Ennis, F.A.; Rothman, A.L. High circulating levels of the Dengue Virus nonstructural protein NS1 early in Dengue illness correlate with the development of Dengue Hemorrhagic fever. J. Infect. Dis. 2002, 186, 1165–1168. [Google Scholar] [CrossRef] [PubMed]
- Libraty, D.H.; Pichyangkul, S.; Ajariyakhajorn, C.; Endy, T.P.; Ennis, F.A. Human dendritic cells are activated by Dengue virus infection: enhancement by gamma interferon and implications for disease pathogenesis. J. Virol. 2001, 75, 3501–3508. [Google Scholar] [CrossRef] [PubMed]
- Pichyangkul, S.; Endy, T.P.; Kalayanarooj, S.; Nisalak, A.; Yongvanitchit, K.; Green, S.; Rothman, A.L.; Ennis, F.A.; Libraty, D.H. A blunted blood plasmacytoid dendritic cell response to an acute systemic viral infection is associated with increased disease severity. J. Immunol. 2003, 171, 5571–5578. [Google Scholar] [PubMed]
- Munoz-Jordan, J.L.; Sanchez-Burgos, G.G.; Laurent-Rolle, M.; Garcia-Sastre, A. Inhibition of interferon signaling by Dengue virus. Proc. Natl. Acad. Sci. USA 2003, 100, 14333–14338. [Google Scholar] [CrossRef]
- Munoz-Jordan, J.L.; Laurent-Rolle, M.; Ashour, J.; Martinez-Sobrido, L.; Ashok, M.; Lipkin, W.I.; Garcia-Sastre, A. hibition of alpha/beta interferon signaling by the NS4B protein of Flaviviruses. J. Virol. 2005, 79, 8004–8013. [Google Scholar] [CrossRef] [PubMed]
- Lundin, M.; Monne, M.; Widell, A.; Von Heijne, G.; Persson, M.A. Topology of the membrane-associated Hepatitis C virus protein NS4B. J. Virol. 2003, 77, 5428–5438. [Google Scholar] [CrossRef] [PubMed]
- Qu, L.; Mcmullan, L.K.; Rice, C.M. Isolation and characterization of noncytopathic pestivirus mutants reveals a role for nonstructural protein NS4B in viral cytopathogenicity. J. Virol. 2001, 75, 10651–10662. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.J.; Wang, X.J.; Mokhonov, V.V.; Shi, P.Y.; Randall, R; Khromykh, A.A. Inhibition of interferon signaling by the New York 99 strain and Kunjin subtype of West Nile Virus involves blockage of STAT1 and STAT2 activation by nonstructural proteins . J. Virol. 2005, 79, 1934–1942. [Google Scholar] [CrossRef] [PubMed]
- Jones, M.; Davidson, A.; Hibbert, L.; Gruenwald, P.; Schlaak, J.; Ball, S.; Foster, G.R.; Jacobs, M. Dengue virus inhibits alpha interferon signaling by reducing STAT2 expression. J. Virol. 2005, 79, 5414–5420. [Google Scholar] [CrossRef] [PubMed]
- Ashour, J.; Laurent-Rolle, M.; Shi, P.Y.; Garcia-Sastre, A. NS5 of Dengue virus mediates STAT2 binding and degradation. J. Virol. 2009, 83, 5408–5418. [Google Scholar] [CrossRef] [PubMed]
- Mazzon, M.; Jones, M.; Davidson, A.; Chain, B.; Jacobs, M. Dengue virus NS5 inhibits interferon-alpha signaling by blocking signal transducer and activator of transcription 2 phosphorylation. J. Infect. Dis. 2009, 200, 1261–1270. [Google Scholar] [CrossRef] [PubMed]
- Ho, L.J.; Hung, L.F.; Weng, C.Y.; Wu, W.L.; Chou, P.; Lin, Y.L.; Chang, D.M.; Tai, T.Y.; Lai, J.H. Dengue virus type 2 antagonizes IFN-alpha but not IFN-gamma antiviral effect via down-regulating Tyk2-STAT signaling in the human dendritic cell. J. Immunol. 2005, 174, 8163–8172. [Google Scholar] [PubMed]
- Lin, R.J.; Liao, C.L.; Lin, E.; Lin, Y.L. Blocking of the alpha interferon-induced Jak-Stat signaling pathway by japanese encephalitis virus infection. J. Virol. 2004, 78, 9285–9294. [Google Scholar] [CrossRef] [PubMed]
- Best, S.M.; Morris, K.L.; Shannon, J.G.; Robertson, S.J.; Mitzel, D.N.; Park, G.S.; Boer, E.; Wolfinbarger, J.B.; Bloom, M.E. Inhibition of interferon-stimulated JAK-STAT signaling by a tick-borne Flavivirus and identification of NS5 as an interferon antagonist. J. Virol. 2005, 79, 12828–12839. [Google Scholar] [CrossRef] [PubMed]
- Khromykh, A.A.; Sedlak, P.L.; Guyatt, K.J.; Hall, R.A.; Westaway, E.G. Efficient trans-complementation of the Flavivirus Kunjin NS5 protein but not of the NS1 Protein requires its coexpression with other components of the viral replicase. J. Virol. 1999, 73, 10272–10280. [Google Scholar] [PubMed]
- Meylan, E.; Tschopp, J. Toll-like receptors and RNA helicases: Two parallel ways to trigger antiviral responses. Mol. Cell 2006, 22, 561–569. [Google Scholar] [CrossRef] [PubMed]
- Lin, R.; Yang, L.; Nakhaei, P.; Sun, Q.; Sharif-Askari, E.; Julkunen, I.; Hiscott, J. Negative regulation of the retinoic acid-inducible gene I-induced antiviral state by the ubiquitin-editing protein A20. J. Biol. Chem. 2006, 281, 2095–2103. [Google Scholar] [CrossRef] [PubMed]
- Liu, W.J.; Chen, H.B.; Wang, X.J.; Huang, H.; Khromykh, A.A. Analysis of adaptive mutations in Kunjin virus replicon RNA reveals a novel role for the flavivirus nonstructural protein NS2A In inhibition of beta interferon promoter-driven transcription. J. Virol. 2004, 78, 12225–12235. [Google Scholar] [CrossRef] [PubMed]
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Muñoz-Jordán, J.L.; Fredericksen, B.L. How Flaviviruses Activate and Suppress the Interferon Response. Viruses 2010, 2, 676-691. https://doi.org/10.3390/v2020676
Muñoz-Jordán JL, Fredericksen BL. How Flaviviruses Activate and Suppress the Interferon Response. Viruses. 2010; 2(2):676-691. https://doi.org/10.3390/v2020676
Chicago/Turabian StyleMuñoz-Jordán, Jorge L., and Brenda L. Fredericksen. 2010. "How Flaviviruses Activate and Suppress the Interferon Response" Viruses 2, no. 2: 676-691. https://doi.org/10.3390/v2020676