Innate Antiviral Response: Role in HIV-1 Infection
Abstract
:1. Introduction
2. Transcription Factors of the IRF Family
2.1. The Viral IRF: KSHV-Encoded Viral IRF
2.2. IRF Mediated Cross Talk between Innate and Adaptive Immune Response
3. Induction of the Antiviral Response
3.1. The Role of IRF in Toll Receptor Mediated Antiviral Pathway
3.2. The Role of CARD-containing Proteins in Activation of IRF-3
3.3. Recognition of DNA Viruses
4. Interferon-Stimulated Genes: Mediators of the Antiviral Effects
5. Viral Strategy to Overcome the Antiviral Response
6. Role of the Innate Immune Response in HIV-1 Infection
6.1. HIV-1 Infection in vitro Induces Interferon Signature
6.2. Factors Counteracting the Antiviral Response to HIV-1 Infection
7. Reflections and Future Considerations
Acknowledgements
References and Notes
- Akira, S.; Takeda, K.; Kaisho, T. Toll-like receptors: Critical proteins linking innate and acquired immunity. Nat. Immunol. 2001, 2, 675–680. [Google Scholar] [CrossRef] [PubMed]
- Taniguchi, T.; Ogasawara, K.; Takaoka, A.; Tanaka, N. IRF family of transcription factors as regulators of host defense. Annu. Rev. Immunol. 2001, 19, 623–655. [Google Scholar] [CrossRef] [PubMed]
- Barnes, B.J.; Moore, P.A.; Pitha, P.M. Virus-specific activation of a novel interferon regulatory factor, IRF-5, results in the induction of distinct interferon alpha genes. J. Biol. Chem. 2001, 276, 23382–23390. [Google Scholar] [CrossRef] [PubMed]
- Iwasaki, A.; Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nat. Immunol. 2004, 5, 987–995. [Google Scholar] [CrossRef] [PubMed]
- Takaoka, A.; Yanai, H.; Kondo, S.; Duncan, G.; Negishi, H.; Mizutani, T.; Kano, S.; Honda, K.; Ohba, Y.; Mak, T.W.; Taniguchi, T. Integral role of IRF-5 in the gene induction programme activated by Toll-like receptors. Nature 2005, 434, 243–249. [Google Scholar] [CrossRef]
- Barnes, B.; Lubyova, B.; Pitha, P.M. On the role of IRF in host defense. J. Interferon Cytokine Res. 2002, 22, 59–71. [Google Scholar] [CrossRef]
- Escalante, C.R.; Yie, J.; Thanos, D.; Aggarwal, A.K. Expression, purification, and co-crystallization of IRF-I bound to the interferon-beta element PRDI. FEBS Lett. 1997, 414, 219–220. [Google Scholar]
- Takaoka, A.; Taniguchi, T. Cytosolic DNA recognition for triggering innate immune responses. Adv. Drug Deliv. Rev. 2008, 60, 847–857. [Google Scholar] [CrossRef]
- Fujita, T.; Sakakibara, J.; Sudo, Y.; Miyamoto, M.; Kimura, Y.; Taniguchi, T. IRF-1, mediating induction and silencing properties to human IFN-á gene regulatory elements. EMBO J. 1988, 7, 3397–3405. [Google Scholar] [CrossRef]
- Reis, L.F.; Ruffner, H.; Stark, G.; Aguet, M.; Weissmann, C. Mice devoid of interferon regulatory factor 1 (IRF-1) show normal expression of type I interferon genes. EMBO J. 1994, 13, 4798–4806. [Google Scholar] [CrossRef]
- Au, W.C.; Yeow, W.S.; Pitha, P.M. Analysis of functional domains of interferon regulatory factor 7 and its association with IRF-3. Virology 2001, 280, 273–282. [Google Scholar] [CrossRef]
- Marie, I.; Durbin, J.E.; Levy, D.E.s. Differential viral induction of distinct interferon-alpha genes by positive feedback through interferon regulatory factor-7. EMBO J. 1998, 17, 6660–6669. [Google Scholar] [CrossRef]
- Au, W.C.; Pitha, P.M. Recruitment of multiple interferon regulatory factors and histone acetyltransferase to the transcriptionally active interferon a promoters. J. Biol. Chem. 2001, 276, 41629–41637. [Google Scholar] [CrossRef]
- Au, W.-C.; Moore, P.A.; Lowther, W.; Juang, Y.-T.; Pitha, P.M. Identification of a member of the interferon regulatory factor family that binds to the interferon-stimulated response element and activates expression of interferon-induced genes. Proc. Natl. Acad. Sci. U. S. A. 1995, 92, 11657–11661. [Google Scholar] [CrossRef]
- Ronco, L.V.; Karpova, A.Y.; Vidal, M.; Howley, P.M. Human papillomavirus 16 E6 oncoprotein binds to interferon regulatory factor-3 and inhibits its transcriptional activity. Genes Dev. 1998, 12, 2061–2072. [Google Scholar] [CrossRef]
- Au, W.C.; Moore, P.A.; LaFleur, D.W.; Tombal, B.; Pitha, P.M. Characterization of the interferon regulatory factor-7 and its potential role in the transcription activation of interferon A genes. J. Biol. Chem. 1998, 273, 29210–29217. [Google Scholar] [CrossRef]
- Akira, S. TLR signaling. Curr. Top. Microbiol. Immunol. 2006, 311, 1–16. [Google Scholar]
- Yeow, W.S.; Au, W.C.; Juang, Y.T.; Fields, C.D.; Dent, C.L.; Gewert, D.R.; Pitha, P.M. Reconstitution of virus-mediated expression of interferon alpha genes in human fibroblast cells by ectopic interferon regulatory factor-7. J. Biol. Chem. 2000, 275, 6313–6320. [Google Scholar] [CrossRef]
- Gibson, S.J.; Lindh, J.M.; Riter, T.R.; Gleason, R.M.; Rogers, L.M.; Fuller, A.E.; Oesterich, J.L.; Gorden, K.B.; Qiu, X.; McKane, S.W.; et al. Plasmacytoid dendritic cells produce cytokines and mature in response to the TLR7 agonists, imiquimod and resiquimod. Cell. Immunol. 2002, 218, 74–86. [Google Scholar] [CrossRef]
- Siegal, F.P.; Kadowaki, N.; Shodell, M.; Fitzgerald-Bocarsly, P.A.; Shah, K.; Ho, S.; Antonenko, S.; Liu, Y.J. The nature of the principal type 1 interferon-producing cells in human blood. Science 1999, 284, 1835–1837. [Google Scholar] [CrossRef]
- Barnes, B.J.; Richards, J.; Mancl, M.; Hanash, S.; Beretta, L.; Pitha, P.M. Global and distinct targets of IRF-5 and IRF-7 during innate response to viral infection. J. Biol. Chem. 2004, 279, 45194–45207. [Google Scholar] [CrossRef] [PubMed]
- Honda, K.; Yanai, H.; Negishi, H.; Asagiri, M.; Sato, M.; Mizutani, T.; Shimada, N.; Ohba, Y.; Takaoka, A.; Yoshida, N.; Taniguchi, T. IRF-7 is the master regulator of type-I interferon-dependent immune responses. Nature 2005, 434, 772–777. [Google Scholar] [CrossRef] [PubMed]
- Paun, A.; Pitha, P.M. The innate antiviral response: New insights into a continuing story. Adv. Virus Res. 2007, 69, 1–66. [Google Scholar] [PubMed]
- Takaoka, A.; Tamura, T.; Taniguchi, T. Interferon regulatory factor family of transcription factors and regulation of oncogenesis. Cancer Sci. 2008, 99, 467–478. [Google Scholar] [CrossRef]
- Paun, A.; Bankoti, R.; Joshi, T.; Pitha, P.M.; Stager, S. Critical role of IRF-5 in the development of T helper 1 responses to Leishmania donovani infection. PLoS Pathog. 2011, 7, e1001246. [Google Scholar] [CrossRef]
- Lien, C.; Fang, C.M.; Huso, D.; Livak, F.; Lu, R.; Pitha, P.M. Critical role of IRF-5 in regulation of B-cell differentiation. Proc. Natl. Acad. Sci. U. S. A. 2010, 107, 4664–4668. [Google Scholar] [CrossRef]
- Krausgruber, T.; Blazek, K.; Smallie, T.; Alzabin, S.; Lockstone, H.; Sahgal, N.; Hussell, T.; Feldmann, M.; Udalova, I.A. IRF5 promotes inflammatory macrophage polarization and TH1-TH17 responses. Nat. Immunol. 2011, 12, 231–238. [Google Scholar] [CrossRef]
- Moore, P.S.; Chang, Y. Antiviral activity of tumor-suppressor pathways: Clues from molecular piracy by KSHV. Trends Genet. 1998, 14, 144–150. [Google Scholar] [CrossRef]
- Cunningham, C.; Barnard, S.; Blackbourn, D.J.; Davison, A.J. Transcription mapping of human herpesvirus 8 genes encoding viral interferon regulatory factors. J. Gen. Virol. 2003, 84, 1471–1483. [Google Scholar] [CrossRef]
- Burysek, L.; Yeow, W.S.; Lubyova, B.; Kellum, M.; Schafer, S.L.; Huang, Y.Q.; Pitha, P.M. Functional analysis of human herpesvirus 8-encoded viral interferon regulatory factor 1 and its association with cellular interferon regulatory factors and p300. J. Virol. 1999, 73, 7334–7342. [Google Scholar] [CrossRef]
- Flowers, C.C.; Flowers, S.P.; Nabel, G.J. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor confers resistance to the antiproliferative effect of interferon-alpha. Mol. Med. 1998, 4, 402–412. [Google Scholar] [CrossRef]
- Gao, S.J.; Boshoff, C.; Jayachandra, S.; Weiss, R.A.; Chang, Y.; Moore, P.S. KSHV ORF K9 (vIRF) is an oncogene which inhibits the interferon signaling pathway. Oncogene 1997, 15, 1979–1985. [Google Scholar] [CrossRef]
- Li, M.; Lee, H.; Guo, J.; Neipel, F.; Fleckenstein, B.; Ozato, K.; Jung, J.U. Kaposi's sarcoma-associated herpesvirus viral interferon regulatory factor. J. Virol. 1998, 72, 5433–5440. [Google Scholar] [CrossRef]
- Burysek, L.; Yeow, W.S.; Pitha, P.M. Unique properties of a second human herpesvirus 8-encoded interferon regulatory factor (vIRF-2). J. Hum. Virol. 1999, 2, 19–32. [Google Scholar]
- Burysek, L.; Pitha, P.M. Latently expressed human herpesvirus 8-encoded interferon regulatory factor 2 inhibits double-stranded RNA-activated protein kinase. J. Virol. 2001, 75, 2345–2352. [Google Scholar] [CrossRef]
- Lubyova, B.; Pitha, P.M. Characterization of a novel human herpesvirus 8-encoded protein, vIRF-3, that shows homology to viral and cellular interferon regulatory factors. J. Virol. 2000, 74, 8194–8201. [Google Scholar] [CrossRef]
- Rivas, C.; Thlick, A.E.; Parravicini, C.; Moore, P.S.; Chang, Y. Kaposi's sarcoma-associated herpesvirus LANA2 is a B-cell-specific latent viral protein that inhibits p53. J. Virol. 2001, 75, 429–438. [Google Scholar] [CrossRef]
- Lubyova, B.; Kellum, M.J.; Frisancho, A.J.; Pitha, P.M. Kaposi's sarcoma-associated herpesvirus-encoded vIRF-3 stimulates the transcriptional activity of cellular IRF-3 and IRF-7. J. Biol. Chem. 2004, 279, 7643–7654. [Google Scholar] [CrossRef]
- Lubyova, B.; Kellum, M.J.; Frisancho, J.A.; Pitha, P.M. Stimulation of c-Myc transcriptional activity by vIRF-3 of Kaposi sarcoma-associated herpesvirus. J. Biol. Chem. 2007, 282, 31944–31953. [Google Scholar] [CrossRef]
- Ducan, G.S.; Mittrucker, H.-W.; Kagi, D.; Matsuyama, T.; Mak, T.W. The transcription factor interferon regulatory factor-1 is essential for natural killer cell function in vivo. J. Exp. Med. 1996, 184, 2043–2048. [Google Scholar] [CrossRef]
- Lohoff, M.; Ferrick, D.; Mittrucker, H.W.; Duncan, G.S.; Bischof, S.; Rollinghoff, M.; Mak, T.W. Interferon regulatory factor-1 is required for a T helper 1 immune response in vivo. Immunity 1997, 6, 681–689. [Google Scholar] [CrossRef] [PubMed]
- Mittrucker, H.-W.; Matasuyama, T.; Grossman, A.; Kundig, T.M.; Potter, J.; Shahinian, A.; Wakeham, A.; Patterson, B.; Ohashi, P.; Mak, T. Requirement for the transcription factor LSIRF/IRF4 for mature B and T lymphocyte function. Science 1997, 275, 540–543. [Google Scholar] [CrossRef] [PubMed]
- Klein, U.; Casola, S.; Cattoretti, G.; Shen, Q.; Lia, M.; Mo, T.; Ludwig, T.; Rajewsky, K.; Dalla-Favera, R. Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination. Nat. Immunol. 2006, 7, 773–782. [Google Scholar] [CrossRef] [PubMed]
- Tamura, T.; Nagamura-Inoue, T.; Shmeltzer, Z.; Kuwata, T.; Ozato, K. ICSBP directs bipotential myeloid progenitor cells to differentiate into mature macrophages. Immunity 2000, 13, 155–165. [Google Scholar] [CrossRef] [PubMed]
- Tamura, T.; Thotakura, P.; Tanaka, T.S.; Ko, M.S.; Ozato, K. Identification of target genes and a unique cis element regulated by IRF-8 in developing macrophages. Blood 2005, 106, 1938–1947. [Google Scholar] [CrossRef]
- Lu, R.; Pitha, P.M. Monocyte differentiation to macrophage requires interferon regulatory factor 7. J. Biol. Chem. 2001, 276, 45491–45496. [Google Scholar] [CrossRef]
- Sasaki, S.; Amara, R.R.; Yeow, W.S.; Pitha, P.M.; Robinson, H.L. Regulation of DNA-raised immune responses by cotransfected interferon regulatory factors. J. Virol. 2002, 76, 6652–6659. [Google Scholar] [CrossRef]
- Maiwald, T.; Schneider, A.; Busch, H.; Sahle, S.; Gretz, N.; Weiss, T.S.; Kummer, U.; Klingmuller, U. Combining theoretical analysis and experimental data generation reveals IRF9 as a crucial factor for accelerating interferon alpha-induced early antiviral signalling. FEBS J. 2010, 277, 4741–4754. [Google Scholar] [CrossRef]
- Lin, C.H.; Hare, B.J.; Wagner, G.; Harrison, S.C.; Maniatis, T.; Fraenkel, E. A small domain of CBP/p300 binds diverse proteins: Solution structure and functional studies. Mol. Cell 2001, 8, 581–590. [Google Scholar] [CrossRef]
- Braganca, J.; Genin, P.; Bandu, M.T.; Darracq, N.; Vignal, M.; Casse, C.; Doly, J.; Civas, A. Synergism between multiple virus-induced factor-binding elements involved in the differential expression of interferon A genes. J. Biol. Chem. 1997, 272, 22154–22162. [Google Scholar] [CrossRef]
- Wathelet, M.G.; Lin, C.H.; Parekh, B.S.; Ronco, L.V.; Howley, P.M.; Maniatis, T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol. Cell 1998, 1, 507–518. [Google Scholar] [CrossRef]
- Medzhitov, R. CpG DNA: security code for host defense. Nat. Immunol. 2001, 2, 15–16. [Google Scholar] [CrossRef]
- Beutler, B.; Poltorak, A. Toll we meet again. Nat. Immunol. 2001, 2, 9–10. [Google Scholar] [CrossRef]
- Lin, S.C.; Lo, Y.C.; Wu, H. Helical assembly in the MyD88-IRAK4-IRAK2 complex in TLR/IL-1R signalling. Nature 2010, 465, 885–890. [Google Scholar] [CrossRef]
- Kawai, T.; Akira, S. Signaling to NF-kappaB by Toll-like receptors. Trends Mol. Med. 2007, 13, 460–469. [Google Scholar] [CrossRef]
- Izaguirre, A.; Barnes, B.J.; Amrute, S.; Yeow, W.S.; Megjugorac, N.; Dai, J.; Feng, D.; Chung, E.; Pitha, P.M.; Fitzgerald-Bocarsly, P. Comparative analysis of IRF and IFN-alpha expression in human plasmacytoid and monocyte-derived dendritic cells. J. Leukoc. Biol. 2003, 74, 1125–1138. [Google Scholar] [CrossRef]
- Matsumoto, M.; Oshiumi, H.; Seya, T. Antiviral responses induced by the TLR3 pathway. Rev. Med. Virol. 2011, 21, 67–77. [Google Scholar] [CrossRef]
- Fitzgerald, K.A.; McWhirter, S.M.; Faia, K.L.; Rowe, D.C.; Latz, E.; Golenbock, D.T.; Coyle, A.J.; Liao, S.M.; Maniatis, T. IKKepsilon and TBK1 are essential components of the IRF3 signaling pathway. Nat. Immunol. 2003, 4, 491–496. [Google Scholar] [CrossRef]
- Grandvaux, N.; Servant, M.J.; tenOever, B.; Sen, G.C.; Balachandran, S.; Barber, G.N.; Lin, R.; Hiscott, J. Transcriptional profiling of interferon regulatory factor 3 target genes: Direct involvement in the regulation of interferon-stimulated genes. J. Virol. 2002, 76, 5532–5539. [Google Scholar] [CrossRef]
- Fitzgerald, K.A.; Rowe, D.C.; Barnes, B.J.; Caffrey, D.R.; Visintin, A.; Latz, E.; Monks, B.; Pitha, P.M.; Golenbock, D.T. LPS-TLR4 signaling to IRF-3/7 and NF-kappaB involves the toll adapters TRAM and TRIF. J. Exp. Med. 2003, 198, 1043–1055. [Google Scholar] [CrossRef]
- Hoebe, K.; Du, X.; Georgel, P.; Janssen, E.; Tabeta, K.; Kim, S.O.; Goode, J.; Lin, P.; Mann, N.; Mudd, S.; et al. Identification of Lps2 as a key transducer of MyD88-independent TIR signalling. Nature 2003, 424, 743–748. [Google Scholar] [CrossRef] [PubMed]
- Fitzgerald, K.A.; Palsson-McDermott, E.M.; Bowie, A.G.; Jefferies, C.A.; Mansell, A.S.; Brady, G.; Brint, E.; Dunne, A.; Gray, P.; Harte, M.T.; et al. Mal (MyD88-adapter-like) is required for Toll-like receptor-4 signal transduction. Nature 2001, 413, 78–83. [Google Scholar] [CrossRef] [PubMed]
- Honda, K.; Takaoka, A.; Taniguchi, T. Type I interferon [corrected] gene induction by the interferon regulatory factor family of transcription factors. Immunity 2006, 25, 349–360. [Google Scholar] [CrossRef] [PubMed]
- Haller, O.; Kochs, G.; Weber, F. The interferon response circuit: induction and suppression by pathogenic viruses. Virology 2006, 344, 119–130. [Google Scholar] [CrossRef] [PubMed]
- Chuang, T.H.; Ulevitch, R.J. Cloning and characterization of a sub-family of human toll-like receptors: hTLR7, hTLR8 and hTLR9. Eur. Cytokine Netw. 2000, 11, 372–378. [Google Scholar]
- Hemmi, H.; Takeuchi, O.; Kawai, T.; Kaisho, T.; Sato, S.; Sanjo, H.; Matsumoto, M.; Hoshino, K.; Wagner, H.; Takeda, K.; et al. A Toll-like receptor recognizes bacterial DNA. Nature 2000, 408, 740–745. [Google Scholar] [CrossRef]
- 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]
- 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. U. S. A. 2004, 101, 5598–5603. [Google Scholar] [CrossRef]
- Schoenemeyer, A.; Barnes, B.J.; Mancl, M.E.; Latz, E.; Goutagny, N.; Pitha, P.M.; Fitzgerald, K.A.; Golenbock, D.T. The interferon regulatory factor, IRF5, is a central mediator of toll-like receptor 7 signaling. J. Biol. Chem. 2005, 280, 17005–17012. [Google Scholar] [CrossRef]
- Balkhi, M.Y.; Fitzgerald, K.A.; Pitha, P.M. Functional regulation of MyD88-activated interferon regulatory factor 5 by K63-linked polyubiquitination. Mol. Cell. Biol. 2008, 28, 7296–7308. [Google Scholar] [CrossRef] [PubMed]
- Yoneyama, M.; Kikuchi, M.; Matsumoto, K.; Imaizumi, T.; Miyagishi, M.; Taira, K.; Foy, E.; Loo, Y.M.; Gale, M., Jr.; Akira, S.; et al. 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] [CrossRef] [PubMed]
- 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]
- Kawai, T.; Akira, S. Antiviral signaling through pattern recognition receptors. J. Biochem. 2007, 141, 137–145. [Google Scholar] [CrossRef]
- Sato, A.; Linehan, M.M.; Iwasaki, A. Dual recognition of herpes simplex viruses by TLR2 and TLR9 in dendritic cells. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 17343–17348. [Google Scholar] [CrossRef]
- Sorensen, L.N.; Reinert, L.S.; Malmgaard, L.; Bartholdy, C.; Thomsen, A.R.; Paludan, S.R. TLR2 and TLR9 synergistically control herpes simplex virus infection in the brain. J. Immunol. 2008, 181, 8604–8612. [Google Scholar] [CrossRef]
- Compton, T.; Kurt-Jones, E.A.; Boehme, K.W.; Belko, J.; Latz, E.; Golenbock, D.T.; Finberg, R.W. Human cytomegalovirus activates inflammatory cytokine responses via CD14 and Toll-like receptor 2. J. Virol. 2003, 77, 4588–4596. [Google Scholar] [CrossRef]
- Rathinam, V.A.; Jiang, Z.; Waggoner, S.N.; Sharma, S.; Cole, L.E.; Waggoner, L.; Vanaja, S.K.; Monks, B.G.; Ganesan, S.; Latz, E.; et al. The AIM2 inflammasome is essential for host defense against cytosolic bacteria and DNA viruses. Nat. Immunol. 2010, 11, 395–402. [Google Scholar] [CrossRef]
- Ishikawa, H.; Ma, Z.; Barber, G.N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 2009, 461, 788–792. [Google Scholar] [CrossRef]
- Ishii, K.J.; Akira, S. Innate immune recognition of, and regulation by, DNA. Trends Immunol. 2006, 27, 525–532. [Google Scholar] [CrossRef]
- Wang, Z.; Choi, M.K.; Ban, T.; Yanai, H.; Negishi, H.; Lu, Y.; Tamura, T.; Takaoka, A.; Nishikura, K.; Taniguchi, T. Regulation of innate immune responses by DAI (DLM-1/ZBP1) and other DNA-sensing molecules. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 5477–5482. [Google Scholar] [CrossRef]
- Unterholzner, L.; Keating, S.E.; Baran, M.; Horan, K.A.; Jensen, S.B.; Sharma, S.; Sirois, C.M.; Jin, T.; Latz, E.; Xiao, T.S.; et al. IFI16 is an innate immune sensor for intracellular DNA. Nat. Immunol. 2010, 11, 997–1004. [Google Scholar] [CrossRef] [PubMed]
- Ablasser, A.; Bauernfeind, F.; Hartmann, G.; Latz, E.; Fitzgerald, K.A.; Hornung, V. RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III-transcribed RNA intermediate. Nat. Immunol. 2009, 10, 1065–1072. [Google Scholar] [CrossRef] [PubMed]
- Kanneganti, T.D. Central roles of NLRs and inflammasomes in viral infection. Nat. Rev. Immunol. 2010, 10, 688–698. [Google Scholar] [CrossRef] [PubMed]
- Muller, U.; Steinhoff, U.; Reis, L.F.; Hemmi, S.; Pavlovic, J.; Zinkernagel, R.M.; Aguet, M. Functional role of type I and type II interferons in antiviral defense. Science 1994, 264, 1918–1921. [Google Scholar] [CrossRef] [PubMed]
- Dupuis, S.; Jouanguy, E.; Al-Hajjar, S.; Fieschi, C.; Al-Mohsen, I.Z.; Al-Jumaah, S.; Yang, K.; Chapgier, A.; Eidenschenk, C.; Eid, P.; et al. Impaired response to interferon-alpha/beta and lethal viral disease in human STAT1 deficiency. Nat. Genet. 2003, 33, 388–391. [Google Scholar] [CrossRef]
- Bouloy, M.; Janzen, C.; Vialat, P.; Khun, H.; Pavlovic, J.; Huerre, M.; Haller, O. Genetic evidence for an interferon-antagonistic function of rift valley fever virus nonstructural protein NSs. J. Virol. 2001, 75, 1371–1377. [Google Scholar] [CrossRef]
- Darnell, J.E.J.; Kerr, I.M.; Stark, G.R. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994, 264, 1415–1421. [Google Scholar] [CrossRef]
- 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. U. S. A. 1998, 95, 15623–15628. [Google Scholar] [CrossRef]
- Li, X.; Leung, S.; Qureshi, S.; Darnell, J.E.J.; Stark, G.R. Formation of STAT1-STAT2 heterodimers and their role in the activation of IRF-1 gene transcription by interferon-alpha. J. Biol.Chem. 1996, 271, 5790–5794. [Google Scholar] [CrossRef]
- Schindler, C.; Fu, X.-Y.; Improta, T.; Aebersold, R.; Darnell, J.E.J. Proteins of transcription factor ISGF-3: one gene encodes the 91- and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 7836–7839. [Google Scholar] [CrossRef]
- Darnell, J.E., Jr. STATs and gene regulation. Science 1997, 277, 1630–1635. [Google Scholar] [CrossRef]
- Levy, D.E.; Darnell, J.E., Jr. Stats: Transcriptional control and biological impact. Nat. Rev. Mol. Cell Biol. 2002, 3, 651–662. [Google Scholar] [CrossRef]
- Platanias, L.C. Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat. Rev. Immunol. 2005, 5, 375–386. [Google Scholar] [CrossRef]
- Samuel, C.E. Antiviral actions of interferons. Clin. Microbiol. Rev. 2001, 14, 778–809, table of contents. [Google Scholar] [CrossRef]
- Schoggins, J.W.; Wilson, S.J.; Panis, M.; Murphy, M.Y.; Jones, C.T.; Bieniasz, P.; Rice, C.M. A diverse range of gene products are effectors of the type I interferon antiviral response. Nature 2011, 472, 481–485. [Google Scholar] [CrossRef]
- Kerr, I.M.; Brown, R.E. pppA2'p5'A2'p5'A: An inhibitor of protein synthesis synthesized with an enzyme fraction from interferon-treated cells. Proc. Natl. Acad. Sci. U. S. A. 1978, 75, 256–260. [Google Scholar] [CrossRef]
- Samuel, C.E. The eIF-2 alpha protein kinases, regulators of translation in eukaryotes from yeasts to humans. J. Biol. Chem. 1993, 268, 7603–7606. [Google Scholar] [CrossRef]
- Kumar, A.; Haque, J.; Lacoste, J.; Hiscott, J.; Williams, B. Double stranded RNA-dependent protein kinase activates transcription factor NF-kB by phosphorylating IkB. Proc. Natl. Acad. Sci. U. S. A. 1994, 91, 6288–6292. [Google Scholar] [CrossRef]
- Staeheli, P.; Grob, R.; Meier, E.; Sutcliffe, J.G.; Haller, O. Influenza virus-susceptible mice carry Mx genes with a large deletion or a nonsense mutation. Mol. Cell. Biol. 1988, 8, 4518–4523. [Google Scholar]
- Haller, O.; Arnheiter, H.; Gresser, I.; Lindenmann, J. Virus-specific interferon action. Protection of newborn Mx carriers against lethal infection with influenza virus. J. Exp. Med. 1981, 154, 199–203. [Google Scholar] [CrossRef]
- Zhou, A.; Paranjape, J.M.; Der, S.D.; Williams, B.R.; Silverman, R.H. Interferon action in triply deficient mice reveals the existence of alternative antiviral pathways. Virology 1999, 258, 435–440. [Google Scholar] [CrossRef] [PubMed]
- Harty, R.N.; Pitha, P.M.; Okumura, A. Antiviral activity of innate immune protein ISG15. J. Innate. Immun. 2009, 1, 397–404. [Google Scholar] [CrossRef] [PubMed]
- Okumura, A.; Lu, G.; Pitha-Rowe, I.; Pitha, P.M. Innate antiviral response targets HIV-1 release by the induction of ubiquitin-like protein ISG15. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 1440–1445. [Google Scholar] [CrossRef] [PubMed]
- Okumura, A.; Pitha, P.M.; Harty, R.N. ISG15 inhibits Ebola VP40 VLP budding in an L-domain-dependent manner by blocking Nedd4 ligase activity. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 3974–3979. [Google Scholar] [CrossRef]
- Murphy, D.G.; Dimock, K.; Kang, C.Y. Numerous transitions in human parainfluenza virus 3 RNA recovered from persistently infected cells. Virology 1991, 181, 760–763. [Google Scholar] [CrossRef]
- Chen, K.; Huang, J.; Zhang, C.; Huang, S.; Nunnari, G.; Wang, F.X.; Tong, X.; Gao, L.; Nikisher, K.; Zhang, H. Alpha interferon potently enhances the anti-human immunodeficiency virus type 1 activity of APOBEC3G in resting primary CD4 T cells. J. Virol. 2006, 80, 7645–7657. [Google Scholar] [CrossRef]
- Yu, Q.; Chen, D.; Konig, R.; Mariani, R.; Unutmaz, D.; Landau, N.R. APOBEC3B and APOBEC3C are potent inhibitors of simian immunodeficiency virus replication. J. Biol. Chem. 2004, 279, 53379–53386. [Google Scholar] [CrossRef]
- Hou, J.; Wang, P.; Lin, L.; Liu, X.; Ma, F.; An, H.; Wang, Z.; Cao, X. MicroRNA-146a feedback inhibits RIG-I-dependent Type I IFN production in macrophages by targeting TRAF6, IRAK1, and IRAK2. J. Immunol. 2009, 183, 2150–2158. [Google Scholar] [CrossRef]
- O'Connell, R.M.; Taganov, K.D.; Boldin, M.P.; Cheng, G.; Baltimore, D. MicroRNA-155 is induced during the macrophage inflammatory response. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 1604–1609. [Google Scholar] [CrossRef]
- 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. U. S. A. 2004, 101, 17264–17269. [Google Scholar] [CrossRef]
- Precious, B.; Childs, K.; Fitzpatrick-Swallow, V.; Goodbourn, S.; Randall, R.E. Simian virus 5 V protein acts as an adaptor, linking DDB1 to STAT2, to facilitate the ubiquitination of STAT1. J. Virol. 2005, 79, 13434–13441. [Google Scholar] [CrossRef]
- Basler, C.F.; Mikulasova, A.; Martinez-Sobrido, L.; Paragas, J.; Muhlberger, E.; Bray, M.; Klenk, H.D.; Palese, P.; Garcia-Sastre, A. The Ebola virus VP35 protein inhibits activation of interferon regulatory factor 3. J. Virol. 2003, 77, 7945–7956. [Google Scholar] [CrossRef]
- Okumura, A.; Alce, T.; Lubyova, B.; Ezelle, H.; Strebel, K.; Pitha, P.M. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation. Virology 2008, 373, 85–97. [Google Scholar] [CrossRef]
- Ulane, C.M.; Kentsis, A.; Cruz, C.D.; Parisien, J.P.; Schneider, K.L.; Horvath, C.M. Composition and assembly of STAT-targeting ubiquitin ligase complexes: Paramyxovirus V protein carboxyl terminus is an oligomerization domain. J. Virol. 2005, 79, 10180–10189. [Google Scholar] [CrossRef]
- Alcami, A.; Symons, J.A.; Smith, G.L. The vaccinia virus soluble alpha/beta interferon (IFN) receptor binds to the cell surface and protects cells from the antiviral effects of IFN. J. Virol. 2000, 74, 11230–11239. [Google Scholar] [CrossRef]
- Ahmed, M.; McKenzie, M.O.; Puckett, S.; Hojnacki, M.; Poliquin, L.; Lyles, D.S. Ability of the matrix protein of vesicular stomatitis virus to suppress beta interferon gene expression is genetically correlated with the inhibition of host RNA and protein synthesis. J. Virol. 2003, 77, 4646–4657. [Google Scholar] [CrossRef]
- Haase, A.T. Targeting early infection to prevent HIV-1 mucosal transmission. Nature 2010, 464, 217–223. [Google Scholar] [CrossRef]
- Stacey, A.R.; Norris, P.J.; Qin, L.; Haygreen, E.A.; Taylor, E.; Heitman, J.; Lebedeva, M.; DeCamp, A.; Li, D.; Grove, D.; et al. Induction of a striking systemic cytokine cascade prior to peak viremia in acute human immunodeficiency virus type 1 infection, in contrast to more modest and delayed responses in acute hepatitis B and C virus infections. J. Virol. 2009, 83, 3719–3733. [Google Scholar] [CrossRef]
- Popik, W.; Pitha, P.M. Role of tumor necrosis factor alpha in activation and replication of the tat-defective human immunodeficiency virus type 1. J.Virol. 1993, 67, 1094–1099. [Google Scholar] [CrossRef]
- Sgarbanti, M.; Remoli, A.L.; Marsili, G.; Ridolfi, B.; Borsetti, A.; Perrotti, E.; Orsatti, R.; Ilari, R.; Sernicola, L.; Stellacci, E.; et al. IRF-1 is required for full NF-kappaB transcriptional activity at the human immunodeficiency virus type 1 long terminal repeat enhancer. J. Virol. 2008, 82, 3632–3641. [Google Scholar] [CrossRef]
- Harman, A.N.; Lai, J.; Turville, S.; Samarajiwa, S.; Gray, L.; Marsden, V.; Mercier, S.; Jones, K.; Nasr, N.; Cumming, H.; et al. HIV infection of dendritic cells subverts the interferon induction pathway via IRF1 and inhibits type 1 interferon production. Blood 2011. [Google Scholar] [CrossRef] [PubMed]
- Van Lint, C.; Amella, C.A.; Emiliani, S.; John, M.; Jie, T.; Verdin, E. Transcription factor binding sites downstream of the human immunodeficiency virus type 1 transcription start site are important for virus infectivity. J. Virol. 1997, 71, 6113–6127. [Google Scholar] [CrossRef] [PubMed]
- Su, R.C.; Sivro, A.; Kimani, J.; Jaoko, W.; Plummer, F.A.; Ball, T.B. Epigenetic control of IRF1 responses in HIV-exposed seronegative versus HIV-susceptible individuals. Blood 2011, 117, 2649–2657. [Google Scholar] [CrossRef] [PubMed]
- Sodora, D.L.; Ross, T.M. Simian immunodeficiency virus pathogenesis. Curr. HIV Res. 2009, 7, 1. [Google Scholar] [CrossRef]
- Rotger, M.; Dang, K.K.; Fellay, J.; Heinzen, E.L.; Feng, S.; Descombes, P.; Shianna, K.V.; Ge, D.; Gunthard, H.F.; Goldstein, D.B.; et al. Genome-wide mRNA expression correlates of viral control in CD4+ T-cells from HIV-1-infected individuals. PLoS Pathog. 2010, 6, e1000781. [Google Scholar] [CrossRef]
- Smith, A.J.; Li, Q.; Wietgrefe, S.W.; Schacker, T.W.; Reilly, C.S.; Haase, A.T. Host genes associated with HIV-1 replication in lymphatic tissue. J. Immunol. 2010, 185, 5417–5424. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Lehmann, C.; Lafferty, M.; Garzino-Demo, A.; Jung, N.; Hartmann, P.; Fatkenheuer, G.; Wolf, J.S.; van Lunzen, J.; Romerio, F. Plasmacytoid dendritic cells accumulate and secrete interferon alpha in lymph nodes of HIV-1 patients. PLoS ONE 2010, 5, e11110. [Google Scholar] [CrossRef]
- Hyrcza, M.D.; Kovacs, C.; Loutfy, M.; Halpenny, R.; Heisler, L.; Yang, S.; Wilkins, O.; Ostrowski, M.; Der, S.D. Distinct transcriptional profiles in ex vivo CD4+ and CD8+ T cells are established early in human immunodeficiency virus type 1 infection and are characterized by a chronic interferon response as well as extensive transcriptional changes in CD8+ T cells. J. Virol. 2007, 81, 3477–3486. [Google Scholar] [CrossRef]
- 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. [Google Scholar] [CrossRef]
- Cameron, P.U.; Handley, A.J.; Baylis, D.C.; Solomon, A.E.; Bernard, N.; Purcell, D.F.; Lewin, S.R. Preferential infection of dendritic cells during human immunodeficiency virus type 1 infection of blood leukocytes. J. Virol. 2007, 81, 2297–2306. [Google Scholar] [CrossRef]
- Pope, M.; Betjes, M.G.; Romani, N.; Hirmand, H.; Cameron, P.U.; Hoffman, L.; Gezelter, S.; Schuler, G.; Steinman, R.M. Conjugates of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994, 78, 389–398. [Google Scholar] [CrossRef]
- Turville, S.G.; Santos, J.J.; Frank, I.; Cameron, P.U.; Wilkinson, J.; Miranda-Saksena, M.; Dable, J.; Stossel, H.; Romani, N.; Piatak, M., Jr.; et al. Immunodeficiency virus uptake, turnover, and 2-phase transfer in human dendritic cells. Blood 2004, 103, 2170–2179. [Google Scholar] [CrossRef]
- Lepelley, A.; Louis, S.; Sourisseau, M.; Law, H.K.; Pothlichet, J.; Schilte, C.; Chaperot, L.; Plumas, J.; Randall, R.E.; Si-Tahar, M.; et al. Innate sensing of HIV-infected cells. PLoS Pathog. 2011, 7, e1001284. [Google Scholar] [CrossRef]
- Manel, N.; Hogstad, B.; Wang, Y.; Levy, D.E.; Unutmaz, D.; Littman, D.R. A cryptic sensor for HIV-1 activates antiviral innate immunity in dendritic cells. Nature 2010, 467, 214–217. [Google Scholar] [CrossRef]
- Laguette, N.; Sobhian, B.; Casartelli, N.; Ringeard, M.; Chable-Bessia, C.; Segeral, E.; Yatim, A.; Emiliani, S.; Schwartz, O.; Benkirane, M. SAMHD1 is the dendritic- and myeloid-cell-specific HIV-1 restriction factor counteracted by Vpx. Nature 2011, 474, 654–657. [Google Scholar] [CrossRef]
- Malim, M.H.; Emerman, M. HIV-1 accessory proteins—Ensuring viral survival in a hostile environment. Cell Host Microbe 2008, 3, 388–398. [Google Scholar] [CrossRef]
- Neil, S.; Bieniasz, P. Human immunodeficiency virus, restriction factors, and interferon. J. Interferon Cytokine Res. 2009, 29, 569–580. [Google Scholar] [CrossRef]
- Sheehy, A.M.; Gaddis, N.C.; Choi, J.D.; Malim, M.H. Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 2002, 418, 646–650. [Google Scholar] [CrossRef]
- Trapp, S.; Derby, N.R.; Singer, R.; Shaw, A.; Williams, V.G.; Turville, S.G.; Bess, J.W., Jr.; Lifson, J.D.; Robbiani, M. Double-stranded RNA analog poly(I:C) inhibits human immunodeficiency virus amplification in dendritic cells via type I interferon-mediated activation of APOBEC3G. J. Virol. 2009, 83, 884–895. [Google Scholar] [CrossRef]
- Casartelli, N.; Sourisseau, M.; Feldmann, J.; Guivel-Benhassine, F.; Mallet, A.; Marcelin, A.G.; Guatelli, J.; Schwartz, O. Tetherin restricts productive HIV-1 cell-to-cell transmission. PLoS Pathog. 2010, 6, e1000955. [Google Scholar] [CrossRef] [PubMed]
- Ross, S.R. Are viruses inhibited by APOBEC3 molecules from their host species? PLoS Pathog. 2009, 5, e1000347. [Google Scholar] [CrossRef] [PubMed]
- Nisole, S.; Stoye, J.P.; Saib, A. TRIM family proteins: Retroviral restriction and antiviral defence. Nat. Rev. Microbiol. 2005, 3, 799–808. [Google Scholar] [CrossRef]
- Gack, M.U.; Shin, Y.C.; Joo, C.H.; Urano, T.; Liang, C.; Sun, L.; Takeuchi, O.; Akira, S.; Chen, Z.; Inoue, S.; Jung, J.U. TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity. Nature 2007, 446, 916–920. [Google Scholar] [CrossRef]
- Pitha, P.M.; Rowe, W.P.; Oxman, M.N. Effect of interferon on exogenous, endogenous, and chroniv murine leukemia virus infection. Virology 1976, 70, 324–338. [Google Scholar] [CrossRef] [PubMed]
- Baca-Regen, L.; Heinzinger, N.; Stevenson, M.; Gendelman, H.E. Alpha interferon-induced antiretroviral activities: Restriction of viral nucleic acid synthesis and progeny virion production in human immunodeficiency virus type 1-infected monocytes. J. Virol. 1994, 68, 7559–7565. [Google Scholar] [CrossRef]
- Goujon, C.; Malim, M.H. Characterization of the alpha interferon-induced postentry block to HIV-1 infection in primary human macrophages and T cells. J. Virol. 2010, 84, 9254–9266. [Google Scholar] [CrossRef]
- Shirazi, Y.; Pitha, P.M. Alpha interferon inhibits early stages of the human immunodeficiency virus type 1 replication cycle. J. Virol. 1992, 66, 1321–1328. [Google Scholar] [CrossRef]
- Cheney, K.M.; McKnight, A. Interferon-alpha mediates restriction of human immunodeficiency virus type-1 replication in primary human macrophages at an early stage of replication. PLoS ONE 2010, 5, e13521. [Google Scholar] [CrossRef]
- Kunzi, M.S.; Pitha, P.M. Role of interferon-stimulated gene ISG-15 in the interferon-omega-mediated inhibition of human immunodeficiency virus replication. J. Interferon Cytokine Res. 1996, 16, 919–927. [Google Scholar] [CrossRef]
- Kaletsky, R.L.; Francica, J.R.; Agrawal-Gamse, C.; Bates, P. Tetherin-mediated restriction of filovirus budding is antagonized by the Ebola glycoprotein. Proc. Natl. Acad. Sci. U. S. A. 2009, 106, 2886–2891. [Google Scholar] [CrossRef]
- Jouvenet, N.; Neil, S.J.; Zhadina, M.; Zang, T.; Kratovac, Z.; Lee, Y.; McNatt, M.; Hatziioannou, T.; Bieniasz, P.D. Broad-spectrum inhibition of retroviral and filoviral particle release by tetherin. J. Virol. 2009, 83, 1837–1844. [Google Scholar] [CrossRef]
- Chiu, Y.L.; Greene, W.C. APOBEC3G: an intracellular centurion. Philos. Trans. R. Soc. Lond. B Biol. Sci. 2009, 364, 689–703. [Google Scholar] [CrossRef]
- Douglas, J.L.; Viswanathan, K.; McCarroll, M.N.; Gustin, J.K.; Fruh, K.; Moses, A.V. Vpu directs the degradation of the human immunodeficiency virus restriction factor BST-2/Tetherin via a {beta}TrCP-dependent mechanism. J. Virol. 2009, 83, 7931–7947. [Google Scholar] [CrossRef]
- Goffinet, C.; Allespach, I.; Homann, S.; Tervo, H.M.; Habermann, A.; Rupp, D.; Oberbremer, L.; Kern, C.; Tibroni, N.; Welsch, S.; et al. HIV-1 antagonism of CD317 is species specific and involves Vpu-mediated proteasomal degradation of the restriction factor. Cell Host Microbe 2009, 5, 285–297. [Google Scholar] [CrossRef]
- Bour, S.; Schubert, U.; Strebel, K. The human immunodeficiency virus type 1 Vpu protein specifically binds to the cytoplasmic domain of CD4: implications for the mechanism of degradation. J. Virol. 1995, 69, 1510–1520. [Google Scholar] [CrossRef]
- Sauter, D.; Schindler, M.; Specht, A.; Landford, W.N.; Munch, J.; Kim, K.A.; Votteler, J.; Schubert, U.; Bibollet-Ruche, F.; Keele, B.F.; et al. Tetherin-driven adaptation of Vpu and Nef function and the evolution of pandemic and nonpandemic HIV-1 strains. Cell Host Microbe 2009, 6, 409–421. [Google Scholar] [CrossRef]
- Solis, M.; Nakhaei, P.; Jalalirad, M.; Lacoste, J.; Douville, R.; Arguello, M.; Zhao, T.; Laughrea, M.; Wainberg, M.A.; Hiscott, J. RIG-I-mediated antiviral signaling is inhibited in HIV-1 infection by a protease-mediated sequestration of RIG-I. J. Virol. 2011, 85, 1224–1236. [Google Scholar] [CrossRef]
- Yan, N.; Regalado-Magdos, A.D.; Stiggelbout, B.; Lee-Kirsch, M.A.; Lieberman, J. The cytosolic exonuclease TREX1 inhibits the innate immune response to human immunodeficiency virus type 1. Nat. Immunol. 2010, 11, 1005–1013. [Google Scholar] [CrossRef]
- Akhtar, L.N.; Benveniste, E.N. Viral exploitation of host SOCS protein functions. J. Virol. 2011, 85, 1912–1921. [Google Scholar] [CrossRef]
- Witwer, K.W.; Sisk, J.M.; Gama, L.; Clements, J.E. MicroRNA regulation of IFN-beta protein expression: rapid and sensitive modulation of the innate immune response. J. Immunol. 2010, 184, 2369–2376. [Google Scholar] [CrossRef] [PubMed]
- Bednarik, D.P.; Mosca, J.D.; Raj, N.B.K.; Pitha, P.M. Inhibition of human immunodeficiency virus (HIV) replication by HIV-trans-activated à2-interferon. Proc. Natl. Acad. Sci. U. S. A. 1989, 86, 4958–4962. [Google Scholar] [CrossRef] [PubMed]
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Pitha, P.M. Innate Antiviral Response: Role in HIV-1 Infection. Viruses 2011, 3, 1179-1203. https://doi.org/10.3390/v3071179
Pitha PM. Innate Antiviral Response: Role in HIV-1 Infection. Viruses. 2011; 3(7):1179-1203. https://doi.org/10.3390/v3071179
Chicago/Turabian StylePitha, Paula M. 2011. "Innate Antiviral Response: Role in HIV-1 Infection" Viruses 3, no. 7: 1179-1203. https://doi.org/10.3390/v3071179