The role of myeloid cell activation and arginine metabolism in the pathogenesis of virus-induced diseases

Kristina S Burrack, Thomas E Morrison, Kristina S Burrack, Thomas E Morrison

Abstract

WHEN AN ANTIVIRAL IMMUNE RESPONSE IS GENERATED, A BALANCE MUST BE REACHED BETWEEN TWO OPPOSING PATHWAYS: the production of proinflammatory and cytotoxic effectors that drive a robust antiviral immune response to control the infection and regulators that function to limit or blunt an excessive immune response to minimize immune-mediated pathology and repair tissue damage. Myeloid cells, including monocytes and macrophages, play an important role in this balance, particularly through the activities of the arginine-hydrolyzing enzymes nitric oxide synthase 2 (Nos2; iNOS) and arginase 1 (Arg1). Nitric oxide (NO) production by iNOS is an important proinflammatory mediator, whereas Arg1-expressing macrophages contribute to the resolution of inflammation and wound repair. In the context of viral infections, expression of these enzymes can result in a variety of outcomes for the host. NO has direct antiviral properties against some viruses, whereas during other virus infections NO can mediate immunopathology and/or inhibit the antiviral immune response to promote chronic infection. Arg1 activity not only has important wound healing functions but can also inhibit the antiviral immune response during some viral infections. Thus, depending on the specific virus and the tissue(s) involved, the activity of both of these arginine-hydrolyzing enzymes can either exacerbate or limit the severity of virus-induced disease. In this review, we will discuss a variety of viral infections, including HIV, SARS-CoV, LCMV, HCV, RSV, and others, where myeloid cells influence the control and clearance of the virus from the host, as well as the severity and resolution of tissue damage, via the activities of iNOS and/or Arg1. Clearly, monocyte/macrophage activation and arginine metabolism will continue to be important areas of investigation in the context of viral infections.

Keywords: arginase; cellular; iNOS; immunity; macrophages; viral pathogenicity.

References

    1. Murray PJ, Wynn TA. Protective and pathogenic functions of macrophage subsets. Nat Rev Immunol (2011) 11(11):723–3710.1038/nri3073
    1. Mills CD. M1 and M2 macrophages: oracles of health and disease. Crit Rev Immunol (2012) 32(6):463–8810.1615/CritRevImmunol.v32.i6.10
    1. Munder M. Arginase: an emerging key player in the mammalian immune system. Br J Pharmacol (2009) 158(3):638–5110.1111/j.1476-5381.2009.00291.x
    1. Gabrilovich DI, Ostrand-Rosenberg S, Bronte V. Coordinated regulation of myeloid cells by tumours. Nat Rev Immunol (2012) 12(4):253–6810.1038/nri3175
    1. Kong YY, Fuchsberger M, Xiang SD, Apostolopoulos V, Plebanski M. Myeloid derived suppressor cells and their role in diseases. Curr Med Chem (2013) 20(11):1437–4410.2174/0929867311320110006
    1. Murray PJ, Allen JE, Biswas SK, Fisher EA, Gilroy DW, Goerdt S, et al. Macrophage activation and polarization: nomenclature and experimental guidelines. Immunity (2014) 41(1):14–2010.1016/j.immuni.2014.06.008
    1. Nathan CF, Hibbs JB., Jr Role of nitric oxide synthesis in macrophage antimicrobial activity. Curr Opin Immunol (1991) 3(1):65–7010.1016/0952-7915(91)90079-G
    1. James SL. Role of nitric oxide in parasitic infections. Microbiol Rev (1995) 59(4):533–47
    1. Karupiah G, Xie QW, Buller RM, Nathan C, Duarte C, MacMicking JD. Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. Science (1993) 261(5127):1445–810.1126/science.7690156
    1. Croen KD. Evidence for antiviral effect of nitric oxide. Inhibition of herpes simplex virus type 1 replication. J Clin Invest (1993) 91(6):2446–5210.1172/JCI116479
    1. Bi Z, Reiss CS. Inhibition of vesicular stomatitis virus infection by nitric oxide. J Virol (1995) 69(4):2208–13
    1. Lin YL, Huang YL, Ma SH, Yeh CT, Chiou SY, Chen LK, et al. Inhibition of Japanese encephalitis virus infection by nitric oxide: antiviral effect of nitric oxide on RNA virus replication. J Virol (1997) 71(7):5227–35
    1. Neves-Souza PC, Azeredo EL, Zagne SM, Valls-de-Souza R, Reis SR, Cerqueira DI, et al. Inducible nitric oxide synthase (iNOS) expression in monocytes during acute dengue fever in patients and during in vitro infection. BMC Infect Dis (2005) 5:64.10.1186/1471-2334-5-64
    1. Zaragoza C, Ocampo C, Saura M, Leppo M, Wei XQ, Quick R, et al. The role of inducible nitric oxide synthase in the host response to coxsackievirus myocarditis. Proc Natl Acad Sci U S A (1998) 95(5):2469–7410.1073/pnas.95.5.2469
    1. Zaragoza C, Ocampo CJ, Saura M, Bao C, Leppo M, Lafond-Walker A, et al. Inducible nitric oxide synthase protection against coxsackievirus pancreatitis. J Immunol (1999) 163(10):5497–504
    1. Flodstrom M, Horwitz MS, Maday A, Balakrishna D, Rodriguez E, Sarvetnick N. A critical role for inducible nitric oxide synthase in host survival following coxsackievirus B4 infection. Virology (2001) 281(2):205–1510.1006/viro.2000.0801
    1. Lowenstein CJ, Hill SL, Lafond-Walker A, Wu J, Allen G, Landavere M, et al. Nitric oxide inhibits viral replication in murine myocarditis. J Clin Invest (1996) 97(8):1837–4310.1172/JCI118613
    1. Karupiah G, Chen JH, Nathan CF, Mahalingam S, MacMicking JD. Identification of nitric oxide synthase 2 as an innate resistance locus against ectromelia virus infection. J Virol (1998) 72(9):7703–6
    1. Shirey KA, Pletneva LM, Puche AC, Keegan AD, Prince GA, Blanco JC, et al. Control of RSV-induced lung injury by alternatively activated macrophages is IL-4R alpha-, TLR4-, and IFN-beta-dependent. Mucosal Immunol (2010) 3(3):291–30010.1038/mi.2010.6
    1. Shirey KA, Lai W, Pletneva LM, Karp CL, Divanovic S, Blanco JC, et al. Role of the lipoxygenase pathway in RSV-induced alternatively activated macrophages leading to resolution of lung pathology. Mucosal Immunol (2013) 7(3):549–5710.1038/mi.2013.71
    1. Shirey KA, Lai W, Pletneva LM, Finkelman FD, Feola DJ, Blanco JC, et al. Agents that increase AAM differentiation blunt RSV-mediated lung pathology. J Leukoc Biol (2014).10.1189/jlb.4HI0414-226R
    1. Kodukula P, Liu T, Rooijen NV, Jager MJ, Hendricks RL. Macrophage control of herpes simplex virus type 1 replication in the peripheral nervous system. J Immunol (1999) 162(5):2895–905
    1. van Den Broek M, Bachmann MF, Kohler G, Barner M, Escher R, Zinkernagel R, et al. IL-4 and IL-10 antagonize IL-12-mediated protection against acute vaccinia virus infection with a limited role of IFN-gamma and nitric oxide synthetase 2. J Immunol (2000) 164(1):371–810.4049/jimmunol.164.1.371
    1. Conrady CD, Zheng M, Mandal NA, van Rooijen N, Carr DJ. IFN-alpha-driven CCL2 production recruits inflammatory monocytes to infection site in mice. Mucosal Immunol (2013) 6(1):45–5510.1038/mi.2012.46
    1. Zolini GP, Lima GK, Lucinda N, Silva MA, Dias MF, Pessoa NL, et al. Defense against HSV-1 in a murine model is mediated by iNOS and orchestrated by the activation of TLR2 and TLR9 in trigeminal ganglia. J Neuroinflammation (2014) 11:20.10.1186/1742-2094-11-20
    1. MacLean A, Wei XQ, Huang FP, Al-Alem UA, Chan WL, Liew FY. Mice lacking inducible nitric-oxide synthase are more susceptible to herpes simplex virus infection despite enhanced Th1 cell responses. J Gen Virol (1998) 79(Pt 4):825–30
    1. Wang J, Li F, Sun R, Gao X, Wei H, Li LJ, et al. Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages. Nat Commun (2013) 4:2106.10.1038/ncomms3106
    1. Bodaghi B, Goureau O, Zipeto D, Laurent L, Virelizier JL, Michelson S. Role of IFN-gamma-induced indoleamine 2,3 dioxygenase and inducible nitric oxide synthase in the replication of human cytomegalovirus in retinal pigment epithelial cells. J Immunol (1999) 162(2):957–64
    1. Noda S, Tanaka K, Sawamura S, Sasaki M, Matsumoto T, Mikami K, et al. Role of nitric oxide synthase type 2 in acute infection with murine cytomegalovirus. J Immunol (2001) 166(5):3533–4110.4049/jimmunol.166.5.3533
    1. Li K, Xu W, Guo Q, Jiang Z, Wang P, Yue Y, et al. Differential macrophage polarization in male and female BALB/c mice infected with coxsackievirus B3 defines susceptibility to viral myocarditis. Circ Res (2009) 105(4):353–6410.1161/CIRCRESAHA.109.195230
    1. Liu W, Moussawi M, Roberts B, Boyson JE, Huber SA. Cross-regulation of T regulatory-cell response after coxsackievirus B3 infection by NKT and gammadelta T cells in the mouse. Am J Pathol (2013) 183(2):441–910.1016/j.ajpath.2013.04.015
    1. Harris N, Buller RM, Karupiah G. Gamma interferon-induced, nitric oxide-mediated inhibition of vaccinia virus replication. J Virol (1995) 69(2):910–5
    1. Djeraba A, Bernardet N, Dambrine G, Quere P. Nitric oxide inhibits Marek’s disease virus replication but is not the single decisive factor in interferon-gamma-mediated viral inhibition. Virology (2000) 277(1):58–6510.1006/viro.2000.0576
    1. Xing Z, Schat KA. Inhibitory effects of nitric oxide and gamma interferon on in vitro and in vivo replication of Marek’s disease virus. J Virol (2000) 74(8):3605–1210.1128/JVI.74.8.3605-3612.2000
    1. Djeraba A, Musset E, van Rooijen N, Quere P. Resistance and susceptibility to Marek’s disease: nitric oxide synthase/arginase activity balance. Vet Microbiol (2002) 86(3):229–4410.1016/S0378-1135(02)00010-X
    1. Guidotti LG, McClary H, Loudis JM, Chisari FV. Nitric oxide inhibits hepatitis B virus replication in the livers of transgenic mice. J Exp Med (2000) 191(7):1247–5210.1084/jem.191.7.1247
    1. Valero N, Espina LM, Anez G, Torres E, Mosquera JA. Short report: increased level of serum nitric oxide in patients with dengue. Am J Trop Med Hyg (2002) 66(6):762–4
    1. Fagundes CT, Costa VV, Cisalpino D, Amaral FA, Souza PR, Souza RS, et al. IFN-gamma production depends on IL-12 and IL-18 combined action and mediates host resistance to dengue virus infection in a nitric oxide-dependent manner. PLoS Negl Trop Dis (2011) 5(12):e1449.10.1371/journal.pntd.0001449
    1. Costa VV, Fagundes CT, Valadao DF, Cisalpino D, Dias AC, Silveira KD, et al. A model of DENV-3 infection that recapitulates severe disease and highlights the importance of IFN-gamma in host resistance to infection. PLoS Negl Trop Dis (2012) 6(5):e1663.10.1371/journal.pntd.0001663
    1. Mendes-Ribeiro AC, Moss MB, Siqueira MA, Moraes TL, Ellory JC, Mann GE, et al. Dengue fever activates the l-arginine-nitric oxide pathway: an explanation for reduced aggregation of human platelets. Clin Exp Pharmacol Physiol (2008) 35(10):1143–610.1111/j.1440-1681.2008.04970.x
    1. Achike FI. The l-arginine-nitric oxide pathway: a potential therapeutic target in dengue haemorrhagic fever. Clin Exp Pharmacol Physiol (2008) 35(10):1135–610.1111/j.1440-1681.2008.05022.x
    1. Getts DR, Terry RL, Getts MT, Muller M, Rana S, Deffrasnes C, et al. Targeted blockade in lethal West Nile virus encephalitis indicates a crucial role for very late antigen (VLA)-4-dependent recruitment of nitric oxide-producing macrophages. J Neuroinflammation (2012) 9:246.10.1186/1742-2094-9-246
    1. Tucker PC, Griffin DE, Choi S, Bui N, Wesselingh S. Inhibition of nitric oxide synthesis increases mortality in Sindbis virus encephalitis. J Virol (1996) 70(6):3972–7
    1. Goody RJ, Hoyt CC, Tyler KL. Reovirus infection of the CNS enhances iNOS expression in areas of virus-induced injury. Exp Neurol (2005) 195(2):379–9010.1016/j.expneurol.2005.05.016
    1. Rimmelzwaan GF, Baars MM, de Lijster P, Fouchier RA, Osterhaus AD. Inhibition of influenza virus replication by nitric oxide. J Virol (1999) 73(10):8880–3
    1. Darwish I, Miller C, Kain KC, Liles WC. Inhaled nitric oxide therapy fails to improve outcome in experimental severe influenza. Int J Med Sci (2012) 9(2):157–6210.7150/ijms.3880
    1. Burggraaf S, Bingham J, Payne J, Kimpton WG, Lowenthal JW, Bean AG. Increased inducible nitric oxide synthase expression in organs is associated with a higher severity of H5N1 influenza virus infection. PLoS One (2011) 6(1):e14561.10.1371/journal.pone.0014561
    1. Akaike T, Noguchi Y, Ijiri S, Setoguchi K, Suga M, Zheng YM, et al. Pathogenesis of influenza virus-induced pneumonia: involvement of both nitric oxide and oxygen radicals. Proc Natl Acad Sci U S A (1996) 93(6):2448–5310.1073/pnas.93.6.2448
    1. Karupiah G, Chen JH, Mahalingam S, Nathan CF, MacMicking JD. Rapid interferon gamma-dependent clearance of influenza A virus and protection from consolidating pneumonitis in nitric oxide synthase 2-deficient mice. J Exp Med (1998) 188(8):1541–610.1084/jem.188.8.1541
    1. Jayasekera JP, Vinuesa CG, Karupiah G, King NJ. Enhanced antiviral antibody secretion and attenuated immunopathology during influenza virus infection in nitric oxide synthase-2-deficient mice. J Gen Virol (2006) 87(Pt 11):3361–7110.1099/vir.0.82131-0
    1. Perrone LA, Belser JA, Wadford DA, Katz JM, Tumpey TM. Inducible nitric oxide contributes to viral pathogenesis following highly pathogenic influenza virus infection in mice. J Infect Dis (2013) 207(10):1576–8410.1093/infdis/jit062
    1. Mgbemena V, Segovia JA, Chang TH, Tsai SY, Cole GT, Hung CY, et al. Transactivation of inducible nitric oxide synthase gene by Kruppel-like factor 6 regulates apoptosis during influenza A virus infection. J Immunol (2012) 189(2):606–1510.4049/jimmunol.1102742
    1. Lin KL, Suzuki Y, Nakano H, Ramsburg E, Gunn MD. CCR2+ monocyte-derived dendritic cells and exudate macrophages produce influenza-induced pulmonary immune pathology and mortality. J Immunol (2008) 180(4):2562–7210.4049/jimmunol.180.4.2562
    1. Aldridge JR, Jr, Moseley CE, Boltz DA, Negovetich NJ, Reynolds C, Franks J, et al. TNF/iNOS-producing dendritic cells are the necessary evil of lethal influenza virus infection. Proc Natl Acad Sci U S A (2009) 106(13):5306–1110.1073/pnas.0900655106
    1. Konturek PC, Brzozowski T, Kania J, Konturek SJ, Kwiecien S, Pajdo R, et al. Pioglitazone, a specific ligand of peroxisome proliferator-activated receptor-gamma, accelerates gastric ulcer healing in rat. Eur J Pharmacol (2003) 472(3):213–2010.1016/S0014-2999(03)01932-0
    1. Zhao J, Van Rooijen N, Perlman S. Evasion by stealth: inefficient immune activation underlies poor T cell response and severe disease in SARS-CoV-infected mice. PLoS Pathog (2009) 5(10):e1000636.10.1371/journal.ppat.1000636
    1. Page C, Goicochea L, Matthews K, Zhang Y, Klover P, Holtzman MJ, et al. Induction of alternatively activated macrophages enhances pathogenesis during severe acute respiratory syndrome coronavirus infection. J Virol (2012) 86(24):13334–4910.1128/JVI.01689-12
    1. Adler H, Beland JL, Del-Pan NC, Kobzik L, Brewer JP, Martin TR, et al. Suppression of herpes simplex virus type 1 (HSV-1)-induced pneumonia in mice by inhibition of inducible nitric oxide synthase (iNOS, NOS2). J Exp Med (1997) 185(9):1533–4010.1084/jem.185.9.1533
    1. Gamba G, Cavalieri H, Courreges MC, Massouh EJ, Benencia F. Early inhibition of nitric oxide production increases HSV-1 intranasal infection. J Med Virol (2004) 73(2):313–2210.1002/jmv.20093
    1. Marques CP, Cheeran MC, Palmquist JM, Hu S, Lokensgard JR. Microglia are the major cellular source of inducible nitric oxide synthase during experimental herpes encephalitis. J Neurovirol (2008) 14(3):229–3810.1080/13550280802093927
    1. Mora AL, Torres-Gonzalez E, Rojas M, Corredor C, Ritzenthaler J, Xu J, et al. Activation of alveolar macrophages via the alternative pathway in herpesvirus-induced lung fibrosis. Am J Respir Cell Mol Biol (2006) 35(4):466–7310.1165/rcmb.2006-0121OC
    1. Dutia BM, Clarke CJ, Allen DJ, Nash AA. Pathological changes in the spleens of gamma interferon receptor-deficient mice infected with murine gammaherpesvirus: a role for CD8 T cells. J Virol (1997) 71(6):4278–83
    1. Ebrahimi B, Dutia BM, Brownstein DG, Nash AA. Murine gammaherpesvirus-68 infection causes multi-organ fibrosis and alters leukocyte trafficking in interferon-gamma receptor knockout mice. Am J Pathol (2001) 158(6):2117–2510.1016/S0002-9440(10)64683-4
    1. Zhu Y, Jones G, Tsutsui S, Opii W, Liu S, Silva C, et al. Lentivirus infection causes neuroinflammation and neuronal injury in dorsal root ganglia: pathogenic effects of STAT-1 and inducible nitric oxide synthase. J Immunol (2005) 175(2):1118–2610.4049/jimmunol.175.2.1118
    1. Green KA, Cook WJ, Green WR. Myeloid-derived suppressor cells in murine retrovirus-induced AIDS inhibit T- and B-cell responses in vitro that are used to define the immunodeficiency. J Virol (2013) 87(4):2058–7110.1128/JVI.01547-12
    1. Daley-Bauer LP, Wynn GM, Mocarski ES. Cytomegalovirus impairs antiviral CD8+ T cell immunity by recruiting inflammatory monocytes. Immunity (2012) 37(1):122–3310.1016/j.immuni.2012.04.014
    1. Wilson EB, Kidani Y, Elsaesser H, Barnard J, Raff L, Karp CL, et al. Emergence of distinct multiarmed immunoregulatory antigen-presenting cells during persistent viral infection. Cell Host Microbe (2012) 11(5):481–9110.1016/j.chom.2012.03.009
    1. Trujillo JA, Fleming EL, Perlman S. Transgenic CCL2 expression in the central nervous system results in a dysregulated immune response and enhanced lethality after coronavirus infection. J Virol (2013) 87(5):2376–8910.1128/JVI.03089-12
    1. Stoermer KA, Burrack A, Oko L, Montgomery SA, Borst LB, Gill RG, et al. Genetic ablation of arginase 1 in macrophages and neutrophils enhances clearance of an arthritogenic alphavirus. J Immunol (2012) 189(8):4047–5910.4049/jimmunol.1201240
    1. Norris BA, Uebelhoer LS, Nakaya HI, Price AA, Grakoui A, Pulendran B. Chronic but not acute virus infection induces sustained expansion of myeloid suppressor cell numbers that inhibit viral-specific T cell immunity. Immunity (2013) 38(2):309–2110.1016/j.immuni.2012.10.022
    1. Cao W, Sun B, Feitelson MA, Wu T, Tur-Kaspa R, Fan Q. Hepatitis C virus targets over-expression of arginase I in hepatocarcinogenesis. Int J Cancer (2009) 124(12):2886–9210.1002/ijc.24265
    1. Fischer-Smith T, Tedaldi EM, Rappaport J. CD163/CD16 coexpression by circulating monocytes/macrophages in HIV: potential biomarkers for HIV infection and AIDS progression. AIDS Res Hum Retroviruses (2008) 24(3):417–2110.1089/aid.2007.0193
    1. Qin A, Cai W, Pan T, Wu K, Yang Q, Wang N, et al. Expansion of monocytic myeloid-derived suppressor cells dampens T cell function in HIV-1-seropositive individuals. J Virol (2013) 87(3):1477–9010.1128/JVI.01759-12
    1. Cloke TE, Garvey L, Choi BS, Abebe T, Hailu A, Hancock M, et al. Increased level of arginase activity correlates with disease severity in HIV-seropositive patients. J Infect Dis (2010) 202(3):374–8510.1086/653736
    1. Cloke TE, Abebe T, Hailu A, Munder M, Taylor GP, Muller I, et al. Antiretroviral therapy abrogates association between arginase activity and HIV disease severity. Trans R Soc Trop Med Hyg (2010) 104(11):746–810.1016/j.trstmh.2010.08.004
    1. Garg A, Spector SA. HIV type 1 gp120-induced expansion of myeloid derived suppressor cells is dependent on interleukin 6 and suppresses immunity. J Infect Dis (2014) 209(3):441–5110.1093/infdis/jit469
    1. Takele Y, Abebe T, Weldegebreal T, Hailu A, Hailu W, Hurissa Z, et al. Arginase activity in the blood of patients with visceral leishmaniasis and HIV infection. PLoS Negl Trop Dis (2013) 7(1):e1977.10.1371/journal.pntd.0001977
    1. Bility MT, Cheng L, Zhang Z, Luan Y, Li F, Chi L, et al. Hepatitis B virus infection and immunopathogenesis in a humanized mouse model: induction of human-specific liver fibrosis and M2-like macrophages. PLoS Pathog (2014) 10(3):e1004032.10.1371/journal.ppat.1004032
    1. Sandalova E, Laccabue D, Boni C, Watanabe T, Tan A, Zong HZ, et al. Increased levels of arginase in patients with acute hepatitis B suppress antiviral T cells. Gastroenterology (2012) 143(1): 78–87.e3.10.1053/j.gastro.2012.03.041
    1. Das A, Hoare M, Davies N, Lopes AR, Dunn C, Kennedy PT, et al. Functional skewing of the global CD8 T cell population in chronic hepatitis B virus infection. J Exp Med (2008) 205(9):2111–2410.1084/jem.20072076
    1. De Santo C, Salio M, Masri SH, Lee LY, Dong T, Speak AO, et al. Invariant NKT cells reduce the immunosuppressive activity of influenza A virus-induced myeloid-derived suppressor cells in mice and humans. J Clin Invest (2008) 118(12):4036–4810.1172/JCI36264
    1. Long JP, Kotur MS, Stark GV, Warren RL, Kasoji M, Craft JL, et al. Accumulation of CD11b(+)Gr-1(+) cells in the lung, blood and bone marrow of mice infected with highly pathogenic H5N1 and H1N1 influenza viruses. Arch Virol (2013) 158(6):1305–2210.1007/s00705-012-1593-3
    1. Osborne LC, Monticelli LA, Nice TJ, Sutherland TE, Siracusa MC, Hepworth HR, et al. Virus-helminth coinfection reveals a microbiota-independent mechanism of immunomodulation. Science (2014) 345(6196):578–8210.1126/science.1256942
    1. Stamler JS, Singel DJ, Loscalzo J. Biochemistry of nitric oxide and its redox-activated forms. Science (1992) 258(5090):1898–90210.1126/science.1281928
    1. Lepoivre M, Chenais B, Yapo A, Lemaire G, Thelander L, Tenu JP. Alterations of ribonucleotide reductase activity following induction of the nitrite-generating pathway in adenocarcinoma cells. J Biol Chem (1990) 265(24):14143–9
    1. Kwon NS, Stuehr DJ, Nathan CF. Inhibition of tumor cell ribonucleotide reductase by macrophage-derived nitric oxide. J Exp Med (1991) 174(4):761–710.1084/jem.174.4.761
    1. Wink DA, Kasprzak KS, Maragos CM, Elespuru RK, Misra M, Dunams TM, et al. DNA deaminating ability and genotoxicity of nitric oxide and its progenitors. Science (1991) 254(5034):1001–310.1126/science.1948068
    1. Nguyen T, Brunson D, Crespi CL, Penman BW, Wishnok JS, Tannenbaum SR. DNA damage and mutation in human cells exposed to nitric oxide in vitro. Proc Natl Acad Sci U S A (1992) 89(7):3030–410.1073/pnas.89.7.3030
    1. Goldstein DJ, Weller SK. Factor(s) present in herpes simplex virus type 1-infected cells can compensate for the loss of the large subunit of the viral ribonucleotide reductase: characterization of an ICP6 deletion mutant. Virology (1988) 166(1):41–5110.1016/0042-6822(88)90144-4
    1. Jacobson JG, Leib DA, Goldstein DJ, Bogard CL, Schaffer PA, Weller SK, et al. A herpes simplex virus ribonucleotide reductase deletion mutant is defective for productive acute and reactivatable latent infections of mice and for replication in mouse cells. Virology (1989) 173(1):276–8310.1016/0042-6822(89)90244-4
    1. Zell R, Markgraf R, Schmidtke M, Gorlach M, Stelzner A, Henke A, et al. Nitric oxide donors inhibit the coxsackievirus B3 proteinases 2A and 3C in vitro, virus production in cells, and signs of myocarditis in virus-infected mice. Med Microbiol Immunol (2004) 193(2–3):91–10010.1007/s00430-003-0198-6
    1. Mills CD. Molecular basis of “suppressor” macrophages. Arginine metabolism via the nitric oxide synthetase pathway. J Immunol (1991) 146(8):2719–23
    1. Ahmed R, Salmi A, Butler LD, Chiller JM, Oldstone MB. Selection of genetic variants of lymphocytic choriomeningitis virus in spleens of persistently infected mice. Role in suppression of cytotoxic T lymphocyte response and viral persistence. J Exp Med (1984) 160(2):521–4010.1084/jem.160.2.521
    1. Butz EA, Bevan MJ. Massive expansion of antigen-specific CD8+ T cells during an acute virus infection. Immunity (1998) 8(2):167–7510.1016/S1074-7613(00)80469-0
    1. Wherry EJ, Blattman JN, Murali-Krishna K, van der Most R, Ahmed R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J Virol (2003) 77(8):4911–2710.1128/JVI.77.8.4911-4927.2003
    1. Richter K, Perriard G, Behrendt R, Schwendener RA, Sexl V, Dunn R, et al. Macrophage and T cell produced IL-10 promotes viral chronicity. PLoS Pathog (2013) 9(11):e1003735.10.1371/journal.ppat.1003735
    1. Bowen JL, Olson JK. Innate immune CD11b+Gr-1+ cells, suppressor cells, affect the immune response during Theiler’s virus-induced demyelinating disease. J Immunol (2009) 183(11):6971–8010.4049/jimmunol.0902193
    1. Cai W, Qin A, Guo P, Yan D, Hu F, Yang Q, et al. Clinical significance and functional studies of myeloid-derived suppressor cells in chronic hepatitis C patients. J Clin Immunol (2013) 33(4):798–80810.1007/s10875-012-9861-2
    1. Tacke RS, Lee HC, Goh C, Courtney J, Polyak SJ, Rosen HR, et al. Myeloid suppressor cells induced by hepatitis C virus suppress T-cell responses through the production of reactive oxygen species. Hepatology (2012) 55(2):343–5310.1002/hep.24700
    1. Cassol E, Cassetta L, Alfano M, Poli G. Macrophage polarization and HIV-1 infection. J Leukoc Biol (2010) 87(4):599–60810.1189/jlb.1009673
    1. Lawn SD, Butera ST, Folks TM. Contribution of immune activation to the pathogenesis and transmission of human immunodeficiency virus type 1 infection. Clin Microbiol Rev (2001) 14(4):753–7710.1128/CMR.14.4.753-777.2001
    1. Liaw YF, Chu CM. Hepatitis B virus infection. Lancet (2009) 373(9663):582–9210.1016/S0140-6736(09)60207-5
    1. Lepique AP, Daghastanli KR, Cuccovia IM, Villa LL. HPV16 tumor associated macrophages suppress antitumor T cell responses. Clin Cancer Res (2009) 15(13):4391–40010.1158/1078-0432.CCR-09-0489
    1. Goh C, Narayanan S, Hahn YS. Myeloid-derived suppressor cells: the dark knight or the joker in viral infections? Immunol Rev (2013) 255(1):210–2110.1111/imr.12084
    1. Gangadharan B, Hoeve MA, Allen JE, Ebrahimi B, Rhind SM, Dutia BM, et al. Murine gammaherpesvirus-induced fibrosis is associated with the development of alternatively activated macrophages. J Leukoc Biol (2008) 84(1):50–810.1189/jlb.0507270

Source: PubMed

Sponsorer og samarbeidspartnere

Medisinsk tilstand

Legemiddelintervensjoner

3
Abonnere