An Overview of HMGB1 and its Potential Role as a Biomarker for RSV Infection

Author(s): Sara Manti*, Caterina Cuppari, Giuseppe Fabio Parisi, Carmelo Salpietro.

Journal Name: Current Respiratory Medicine Reviews

Volume 15 , Issue 3 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Respiratory Syncytial Virus (RSV), an enveloped, non-segmented, negative-sense RNA virus of the Paramyxoviridae family, is the most common respiratory pathogen in infants and young children worldwide, also leading to lower respiratory tract infections during infancy and subsequent development of recurrent wheezing and asthma in childhood. Despite many years of research, we still lack reliable biomarkers of the disease activity as well as effective vaccines and therapeutic strategies. Recent studies have directed attention toward High Mobility Group Box-1 (HMGB1), a 30 kDa nuclear and cytosolic ubiquitous protein, belonging to the alarmins family and promoting an immediate activation of the innate immune response, as a biomarker potentially able to elucidate the link between the RSV and chronic airway dysfunction. Herein, we aimed to summarize what is known on RSV-HMGB1 link, also describing recent findings coming from our experimental studies.

Keywords: Bronchiolitis, children, HMGB1, infectious diseases, respiratory syncytial virus, lower respiratory tract infections.

[1]
Geoghegan S, Erviti A, Caballero MT, et al. Mortality due to respiratory syncytial virus. burden and risk factors. Am J Respir Crit Care Med 2017; 195(1): 96-103.
[http://dx.doi.org/10.1164/rccm.201603-0658OC] [PMID: 27331632]
[2]
Hall CB, Weinberg GA, Iwane MK, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med 2009; 360(6): 588-98.
[http://dx.doi.org/10.1056/NEJMoa0804877] [PMID: 19196675]
[3]
McClure DL, Kieke BA, Sundaram ME, et al. Seasonal incidence of medically attended respiratory syncytial virus infection in a community cohort of adults ≥50 years old. PLoS One 2014; 9(7)e102586
[http://dx.doi.org/10.1371/journal.pone.0102586] [PMID: 25025344]
[4]
Manti S, Cuppari C, Lanzafame A, et al. Detection of respiratory syncytial virus (RSV) at birth in a newborn with respiratory distress. Pediatr Pulmonol 2017; 52(10): E81-4.
[http://dx.doi.org/10.1002/ppul.23775] [PMID: 28834426]
[5]
Piedimonte G. RSV infections: State of the art. Cleve Clin J Med 2015; 82(11)(Suppl. 1): S13-8.
[http://dx.doi.org/10.3949/ccjm.82.s1.03] [PMID: 26555808]
[6]
Singleton RJ, Redding GJ, Lewis TC, et al. Sequelae of severe respiratory syncytial virus infection in infancy and early childhood among Alaska Native children. Pediatrics 2003; 112(2): 285-90.
[http://dx.doi.org/10.1542/peds.112.2.285] [PMID: 12897275]
[7]
Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Björkstén B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics 1995; 95(4): 500-5.
[PMID: 7700748]
[8]
Stein RT, Sherrill D, Morgan WJ, et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet 1999; 354(9178): 541-5.
[http://dx.doi.org/10.1016/S0140-6736(98)10321-5] [PMID: 10470697]
[9]
Sigurs N, Aljassim F, Kjellman B, et al. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. Thorax 2010; 65(12): 1045-52.
[http://dx.doi.org/10.1136/thx.2009.121582] [PMID: 20581410]
[10]
Korppi M, Piippo-Savolainen E, Korhonen K, Remes S. Respiratory morbidity 20 years after RSV infection in infancy. Pediatr Pulmonol 2004; 38(2): 155-60.
[http://dx.doi.org/10.1002/ppul.20058] [PMID: 15211700]
[11]
Escobar GJ, Ragins A, Li SX, Prager L, Masaquel AS, Kipnis P. Recurrent wheezing in the third year of life among children born at 32 weeks’ gestation or later: relationship to laboratory-confirmed, medically attended infection with respiratory syncytial virus during the first year of life. Arch Pediatr Adolesc Med 2010; 164(10): 915-22.
[http://dx.doi.org/10.1001/archpediatrics.2010.177] [PMID: 20921348]
[12]
Storch GA, Anderson LJ, Park CS, Tsou C, Dohner DE. Antigenic and genomic diversity within group A respiratory syncytial virus. J Infect Dis 1991; 163(4): 858-61.
[http://dx.doi.org/10.1093/infdis/163.4.858] [PMID: 2010638]
[13]
Openshaw PJ, Yamaguchi Y, Tregoning JS. Childhood infections, the developing immune system, and the origins of asthma. J Allergy Clin Immunol 2004; 114(6): 1275-7.
[http://dx.doi.org/10.1016/j.jaci.2004.08.024] [PMID: 15577822]
[14]
Janssen R, Bont L, Siezen CL, et al. Genetic susceptibility to respiratory syncytial virus bronchiolitis is predominantly associated with innate immune genes. J Infect Dis 2007; 196(6): 826-34.
[http://dx.doi.org/10.1086/520886] [PMID: 17703412]
[15]
Martinez FD, Stern DA, Wright AL, Taussig LM, Halonen M. Differential immune responses to acute lower respiratory illness in early life and subsequent development of persistent wheezing and asthma. J Allergy Clin Immunol 1998; 102(6 Pt 1): 915-20.
[http://dx.doi.org/10.1016/S0091-6749(98)70328-8] [PMID: 9847431]
[16]
Tortorolo L, Langer A, Polidori G, et al. Neurotrophin overexpression in lower airways of infants with respiratory syncytial virus infection. Am J Respir Crit Care Med 2005; 172(2): 233-7.
[http://dx.doi.org/10.1164/rccm.200412-1693OC] [PMID: 15879412]
[17]
Manti S, Brown P, Perez MK, Piedimonte G. The role of neurotrophins in inflammation and allergy. Vitam Horm 2017; 104: 313-41.
[http://dx.doi.org/10.1016/bs.vh.2016.10.010] [PMID: 28215300]
[18]
Castleman WL, Sorkness RL, Lemanske RF, Grasee G, Suyemoto MM. Neonatal viral bronchiolitis and pneumonia induces bronchiolar hypoplasia and alveolar dysplasia in rats. Lab Invest 1988; 59(3): 387-96.
[PMID: 3411939]
[19]
Blount RE Jr, Morris JA, Savage RE. Recovery of cytopathogenic agent from chimpanzees with coryza. Proc Soc Exp Biol Med 1956; 92(3): 544-9.
[http://dx.doi.org/10.3181/00379727-92-22538] [PMID: 13359460]
[20]
Hosakote YM, Brasier AR, Casola A, Garofalo RP, Kurosky A. Respiratory syncytial virus infection triggers epithelial HMGB1 release as a damage-associated molecular pattern promoting a monocytic inflammatory response. J Virol 2016; 90(21): 9618-31.
[http://dx.doi.org/10.1128/JVI.01279-16] [PMID: 27535058]
[21]
Hou CC, Zhao HJ, Cai SX, Li WJ, Tong WC, Liu LY. [Respiratory syncytial virus increases the expression and release of high mobility group Box-1 protein in the lung tissue of mice]. Nan Fang Yi Ke Da Xue Xue Bao 2010; 30(4): 700-3.
[PMID: 20423829]
[22]
Harris HE, Raucci A. Alarmin(g) news about danger: workshop on innate danger signals and HMGB1. EMBO Rep 2006; 7(8): 774-8.
[http://dx.doi.org/10.1038/sj.embor.7400759] [PMID: 16858429]
[23]
Chirico V, Lacquaniti A, Vinci S, et al. High-mobility group box 1 in allergic and non allergic upper airway inflammation. J Biol Regul Homeost Agents 2015; 29(2)(Suppl. 1): 55-7.
[PMID: 26634588]
[24]
Yang H, Wang H, Chavan SS, Andersson U. High mobility group box protein 1 (HMGB1): The prototypical endogenous danger molecule. Mol Med 2015; 21(Suppl. 1): S6-S12.
[http://dx.doi.org/10.2119/molmed.2015.00087] [PMID: 26605648]
[25]
Javaherian K, Sadeghi M, Liu LF. Nonhistone proteins HMG1 and HMG2 unwind DNA double helix. Nucleic Acids Res 1979; 6(11): 3569-80.
[http://dx.doi.org/10.1093/nar/6.11.3569] [PMID: 226939]
[26]
Bustin M, Neihart NK. Antibodies against chromosomal HMG proteins stain the cytoplasm of mammalian cells. Cell 1979; 16(1): 181-9.
[http://dx.doi.org/10.1016/0092-8674(79)90199-5] [PMID: 369705]
[27]
Rovere-Querini P, Capobianco A, Scaffidi P, et al. HMGB1 is an endogenous immune adjuvant released by necrotic cells. EMBO Rep 2004; 5(8): 825-30.
[http://dx.doi.org/10.1038/sj.embor.7400205] [PMID: 15272298]
[28]
Gallucci S, Matzinger P. Danger signals: SOS to the immune system. Curr Opin Immunol 2001; 13(1): 114-9.
[http://dx.doi.org/10.1016/S0952-7915(00)00191-6] [PMID: 11154927]
[29]
Yu M, Wang H, Ding A, et al. HMGB1 signals through toll-like receptor (TLR) 4 and TLR2. Shock 2006; 26(2): 174-9.
[http://dx.doi.org/10.1097/01.shk.0000225404.51320.82] [PMID: 16878026]
[30]
Luo Y, Li SJ, Yang J, Qiu YZ, Chen FP. HMGB1 induces an inflammatory response in endothelial cells via the RAGE-dependent endoplasmic reticulum stress pathway. Biochem Biophys Res Commun 2013; 438(4): 732-8.
[http://dx.doi.org/10.1016/j.bbrc.2013.07.098] [PMID: 23911608]
[31]
Pistoia V, Raffaghello L. Damage-associated Molecular Patterns (DAMPs) and mesenchymal stem cells: a matter of attraction and excitement. Eur J Immunol 2011; 41(7): 1828-31.
[http://dx.doi.org/10.1002/eji.201141724] [PMID: 21706488]
[32]
Frank MG, Weber MD, Watkins LR, Maier SF. Stress sounds the alarmin: The role of the danger-associated molecular pattern HMGB1 in stress-induced neuroinflammatory priming. Brain Behav Immun 2015; 48: 1-7.
[http://dx.doi.org/10.1016/j.bbi.2015.03.010] [PMID: 25816800]
[33]
Kang R, Chen R, Zhang Q, et al. HMGB1 in health and disease. Mol Aspects Med 2014; 40: 1-116.
[http://dx.doi.org/10.1016/j.mam.2014.05.001] [PMID: 25010388]
[34]
Salpietro C, Cuppari C, Grasso L, et al. Nasal high-mobility group box-1 protein in children with allergic rhinitis. Int Arch Allergy Immunol 2013; 161(2): 116-21.
[http://dx.doi.org/10.1159/000345246] [PMID: 23343652]
[35]
Cavone L, Cuppari C, Manti S, et al. Increase in the level of proinflammatory cytokine HMGB1 in nasal fluids of patients with rhinitis and its sequestration by glycyrrhizin induces eosinophil cell death. Clin Exp Otorhinolaryngol 2015; 8(2): 123-8.
[http://dx.doi.org/10.3342/ceo.2015.8.2.123] [PMID: 26045910]
[36]
Manti S, Leonardi S, Parisi GF, et al. High mobility group box 1: Biomarker of inhaled corticosteroid treatment response in children with moderate-severe asthma. Allergy Asthma Proc 2017; 38(3): 197-203.
[http://dx.doi.org/10.2500/aap.2017.38.4047] [PMID: 28441990]
[37]
Manti S, Cuppari C, Tardino L, et al. HMGB1 as a new biomarker of celiac disease in children: A multicenter study. Nutrition 2017; 37: 18-21.
[http://dx.doi.org/10.1016/j.nut.2016.12.011] [PMID: 28359357]
[38]
Cuppari C, Manti S, Salpietro A, et al. HMGB1 levels in children with atopic eczema/dermatitis syndrome (AEDS). Pediatr Allergy Immunol 2016; 27(1): 99-102.
[http://dx.doi.org/10.1111/pai.12481] [PMID: 26388323]
[39]
Cuppari C, Manti S, Chirico V, et al. Sputum high mobility group box-1 in asthmatic children: A noninvasive sensitive biomarker reflecting disease status. Ann Allergy Asthma Immunol 2015; 115(2): 103-7.
[http://dx.doi.org/10.1016/j.anai.2015.06.008] [PMID: 26250770]
[40]
Moisy D, Avilov SV, Jacob Y, et al. HMGB1 protein binds to influenza virus nucleoprotein and promotes viral replication. J Virol 2012; 86(17): 9122-33.
[http://dx.doi.org/10.1128/JVI.00789-12] [PMID: 22696656]
[41]
Song MJS, Hwang S, Wong W, et al. The DNA architectural protein HMGB1 facilitates RTA-mediated viral gene expression in gamma-2 herpesviruses. J Virol 2004; 78(23): 12940-50.
[http://dx.doi.org/10.1128/JVI.78.23.12940-12950.2004] [PMID: 15542646]
[42]
Costello E, Saudan P, Winocour E, Pizer L, Beard P. High mobility group chromosomal protein 1 binds to the adeno-associated virus replication protein (Rep) and promotes Rep-mediated site-specific cleavage of DNA, ATPase activity and transcriptional repression. EMBO J 1997; 16(19): 5943-54.
[http://dx.doi.org/10.1093/emboj/16.19.5943] [PMID: 9312052]
[43]
Zhu X, Sun L, Wang Y. High mobility group box 1 (HMGB1) is upregulated by the Epstein-Barr virus infection and promotes the proliferation of human nasopharyngeal carcinoma cells. Acta Otolaryngol 2016; 136(1): 87-94.
[http://dx.doi.org/10.3109/00016489.2015.1082192] [PMID: 26382001]
[44]
Cotmore SF, Tattersall P. High-mobility group 1/2 proteins are essential for initiating rolling-circle-type DNA replication at a parvovirus hairpin origin. J Virol 1998; 72(11): 8477-84.
[PMID: 9765384]
[45]
van Zoelen MA, van der Sluijs KF, Achouiti A, et al. Receptor for advanced glycation end products is detrimental during influenza A virus pneumonia. Virology 2009; 391(2): 265-73.
[http://dx.doi.org/10.1016/j.virol.2009.05.032] [PMID: 19592063]
[46]
Ito Y, Torii Y, Ohta R, et al. Increased levels of cytokines and high-mobility group box 1 are associated with the development of severe pneumonia, but not acute encephalopathy, in 2009 H1N1 influenza-infected children. Cytokine 2011; 56(2): 180-7.
[http://dx.doi.org/10.1016/j.cyto.2011.07.016] [PMID: 21862344]
[47]
Nowak P, Barqasho B, Treutiger CJ, et al. HMGB1 activates replication of latent HIV-1 in a monocytic cell-line, but inhibits HIV-1 replication in primary macrophages. Cytokine 2006; 34(1-2): 17-23.
[http://dx.doi.org/10.1016/j.cyto.2006.03.010] [PMID: 16697213]
[48]
Jung JH, Park JH, Jee MH, et al. Hepatitis C virus infection is blocked by HMGB1 released from virus-infected cells. J Virol 2011; 85(18): 9359-68.
[http://dx.doi.org/10.1128/JVI.00682-11] [PMID: 21752923]
[49]
Mukherjee RM, Shravanti GV, Jakkampudi A, et al. Reduced expression of DNA damage repair genes high mobility group box1 and poly(ADP-ribose) polymerase1 in inactive carriers of hepatitis b virus infection-a possible stage of viral integration. J Clin Exp Hepatol 2013; 3(2): 89-95.
[http://dx.doi.org/10.1016/j.jceh.2013.04.003] [PMID: 25755481]
[50]
Allonso D, Belgrano FS, Calzada N, Guzmán MG, Vázquez S, Mohana-Borges R. Elevated serum levels of high mobility group box 1 (HMGB1) protein in dengue-infected patients are associated with disease symptoms and secondary infection. J Clin Virol 2012; 55(3): 214-9.
[http://dx.doi.org/10.1016/j.jcv.2012.07.010] [PMID: 22884669]
[51]
Manti S, Cuppari C, Parisi GF, Tardino L, Salpietro C, Leonardi S. HMGB1 values and response to HBV vaccine in children with celiac disease. Nutrition 2017; 42: 20-2.
[http://dx.doi.org/10.1016/j.nut.2017.05.012] [PMID: 28870474]
[52]
Arrigo T, Leonardi S, Cuppari C, et al. Role of the diet as a link between oxidative stress and liver diseases. World J Gastroenterol 2015; 21(2): 384-95.
[http://dx.doi.org/10.3748/wjg.v21.i2.384] [PMID: 25593454]
[53]
Hosakote Y, Garofalo R, Kurosky A. Respiratory syncytial virus infection triggers HMGB1 release from lung epithelial cells to promote inflammatory cytokine production. J Immunol 2015; 194(1)(Suppl.): 48-9.
[54]
D’Angelo G, Granese R, Marseglia L, et al. High mobility group box 1 and markers of oxidative stress in human cord blood. Pediatr Int (Roma) 2019; 61(3): 264-70.
[http://dx.doi.org/10.1111/ped.13795] [PMID: 30715770]
[55]
D’Angelo G, Marseglia L, Granese R, et al. Different concentration of human cord blood HMGB1 according to delivery and labour: A pilot study. Cytokine 2018; 108: 53-6.
[http://dx.doi.org/10.1016/j.cyto.2018.03.019] [PMID: 29571040]
[56]
Schlegel CR, Ivanciuc T, Garofalo RP, et al. Release of high-mobility group box-1 (HMGB1) in the airways of children with viral lower respiratory tract infections. JACI 2015; 135: 2.
[http://dx.doi.org/10.1016/j.jaci.2014.12.1686]
[57]
Patel MC, Shirey KA, Boukhvalova MS, et al. Serum high-mobility-group box 1 as a biomarker and a therapeutic target during respiratory virus infections. MBio 2018; 9(2)
[58]
Manti S, Harford TJ, Salpietro C, Rezaee F, Piedimonte G. Induction of high-mobility group Box-1 in vitro and in vivo by respiratory syncytial virus. Pediatr Res 2018; 83(5): 1049-56.
[http://dx.doi.org/10.1038/pr.2018.6] [PMID: 29329282]
[59]
Zeng R, Cui Y, Hai Y, Liu Y. Pattern recognition receptors for respiratory syncytial virus infection and design of vaccines. Virus Res 2012; 167(2): 138-45.
[http://dx.doi.org/10.1016/j.virusres.2012.06.003] [PMID: 22698878]
[60]
Chan JK, Roth J, Oppenheim JJ, et al. Alarmins: awaiting a clinical response. J Clin Invest 2012; 122(8): 2711-9.
[http://dx.doi.org/10.1172/JCI62423] [PMID: 22850880]
[61]
Wang H, Bloom O, Zhang M, et al. HMG-1 as a late mediator of endotoxin lethality in mice. Science 1999; 285(5425): 248-51.
[http://dx.doi.org/10.1126/science.285.5425.248] [PMID: 10398600]
[62]
Ploeger B, Mensinga T, Sips A, Seinen W, Meulenbelt J, DeJongh J. The pharmacokinetics of glycyrrhizic acid evaluated by physiologically based pharmacokinetic modeling. Drug Metab Rev 2001; 33(2): 125-47.
[http://dx.doi.org/10.1081/DMR-100104400] [PMID: 11495500]
[63]
Fiore C, Eisenhut M, Krausse R, et al. Antiviral effects of Glycyrrhiza species. Phytother Res 2008; 22(2): 141-8.
[http://dx.doi.org/10.1002/ptr.2295] [PMID: 17886224]
[64]
Matsumoto Y, Matsuura T, Aoyagi H, et al. Antiviral activity of glycyrrhizin against hepatitis C virus in vitro. PLoS One 2013; 8(7)e68992
[http://dx.doi.org/10.1371/journal.pone.0068992] [PMID: 23874843]
[65]
Vispute S, Khopade A. Glycyrrhiza Glabra Linn. - “Klitaka”: A Review. Int J Pharma Bio Sci 2011; 2: 3.
[66]
Zhou JA, Schweinle JE, Lichenstein R, Walker RE, King JC. Severe illnesses associated with outbreaks of respiratory syncytial virus and influenza in adults. Clin Infect Dis 2019. ciz264
[http://dx.doi.org/10.1093/cid/ciz264] [PMID: 30944930]
[67]
Shi T, Denouel A, Tietjen AK, et al. Global disease burden estimates of respiratory syncytial virus-associated acute respiratory infection in older adults in 2015: A systematic review and meta-analysis. J Infect Dis 2019. jiz059
[http://dx.doi.org/10.1093/infdis/jiz059] [PMID: 30880339]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 3
Year: 2019
Page: [205 - 209]
Pages: 5
DOI: 10.2174/1573398X15666190603121448

Article Metrics

PDF: 13
HTML: 2

Special-new-year-discount