Key Points
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Humans are constantly exposed to numerous viruses but the consequences of infection are different in different individuals.
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The outcome of hostβviral interactions depend on the dose and route of infection, viral virulence properties, as well as several host factors that mainly involve innate and adaptive immunity.
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Host factors that influence the outcome of viral infection include genetic factors, such as polymorphism in MHC alleles, mutations in genes encoding innate receptors, cytokines, chemokine receptors, age, the nature of endogenous and persistent infections and pre-exposure to other infections.
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The host has numerous anti-inflammatory activities that limit the extent of tissue damage caused by infections.
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Successful pathogens such as HIV, hepatitis B virus (HBV), HCV and herpesviruses persist either as chronic or latent infections in the host with or without causing immediate ill effects; however, they may have lethal consequences when the host is immunocompromised.
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Viruses that cause chronic infection influence immune cells to produce predominantly anti-inflammatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor-Ξ² (TGFΞ²), and they upregulate inhibitory receptors on effector T cells giving them an exhaustion phenotype.
Abstract
Many viruses infect humans and most are controlled satisfactorily by the immune system with limited damage to host tissues. Some viruses, however, do cause overt damage to the host, either in isolated cases or as a reaction that commonly occurs after infection. The outcome is influenced by properties of the infecting virus, the circumstances of infection and several factors controlled by the host. In this Review, we focus on host factors that influence the outcome of viral infection, including genetic susceptibility, the age of the host when infected, the dose and route of infection, the induction of anti-inflammatory cells and proteins, as well as the presence of concurrent infections and past exposure to cross-reactive agents.
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References
Munz, C., Lunemann, J. D., Getts, M. T. & Miller, S. D. Antiviral immune responses: triggers of or triggered by autoimmunity? Nature Rev. Immunol. 9, 246β258 (2009).
de Martel, C. & Franceschi, S. Infections and cancer: established associations and new hypotheses. Crit. Rev. Oncol. Hematol. 70, 183β194 (2009).
Tal, M. C. et al. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc. Natl Acad. Sci. USA 106, 2770β2775 (2009).
Pichlmair, A. & Reis e Sousa, C. Innate recognition of viruses. Immunity 27, 370β383 (2007).
Iwasaki, A. & Medzhitov, R. Toll-like receptor control of the adaptive immune responses. Nature Immunol. 5, 987β995 (2004).
Brooks, D. G. et al. Interleukin-10 determines viral clearance or persistence in vivo. Nature Med. 12, 1301β1309 (2006). This paper implicated the role of IL-10 in the persistence of LCMV infection of mice and showed the therapeutic value of its neutralization in achieving viral control.
Brady, M. T., MacDonald, A. J., Rowan, A. G. & Mills, K. H. Hepatitis C virus non-structural protein 4 suppresses Th1 responses by stimulating IL-10 production from monocytes. Eur. J. Immunol. 33, 3448β3457 (2003).
Hyodo, N., Nakamura, I. & Imawari, M. Hepatitis B core antigen stimulates interleukin-10 secretion by both T cells and monocytes from peripheral blood of patients with chronic hepatitis B virus infection. Clin. Exp. Immunol. 135, 462β466 (2004).
Brockman, M. A. et al. IL-10 is up-regulated in multiple cell types during viremic HIV infection and reversibly inhibits virus-specific T cells. Blood 114, 346β356 (2009).
Smit, J. J., Rudd, B. D. & Lukacs, N. W. Plasmacytoid dendritic cells inhibit pulmonary immunopathology and promote clearance of respiratory syncytial virus. J. Exp. Med. 203, 1153β1159 (2006).
Guidotti, L. G. et al. Viral clearance without destruction of infected cells during acute HBV infection. Science 284, 825β829 (1999).
Rehermann, B. Hepatitis C virus versus innate and adaptive immune responses: a tale of coevolution and coexistence. J. Clin. Invest. 119, 1745β1754 (2009).
Favre, D. et al. Critical loss of the balance between Th17 and T regulatory cell populations in pathogenic SIV infection. PLoS Pathog. 5, e1000295 (2009). This paper showed that T H 17 cells are induced after SIV infection and that the balance of T H 17 and T Reg cells is a crucial determinant in the progression of disease in pigtailed macaques but not in African green monkeys, in which T H 17 cells were progressively depleted by the virus.
Rowan, A. G. et al. Hepatitis C virus-specific Th17 cells are suppressed by virus-induced TGF-Ξ². J. Immunol. 181, 4485β4494 (2008). This is the first study to show that viral antigen-specific T H 17 cells are induced in HCV-infected individuals and that viral protein (NS4)-induced TGFΞ² can inhibit the activity of T H 17 cells.
Bermejo-Martin, J. F. et al. Th1 and Th17 hypercytokinemia as early host response signature in severe pandemic influenza. Crit. Care 13, R201 (2009).
Culley, F. J., Pennycook, A. M., Tregoning, J. S., Hussell, T. & Openshaw, P. J. Differential chemokine expression following respiratory virus infection reflects Th1- or Th2-biased immunopathology. J. Virol. 80, 4521β4527 (2006).
Ravetch, J. In vivo veritas: the surprising roles of Fc receptors in immunity. Nature Immunol. 11, 183β185 (2010).
Buchmeier, M. J. & Oldstone, M. B. Virus-induced immune complex disease: identification of specific viral antigens and antibodies deposited in complexes during chronic lymphocytic choriomeningitis virus infection. J. Immunol. 120, 1297β1304 (1978). This is the first report in which immune complex deposits were measured using sensitive immunofluorescence and radioimmunoprecipitation in the tissue sites after a viral infection.
Nowoslawski, A., Krawczynski, K., Nazarewicz, T. & Slusarczyk, J. Immunopathological aspects of hepatitis type B. Am. J. Med. Sci. 270, 229β239 (1975).
Johnson, R. J. et al. Membranoproliferative glomerulonephritis associated with hepatitis C virus infection. N. Engl. J. Med. 328, 465β470 (1993).
Kimmel, P. L. et al. Brief report: idiotypic IgA nephropathy in patients with human immunodeficiency virus infection. N. Engl. J. Med. 327, 702β706 (1992).
Dakhama, A. et al. Virus-specific IgE enhances airway responsiveness on reinfection with respiratory syncytial virus in newborn mice. J. Allergy Clin. Immunol. 123, 138β145 (2009).
Couper, K. N., Blount, D. G. & Riley, E. M. IL-10: the master regulator of immunity to infection. J. Immunol. 180, 5771β5777 (2008).
Vieira, P. et al. Isolation and expression of human cytokine synthesis inhibitory factor cDNA clones: homology to Epstein-Barr virus open reading frame BCRFI. Proc. Natl Acad. Sci. USA 88, 1172β1176 (1991).
Kotenko, S. V., Saccani, S., Izotova, L. S., Mirochnitchenko, O. V. & Pestka, S. Human cytomegalovirus harbors its own unique IL-10 homolog (cmvIL-10). Proc. Natl Acad. Sci. USA 97, 1695β1700 (2000).
Moore, K. W., de Waal Malefyt, R., Coffman, R. L. & O'Garra, A. Interleukin-10 and the interleukin-10 receptor. Annu. Rev. Immunol. 19, 683β765 (2001).
Sarangi, P. P., Sehrawat, S., Suvas, S. & Rouse, B. T. IL-10 and natural regulatory T cells: two independent anti-inflammatory mechanisms in herpes simplex virus-induced ocular immunopathology. J. Immunol. 180, 6297β6306 (2008).
Mangia, A. et al. IL-10 haplotypes as possible predictors of spontaneous clearance of HCV infection. Cytokine 25, 103β109 (2004).
Naicker, D. D. et al. Interleukin-10 promoter polymorphisms influence HIV-1 susceptibility and primary HIV-1 pathogenesis. J. Infect. Dis. 200, 448β452 (2009).
Sun, J., Madan, R., Karp, C. L. & Braciale, T. J. Effector T cells control lung inflammation during acute influenza virus infection by producing IL-10. Nature Med. 15, 277β284 (2009). This study showed that by making IL-10, effector CD8+ T cells limit the extent of pulmonary tissue damage.
Elrefaei, M. et al. HIV-specific IL-10-positive CD8+ T cells suppress cytolysis and IL-2 production by CD8+ T cells. J. Immunol. 178, 3265β3271 (2007).
Kobasa, D. et al. Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus. Nature 445, 319β323 (2007).
Li, M. O. & Flavell, R. A. Contextual regulation of inflammation: a duet by transforming growth factor-Ξ² and interleukin-10. Immunity 28, 468β476 (2008).
Li, M. O. & Flavell, R. A. TGF-Ξ²: a master of all T cell trades. Cell 134, 392β404 (2008).
Aung, H., Wu, M., Johnson, J. L., Hirsch, C. S. & Toossi, Z. Bioactivation of latent transforming growth factor Ξ²1 by Mycobacterium tuberculosis in human mononuclear phagocytes. Scand. J. Immunol. 61, 558β565 (2005).
Omer, F. M., de Souza, J. B., Corran, P. H., Sultan, A. A. & Riley, E. M. Activation of transforming growth factor Ξ² by malaria parasite-derived metalloproteinases and a thrombospondin-like molecule. J. Exp. Med. 198, 1817β1827 (2003).
Schultz-Cherry, S. & Hinshaw, V. S. Influenza virus neuraminidase activates latent transforming growth factor Ξ². J. Virol. 70, 8624β8629 (1996).
Beckham, J. D., Tuttle, K. & Tyler, K. L. Reovirus activates transforming growth factor Ξ² and bone morphogenetic protein signaling pathways in the central nervous system that contribute to neuronal survival following infection. J. Virol. 83, 5035β5045 (2009).
Alatrakchi, N. et al. Hepatitis C virus (HCV)-specific CD8+ cells produce transforming growth factor Ξ² that can suppress HCV-specific T-cell responses. J. Virol. 81, 5882β5892 (2007).
Tinoco, R., Alcalde, V., Yang, Y., Sauer, K. & Zuniga, E. I. Cell-intrinsic transforming growth factor-Ξ² signaling mediates virus-specific CD8+ T cell deletion and viral persistence in vivo. Immunity 31, 145β157 (2009). This report showed that TGFΞ² functions intrinsically to limit CD8+T cell responses to viral infection.
O'Connor, W. Jr et al. A protective function for interleukin 17A in T cell-mediated intestinal inflammation. Nature Immunol. 10, 603β609 (2009).
Hou, W., Kang, H. S. & Kim, B. S. Th17 cells enhance viral persistence and inhibit T cell cytotoxicity in a model of chronic virus infection. J. Exp. Med. 206, 313β328 (2009).
Rabinovich, G. A. & Toscano, M. A. Turning 'sweet' on immunity: galectin-glycan interactions in immune tolerance and inflammation. Nature Rev. Immunol. 9, 338β352 (2009).
Zhu, C. et al. The Tim-3 ligand galectin-9 negatively regulates T helper type 1 immunity. Nature Immunol. 6, 1245β1252 (2005).
Sehrawat, S., Suryawanshi, A., Hirashima, M. & Rouse, B. T. Role of Tim-3/galectin-9 inhibitory interaction in viral-induced immunopathology: shifting the balance toward regulators. J. Immunol. 182, 3191β3201 (2009). This paper showed that galectin 9 could promote FOXP3+ T Reg cell responses and that ligation of TIM3 with galectin 9 induces apoptosis of effector T cells but not T Reg cells.
Sehrawat, S., Reddy, P. B. J., Rajasagi, N., Suryawanshi, A., Hirashima, M. & Rouse, B. T. Galectin-9/TIM-3 interaction regulates virus-specific primary and memory CD8+ T cell response. PLoS Pathog. 6, e1000882 (2010).
Chagan-Yasutan, H. et al. Persistent elevation of plasma osteopontin levels in HIV patients despite highly active antiretroviral therapy. Tohoku J. Exp. Med. 218, 285β92 (2009).
Mengshol, J. A. et al. A crucial role for kupffer cell-derived galectin-9 in regulation of T cell immunity in hepatitis C infection. PLoS ONE 5, e9504 (2010).
Sakaguchi, S. Regulatory T cells: key controllers of immunologic self-tolerance. Cell 101, 455β458 (2000).
Belkaid, Y. & Tarbell, K. Regulatory T cells in the control of host-microorganism interactions. Annu. Rev. Immunol. 27, 551β589 (2009).
Suvas, S., Azkur, A. K., Kim, B. S., Kumaraguru, U. & Rouse, B. T. CD4+CD25+ regulatory T cells control the severity of viral immunoinflammatory lesions. J. Immunol. 172, 4123β4132 (2004).
Ruckwardt, T. J., Bonaparte, K. L., Nason, M. C. & Graham, B. S. Regulatory T cells promote early influx of CD8+ T cells in the lungs of respiratory syncytial virus-infected mice and diminish immunodominance disparities. J. Virol. 83, 3019β3028 (2009).
Lanteri, M. C. et al. Tregs control the development of symptomatic West Nile virus infection in humans and mice. J. Clin. Invest. 119, 3266β3277 (2009).
Sehrawat, S., Suvas, S., Sarangi, P. P., Suryawanshi, A. & Rouse, B. T. In vitro-generated antigen-specific CD4+ CD25+ Foxp3+ regulatory T cells control the severity of herpes simplex virus-induced ocular immunoinflammatory lesions. J. Virol. 82, 6838β6851 (2008).
Sehrawat, S. & Rouse, B. T. Anti-inflammatory effects of FTY720 against viral-induced immunopathology: role of drug-induced conversion of T cells to become Foxp3+ regulators. J. Immunol. 180, 7636β7647 (2008).
Rouse, B. T., Sarangi, P. P. & Suvas, S. Regulatory T cells in virus infections. Immunol. Rev. 212, 272β286 (2006).
MacDonald, A. J. et al. CD4 T helper type 1 and regulatory T cells induced against the same epitopes on the core protein in hepatitis C virus-infected persons. J. Infect. Dis. 185, 720β727 (2002). This report showed that induction of T regulatory 1 cells in patients infected with HCV negatively correlated with the extent of liver damage.
Liew, F. Y., Xu, D., Brint, E. K. & O'Neill, L. A. Negative regulation of Toll-like receptor-mediated immune responses. Nature Rev. Immunol. 5, 446β458 (2005).
Virgin, H. W., Wherry, E. J. & Ahmed, R. Redefining chronic viral infection. Cell 138, 30β50 (2009).
Barber, D. L. et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682β687 (2006). This seminal paper showed that the functional T cell exhaustion caused by a chronic viral infection could be reversed using antibody specific for the inhibitory molecule PD1.
Day, C. L. et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350β354 (2006). This report showed that antigen-specific CD8+ T cells isolated from patients with HIV expressed higher levels of the inhibitory molecule PD1 and that the exhaustion could be reversed, at least ex vivo , by using blocking antibody.
Radziewicz, H. et al. Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression. J. Virol. 81, 2545β2553 (2007).
Maier, H., Isogawa, M., Freeman, G. J. & Chisari, F. V. PD-1:PD-L1 interactions contribute to the functional suppression of virus-specific CD8+ T lymphocytes in the liver. J. Immunol. 178, 2714β2720 (2007).
Said, E. A. et al. Programmed death-1-induced interleukin-10 production by monocytes impairs CD4+ T cell activation during HIV infection. Nature Med. 16, 452β459 (2010).
Yao, Z. Q., King, E., Prayther, D., Yin, D. & Moorman, J. T cell dysfunction by hepatitis C virus core protein involves PD-1/PDL-1 signaling. Viral Immunol. 20, 276β287 (2007).
Boasso, A. et al. 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. 129, 132β144 (2008).
Brooks, D. G. et al. IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection. Proc. Natl Acad. Sci. USA 105, 20428β20433 (2008).
Blackburn, S. D. et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nature Immunol. 10, 29β37 (2009).
Brooks, D. G., Lee, A. M., Elsaesser, H., McGavern, D. B. & Oldstone, M. B. IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection. J. Exp. Med. 205, 533β541 (2008).
Ha, S. J. et al. Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. J. Exp. Med. 205, 543β555 (2008).
Racaniello, V. R. One hundred years of poliovirus pathogenesis. Virology 344, 9β16 (2006).
Whitley, R. J. Herpes Simplex Viruses (eds Knipe, D. M & Howley, P. M.) (Lippincott Williams & Wilkins, New York, 2001).
Tabeta, K. et al. The Unc93b1 mutation 3d disrupts exogenous antigen presentation and signaling via Toll-like receptors 3, 7 and 9. Nature Immunol. 7, 156β164 (2006).
Zhang, S. Y. et al. TLR3 deficiency in patients with herpes simplex encephalitis. Science 317, 1522β1527 (2007).
McIntosh, E. D. Paediatric infections: prevention of transmission and disease β implications for adults. Vaccine 23, 2087β2089 (2005).
Rothberg, M. B., Haessler, S. D. & Brown, R. B. Complications of viral influenza. Am. J. Med. 121, 258β264 (2008).
Tregoning, J. S. & Schwarze, J. Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology. Clin. Microbiol Rev. 23, 74β98 (2010).
Collins, P. L. & Graham, B. S. Viral and host factors in human respiratory syncytial virus pathogenesis. J. Virol. 82, 2040β2055 (2008).
Spann, K. M., Tran, K. C., Chi, B., Rabin, R. L. & Collins, P. L. Suppression of the induction of Ξ±, Ξ², and Ξ» interferons by the NS1 and NS2 proteins of human respiratory syncytial virus in human epithelial cells and macrophages. J. Virol. 78, 4363β4369 (2004).
Smit, J. J. et al. The balance between plasmacytoid DC versus conventional DC determines pulmonary immunity to virus infections. PLoS ONE 3, e1720 (2008).
Culley, F. J., Pollott, J. & Openshaw, P. J. Age at first viral infection determines the pattern of T cell-mediated disease during reinfection in adulthood. J. Exp. Med. 196, 1381β1386 (2002). The influence of age at first exposure to a viral infection on the susceptibility of the same infection later in the life was shown in a mouse model of RSV infection.
Whitley, R. J. A 70-year-old woman with shingles: review of herpes zoster. JAMA 302, 73β80 (2009).
Rouse, B. T. & Kaistha, S. D. A tale of 2 alpha-herpesviruses: lessons for vaccinologists. Clin. Infect. Dis. 42, 810β817 (2006).
Nikolich-Zugich, J. Ageing and life-long maintenance of T-cell subsets in the face of latent persistent infections. Nature Rev. Immunol. 8, 512β522 (2008).
Maue, A. C. et al. T-cell immunosenescence: lessons learned from mouse models of aging. Trends Immunol. 30, 301β305 (2009).
Snyder, C. M. et al. Memory inflation during chronic viral infection is maintained by continuous production of short-lived, functional T cells. Immunity 29, 650β659 (2008).
Schakel, K. Dendritic cells β why can they help and hurt us. Exp. Dermatol. 18, 264β273 (2009).
Haaland, R. E. et al. Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog. 5, e1000274 (2009).
McDermott, A. B. et al. Repeated low-dose mucosal simian immunodeficiency virus SIVmac239 challenge results in the same viral and immunological kinetics as high-dose challenge: a model for the evaluation of vaccine efficacy in nonhuman primates. J. Virol. 78, 3140β3144 (2004).
Oh, S., McCaffery, J. M. & Eichelberger, M. C. Dose-dependent changes in influenza virus-infected dendritic cells result in increased allogeneic T-cell proliferation at low, but not high, doses of virus. J. Virol. 74, 5460β5469 (2000).
Legge, K. L. & Braciale, T. J. Lymph node dendritic cells control CD8+ T cell responses through regulated FasL expression. Immunity 23, 649β659 (2005).
Asabe, S. et al. The size of the viral inoculum contributes to the outcome of hepatitis B virus infection. J. Virol. 83, 9652β9662 (2009). This study investigated the influence of dose of infecting HBV on the pathogenesis of liver disease and clearly showed that very high or very low doses of infection led to severe liver damage.
King, N. J. et al. Immunopathology of flavivirus infections. Immunol. Cell Biol. 85, 33β42 (2007).
Wang, T. et al. Toll-like receptor 3 mediates West Nile virus entry into the brain causing lethal encephalitis. Nature Med. 10, 1366β1373 (2004).
Koelle, D. M. & Corey, L. Herpes simplex: insights on pathogenesis and possible vaccines. Annu. Rev. Med. 59, 381β395 (2008).
Weiner, L. P. Pathogenesis of demyelination induced by a mouse hepatitis. Arch. Neurol. 28, 298β303 (1973).
Fazakerley, J. K. & Walker, R. Virus demyelination. J. Neurovirol. 9, 148β164 (2003).
Cole, G. A., Nathanson, N. & Prendergast, R. A. Requirement for ΞΈ-bearing cells in lymphocytic choriomeningitis virus-induced central nervous system disease. Nature 238, 335β337 (1972).
Halstead, S. B. Dengue. Lancet 370, 1644β1652 (2007).
Mathew, A. & Rothman, A. L. Understanding the contribution of cellular immunity to dengue disease pathogenesis. Immunol. Rev. 225, 300β313 (2008).
Hadinoto, V. et al. On the dynamics of acute EBV infection and the pathogenesis of infectious mononucleosis. Blood 111, 1420β1427 (2008).
Clute, S. C. et al. Cross-reactive influenza virus-specific CD8+ T cells contribute to lymphoproliferation in Epstein-Barr virus-associated infectious mononucleosis. J. Clin. Invest. 115, 3602β3612 (2005). This study showed that major contributors to infectious mononucleosis are cross-reactive T cells specific for a previously encountered virus.
Kim, S. K. et al. Private specificities of CD8 T cell responses control patterns of heterologous immunity. J. Exp. Med. 201, 523β533 (2005).
Welsh, R. M. & Fujinami, R. S. Pathogenic epitopes, heterologous immunity and vaccine design. Nature Rev. Microbiol. 5, 555β563 (2007).
Segal, S. & Hill, A. V. Genetic susceptibility to infectious disease. Trends Microbiol. 11, 445β448 (2003).
Goulder, P. J. & Watkins, D. I. Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nature Rev. Immunol. 8, 619β630 (2008).
Brass, A. L. et al. Identification of host proteins required for HIV infection through a functional genomic screen. Science 319, 921β926 (2008).
Good, R. A. & Hansen, M. A. Primary immunodeficiency diseases. Adv. Exp. Med. Biol. 73, 155β178 (1976).
Liu, R. et al. Homozygous defect in HIV-1 coreceptor accounts for resistance of some multiply-exposed individuals to HIV-1 infection. Cell 86, 367β377 (1996).
Hill, A. V. Aspects of genetic susceptibility to human infectious diseases. Annu. Rev. Genet. 40, 469β486 (2006).
Casrouge, A. et al. Herpes simplex virus encephalitis in human UNC-93B deficiency. Science 314, 308β312 (2006).
Zhang, S. Y. et al. Inborn errors of interferon (IFN)-mediated immunity in humans: insights into the respective roles of IFN-Ξ±/Ξ², IFN-Ξ³, and IFN-Ξ» in host defense. Immunol. Rev. 226, 29β40 (2008).
Kaur, G. & Mehra, N. Genetic determinants of HIV-1 infection and progression to AIDS: susceptibility to HIV infection. Tissue Antigens 73, 289β301 (2009).
Hubert, J. B. et al. Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group. AIDS 14, 123β131 (2000). This study showed that some patients with HIV can control the virus for a long time without the need for antiretroviral therapy.
Seifarth, W. et al. Comprehensive analysis of human endogenous retrovirus transcriptional activity in human tissues with a retrovirus-specific microarray. J. Virol. 79, 341β352 (2005).
Lower, R., Lower, J. & Kurth, R. The viruses in all of us: characteristics and biological significance of human endogenous retrovirus sequences. Proc. Natl Acad. Sci. USA 93, 5177β5184 (1996).
Wilkins, C. & Gale, M. Jr. Recognition of viruses by cytoplasmic sensors. Curr. Opin. Immunol. 22, 41β47 (2001).
York, I. A. et al. A cytosolic herpes simplex virus protein inhibits antigen presentation to CD8+ T lymphocytes. Cell 77, 525β535 (1994).
Ahn, K. et al. Human cytomegalovirus inhibits antigen presentation by a sequential multistep process. Proc. Natl Acad. Sci. USA 93, 10990β10995 (1996).
Gilbert, M. J., Riddell, S. R., Plachter, B. & Greenberg, P. D. Cytomegalovirus selectively blocks antigen processing and presentation of its immediate-early gene product. Nature 383, 720β722 (1996).
Levitskaya, J., Sharipo, A., Leonchiks, A., Ciechanover, A. & Masucci, M. G. Inhibition of ubiquitin/proteasome-dependent protein degradation by the Gly-Ala repeat domain of the Epstein-Barr virus nuclear antigen 1. Proc. Natl Acad. Sci. USA 94, 12616β12621 (1997).
Koppelman, B., Neefjes, J. J., de Vries, J. E. & de Waal Malefyt, R. Interleukin-10 down-regulates MHC class II Ξ±Ξ² peptide complexes at the plasma membrane of monocytes by affecting arrival and recycling. Immunity 7, 861β871 (1997).
Greenberg, M. E. et al. Co-localization of HIV-1 Nef with the AP-2 adaptor protein complex correlates with Nef-induced CD4 down-regulation. EMBO J. 16, 6964β6976 (1997).
Holmes, E. C. Evolutionary history and phylogeography of human viruses. Annu. Rev. Microbiol. 62, 307β328 (2008).
Devergne, O., Birkenbach, M. & Kieff, E. EpsteinβBarr virus-induced gene 3 and the p35 subunit of interleukin 12 form a novel heterodimeric hematopoietin. Proc. Natl Acad. Sci. USA 94, 12041β12046 (1997).
Moskophidis, D., Lechner, F., Pircher, H. & Zinkernagel, R. M. Virus persistence in acutely infected immunocompetent mice by exhaustion of antiviral cytotoxic effector T cells. Nature 362, 758β761 (1993).
Periwal, S. B. & Cebra, J. J. Respiratory mucosal immunization with reovirus serotype 1/L stimulates virus-specific humoral and cellular immune responses, including double-positive (CD4+/CD8+) T cells. J. Virol. 73, 7633β7640 (1999).
Fulton, J. R., Smith, J., Cunningham, C. & Cuff, C. F. Influence of the route of infection on development of T-cell receptor Ξ²-chain repertoires of reovirus-specific cytotoxic T lymphocytes. J. Virol. 78, 1582β1590 (2004).
Le Goffic, R. et al. Detrimental contribution of the Toll-like receptor (TLR)3 to influenza A virus-induced acute pneumonia. PLoS Pathog. 2, e53 (2006).
Bochud, P. Y., Magaret, A. S., Koelle, D. M., Aderem, A. & Wald, A. Polymorphisms in TLR2 are associated with increased viral shedding and lesional rate in patients with genital herpes simplex virus type 2 infection. J. Infect. Dis. 196, 505β509 (2007).
Almarri, A. & Batchelor, J. R. HLA and hepatitis B infection. Lancet 344, 1194β1195 (1994).
Gao, X. et al. AIDS restriction HLA allotypes target distinct intervals of HIV-1 pathogenesis. Nature Med. 11, 1290β1292 (2005).
Fellay, J. et al. A whole-genome association study of major determinants for host control of HIV-1. Science 317, 944β947 (2007).
Fanning, L. J. et al. HLA class II genes determine the natural variance of hepatitis C viral load. Hepatology 33, 224β230 (2001).
Thomas, D. L. et al. Genetic variation in IL28B and spontaneous clearance of hepatitis C virus. Nature 461, 798β801 (2009).
Ge, D. et al. Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance. Nature 461, 399β401 (2009).
Knapp, S. et al. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection: roles of MxA, OAS-1 and PKR. Genes Immun. 4, 411β419 (2003).
Monto, A. S. Epidemiology of influenza. Vaccine 26, D45βD48 (2008).
Peebles, R. S. Jr & Graham, B. S. Pathogenesis of respiratory syncytial virus infection in the murine model. Proc. Am. Thorac Soc. 2, 110β115 (2005).
Lemke, G. & Rothlin, C. V. Immunobiology of the TAM receptors. Nature Rev. Immunol. 8, 327β336 (2008).
Acknowledgements
We thank D. Masopust and M. Sangster for valuable comments. The work was supported by US National Institutes of Health grants RO1 AI 106336501 and RO1 EY 05093.
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- Plasmacytoid DC
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A dendritic cell (DC) subset with a morphology that resembles that of a plasmablast. Plasmacytoid DCs produce large amounts of type I interferons in response to viral infection.
- Resolvins
-
Resolution-phase interaction products that are made by the host from eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and that have anti-inflammatory properties.
- Galectins
-
A family of lectin proteins that bind a wide variety of glycoproteins and glycolipids containing Ξ²-galactosides through their carbohydrate-recognition domain. They have extracellular and intracellular functions, including the regulation of apoptosis, RAS signalling, cell adhesion and angiogenesis.
- Regulatory T (TReg) cells
-
A subset of T cells that control the activity of effector T cells under inflammatory or steady state conditions.
- Protectins
-
A family of compounds that are derived from DHA and that are characterized by a conjugated triene-containing structure. They have been shown to regulate the influx of neutrophils at inflammatory sites.
- Exhaustion
-
Impaired ability of effector T cells to carry out their functions such as cytotoxicity and cytokine secretion owing to chronic stimulation by antigen.
- Latent infection
-
A dormant infection with a microorganism that persists in the body for a long period of time, but it can be reactivated under certain conditions, such as immunosuppression.
- Shingles
-
A viral disease characterized by painful, blistering skin rashes due to infection or recurrence of infection with varicella zoster virus.
- Innate receptors
-
The receptors that are present either on the surface or in the cytoplasm of innate immune cells that recognize microbial surface patterns or their replicative products and induce cytokine production.
- Dengue haemorrhagic fever
-
A viral disease transmitted by the bites of Aedes egypti mosquitos that carry dengue virus and is characterized by headache, fever, rash and evidence of haemorrhage in the body.
- Infectious mononucleosis
-
A viral disease caused by infection with EpsteinβBarr virus most commonly during adolescence and young adulthood. The classical symptoms include fever, sore throat and swollen lymph glands, especially in the neck.
- Virome
-
The total virus-derived genetic material present in the host owing to integrated or persistent exogenous viruses.
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Rouse, B., Sehrawat, S. Immunity and immunopathology to viruses: what decides the outcome?. Nat Rev Immunol 10, 514β526 (2010). https://doi.org/10.1038/nri2802
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DOI: https://doi.org/10.1038/nri2802
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