{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T11:10:19Z","timestamp":1789384219600,"version":"build-2803163510"},"reference-count":46,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2017,10,22]],"date-time":"2017-10-22T00:00:00Z","timestamp":1508630400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["P30GM110760"],"award-info":[{"award-number":["P30GM110760"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005640","name":"Flight Attendant Medical Research Institute","doi-asserted-by":"publisher","award":["140082"],"award-info":[{"award-number":["140082"]}],"id":[{"id":"10.13039\/100005640","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human Metapneumovirus (HMPV) is a leading respiratory pathogen that causes lower respiratory tract infections worldwide. Acute HMPV infection induces an exacerbated inflammatory neutrophilic response leading to bronchiolitis and pneumonia. However, the mechanism by which the virus regulates neutrophil infiltration into the airways still remains unexplored. In this work, we used an experimental mouse model of HMPV infection to demonstrate that the attachment (G) protein of HMPV contributes to the recruitment of neutrophils into the airways and modulate the production of neutrophil chemoattractants and Type I IFN responses, specifically IFN-\u03b1. These findings provide the first evidence that the HMPV G protein contributes to the in vivo neutrophilic response to HMPV infection and furthers our understanding on virus induced inflammatory responses in the airways.<\/jats:p>","DOI":"10.3390\/v9100310","type":"journal-article","created":{"date-parts":[[2017,10,23]],"date-time":"2017-10-23T04:32:19Z","timestamp":1508733139000},"page":"310","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Human Metapneumovirus Attachment Protein Contributes to Neutrophil Recruitment into the Airways of Infected Mice"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8860-2457","authenticated-orcid":false,"given":"Nagarjuna","family":"Cheemarla","sequence":"first","affiliation":[{"name":"Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-2563","authenticated-orcid":false,"given":"Antonieta","family":"Guerrero-Plata","sequence":"additional","affiliation":[{"name":"Department of Pathobiological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA"},{"name":"Center for Experimental Infectious Disease Research; Louisiana State University, Baton Rouge, LA 70803, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,10,22]]},"reference":[{"key":"ref_1","first-page":"1601","article-title":"Respiratory syncytial virus and metapneumovirus","volume":"Volume 2","author":"Knipe","year":"2007","journal-title":"Fileds Virology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1038\/89098","article-title":"A newly discovered human pneu movirus isolated from young children with respiratory tract disease","volume":"7","author":"Groen","year":"2001","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.jcv.2011.10.002","article-title":"Ten years of human metapneumovirus research","volume":"53","author":"Feuillet","year":"2012","journal-title":"J. Clin. Virol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"634","DOI":"10.3201\/eid0906.030017","article-title":"Human metapneumovirus infections in hospitalized children","volume":"9","author":"Boivin","year":"2003","journal-title":"Emerg. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1097\/INF.0b013e318162a164","article-title":"Human metapneumovirus infection in young children hospitalized with acute respiratory tract disease: Virologic and clinical features","volume":"27","author":"Caracciolo","year":"2008","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"S215","DOI":"10.1097\/01.inf.0000144668.81573.6d","article-title":"Human metapneumovirus as a major cause of human respiratory tract disease","volume":"23","author":"Crowe","year":"2004","journal-title":"Pediatr. Infect. Dis. J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1128\/CMR.00014-06","article-title":"Epidemiology of human metapneumovirus","volume":"19","author":"Kahn","year":"2006","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1056\/NEJMoa025472","article-title":"Human metapneumovirus and lower respiratory tract disease in otherwise healthy infants and children","volume":"350","author":"Williams","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"700","DOI":"10.3201\/eid1004.030555","article-title":"Human metapneumovirus infection among children hospitalized with acute respiratory illness","volume":"10","author":"Mullins","year":"2004","journal-title":"Emerg. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1571","DOI":"10.1086\/379200","article-title":"Prevalence and clinical symptoms of human metapneumovirus infection in hospitalized patients","volume":"188","author":"Fockens","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1086\/367901","article-title":"Human metapneumovirus infections in young and elderly adults","volume":"187","author":"Falsey","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1001\/archinte.168.22.2489","article-title":"Human metapneumovirus infections in adults: Another piece of the puzzle","volume":"168","author":"Walsh","year":"2008","journal-title":"Arch. Int. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.1086\/444392","article-title":"Human metapneumovirus infection plays an etiologic role in acute asthma exacerbations requiring hospitalization in adults","volume":"192","author":"Williams","year":"2005","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1093\/infdis\/jis309","article-title":"Rates of hospitalizations for respiratory syncytial virus, human metapneumovirus, and influenza virus in older adults","volume":"206","author":"Widmer","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"267","DOI":"10.3892\/mmr.2011.416","article-title":"Detection of human metapneumovirus in infants with acute respiratory tract infection","volume":"4","author":"Mammas","year":"2011","journal-title":"Mol. Med. Rep."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Malmo, J., Moe, N., Krokstad, S., Ryan, L., Loevenich, S., Johnsen, I.B., Espevik, T., Nordbo, S.A., Dollner, H., and Anthonsen, M.W. (2016). Cytokine profiles in human metapneumovirus infected children: Identification of genes involved in the antiviral response and pathogenesis. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0155484"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1002\/ppul.23514","article-title":"Neutrophil infiltration and activation in bronchiolitic airways are independent of viral etiology","volume":"52","author":"Cavallaro","year":"2017","journal-title":"Pediatr. Pulmonol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8560","DOI":"10.1128\/JVI.00699-08","article-title":"T lymphocytes contribute to antiviral immunity and pathogenesis in experimental human metapneumovirus infection","volume":"82","author":"Kolli","year":"2008","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8894","DOI":"10.1128\/JVI.79.14.8894-8903.2005","article-title":"Pathogenesis of human metapneumovirus lung infection in balb\/c mice and cotton rats","volume":"79","author":"Hamelin","year":"2005","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Cheemarla, N.R., Banos-Lara, M.D., Naidu, S., and Guerrero-Plata, A. (2017). Neutrophils regulate the lung inflammatory response via \u03b3\u0394 T cell infiltration in an experimental mouse model of human metapneumovirus infection. J. Leukoc. Biol.","DOI":"10.1189\/jlb.4A1216-519RR"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3323","DOI":"10.1128\/JVI.02198-08","article-title":"Age-associated aggravation of clinical disease after primary metapneumovirus infection of balb\/c mice","volume":"83","author":"Darniot","year":"2009","journal-title":"J. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1084\/jem.20132183","article-title":"Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection","volume":"211","author":"Stock","year":"2014","journal-title":"J. Exp. Med."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Seo, S.U., Kwon, H.J., Ko, H.J., Byun, Y.H., Seong, B.L., Uematsu, S., Akira, S., and Kweon, M.N. (2011). Type I interferon signaling regulates Ly6C(HI) monocytes and neutrophils during acute viral pneumonia in mice. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1001304"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/j.cellimm.2011.11.008","article-title":"Type I interferon signaling regulates the composition of inflammatory infiltrates upon infection with listeria monocytogenes","volume":"273","author":"Hoth","year":"2012","journal-title":"Cell. Immunol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1002\/ijc.29945","article-title":"Type I IFNs induce anti-tumor polarization of tumor associated neutrophils in mice and human","volume":"138","author":"Andzinski","year":"2016","journal-title":"Int. J. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.1002\/ijc.28551","article-title":"Cxcr2-mediated tumor-associated neutrophil recruitment is regulated by IFN-\u03b2","volume":"134","author":"Jablonska","year":"2014","journal-title":"Int. J. Cancer"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10190","DOI":"10.1128\/JVI.79.16.10190-10199.2005","article-title":"Activity and regulation of \u03b1 interferon in respiratory syncytial virus and human metapneumovirus experimental infections","volume":"79","author":"Baron","year":"2005","journal-title":"J. Virol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1128\/JVI.02897-14","article-title":"Impact and regulation of \u03bb interferon response in human metapneumovirus infection","volume":"89","author":"Harvey","year":"2015","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Bao, X., Liu, T., Shan, Y., Li, K., Garofalo, R.P., and Casola, A. (2008). Human metapneumovirus glycoprotein g inhibits innate immune responses. PLoS Pathog., 4.","DOI":"10.1371\/journal.ppat.1000077"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Chakraborty, K., Zhou, Z., Wakamatsu, N., and Guerrero-Plata, A. (2012). Interleukin-12p40 modulates human metapneumovirus-induced pulmonary disease in an acute mouse model of infection. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037173"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1007\/978-1-4419-1601-3_4","article-title":"Modulation of innate immune signalling pathways by viral proteins","volume":"666","author":"Mulhern","year":"2009","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1038\/nri2377","article-title":"Innate immune modulation by RNA viruses: Emerging insights from functional genomics","volume":"8","author":"Katze","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"6849","DOI":"10.1128\/JVI.02323-08","article-title":"The Ns1 protein of a human influenza virus inhibits type I interferon production and the induction of antiviral responses in primary human dendritic and respiratory epithelial cells","volume":"83","author":"Haye","year":"2009","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Kitagawa, Y., Sakai, M., Funayama, M., Itoh, M., and Gotoh, B. (2017). Human metapneumovirus M2-2 protein acts as a negative regulator of \u03b1 interferon production by plasmacytoid dendritic cells. J. Virol.","DOI":"10.1128\/JVI.00579-17"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4071","DOI":"10.1128\/JVI.01365-10","article-title":"Both nonstructural proteins Ns1 and Ns2 of pneumonia virus of mice are inhibitors of the interferon type I and type III responses in vivo","volume":"85","author":"Heinze","year":"2011","journal-title":"J. Virol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1910","DOI":"10.1172\/JCI35412","article-title":"Type I IFNs mediate development of postinfluenza bacterial pneumonia in mice","volume":"119","author":"Shahangian","year":"2009","journal-title":"J. Clin. Investig."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Bonville, C.A., Percopo, C.M., Dyer, K.D., Gao, J., Prussin, C., Foster, B., Rosenberg, H.F., and Domachowske, J.B. (2009). Interferon-gamma coordinates Ccl3-mediated neutrophil recruitment In Vivo. BMC Immunol., 10.","DOI":"10.1186\/1471-2172-10-14"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"10070","DOI":"10.1128\/JVI.01347-13","article-title":"The respiratory syncytial virus fusion protein and neutrophils mediate the airway mucin response to pathogenic respiratory syncytial virus infection","volume":"87","author":"Stokes","year":"2013","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Vidy, A., Maisonnasse, P., Da Costa, B., Delmas, B., Chevalier, C., and Le Goffic, R. (2016). The influenza virus protein Pb1-F2 increases viral pathogenesis through neutrophil recruitment and Nk cells inhibition. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165361"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"6287","DOI":"10.4049\/jimmunol.1200385","article-title":"IL-17 and TNF-\u03b1 sustain neutrophil recruitment during inflammation through synergistic effects on endothelial activation","volume":"188","author":"Griffin","year":"2012","journal-title":"J. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1084\/jem.20051725","article-title":"Twist mediates suppression of inflammation by type I IFNs and Axl","volume":"203","author":"Sharif","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Cui, F., Meng, J., Luo, P., and Chen, P. (2014). IFN-\u03b1 blocks IL-17 production by peripheral blood mononuclear cells in patients with chronic active hepatitis b infection. BMC Infect. Dis., 14.","DOI":"10.1186\/1471-2334-14-55"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4653","DOI":"10.1182\/blood-2012-04-421040","article-title":"VEGF-A recruits a proangiogenic MMP-9-delivering neutrophil subset that induces angiogenesis in transplanted hypoxic tissue","volume":"120","author":"Christoffersson","year":"2012","journal-title":"Blood"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1093\/jnci\/95.6.437","article-title":"Effects of interferon alpha on vascular endothelial growth factor gene transcription and tumor angiogenesis","volume":"95","author":"Scholz","year":"2003","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Wang, C.J., Xiao, C.W., You, T.G., Zheng, Y.X., Gao, W., Zhou, Z.Q., Chen, J., Xue, X.B., Fan, J., and Zhang, H. (2012). Interferon-\u03b1 enhances antitumor activities of oncolytic adenovirus-mediated IL-24 expression in hepatocellular carcinoma. Mol. Cancer, 11.","DOI":"10.1186\/1476-4598-11-31"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1016\/j.immuni.2010.07.018","article-title":"Lipid-cytokine-chemokine cascade drives neutrophil recruitment in a murine model of inflammatory arthritis","volume":"33","author":"Chou","year":"2010","journal-title":"Immunity"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/9\/10\/310\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:48:07Z","timestamp":1760208487000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/9\/10\/310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,10,22]]},"references-count":46,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2017,10]]}},"alternative-id":["v9100310"],"URL":"https:\/\/doi.org\/10.3390\/v9100310","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,10,22]]}}}