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Soluble extracellular proteins, including immunoglobulins, blood clotting factors, proteins of the complement system, and\/or antimicrobial peptides (AMPs) can exert direct effects by binding to a virus capsid that modifies interactions with pattern recognition receptors and downstream signaling. In addition, the presence, generation, or secretion of extracellular proteins can indirectly influence the response to HAdVs via the activation and recruitment of cells at the site of infection.<\/jats:p>","DOI":"10.3390\/v12121351","type":"journal-article","created":{"date-parts":[[2020,11,26]],"date-time":"2020-11-26T09:04:15Z","timestamp":1606381455000},"page":"1351","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Adenovirus\u2014Extracellular Protein Interactions and Their Impact on Innate Immune Responses by Human Mononuclear Phagocytes"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2503-9174","authenticated-orcid":false,"given":"Coraline","family":"Ch\u00e9neau","sequence":"first","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier, Universit\u00e9 de Montpellier, CNRS (French National Centre for Scientific Research), 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6114-7530","authenticated-orcid":false,"given":"Eric J.","family":"Kremer","sequence":"additional","affiliation":[{"name":"Institut de G\u00e9n\u00e9tique Mol\u00e9culaire de Montpellier, Universit\u00e9 de Montpellier, CNRS (French National Centre for Scientific Research), 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,26]]},"reference":[{"key":"ref_1","unstructured":"Harrach, B., and Benk\u0151, M. (2020). Adenoviridae. Encyclopedia of Virology, Elsevier. Chapter 00057."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3660","DOI":"10.1002\/1873-3468.13687","article-title":"Adenoviruses across the animal kingdom: A walk in the zoo","volume":"593","author":"Harrach","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.gendis.2017.04.001","article-title":"Adenovirus-mediated gene delivery: Potential applications for gene and cell-based therapies in the new era of personalized medicine","volume":"4","author":"Lee","year":"2017","journal-title":"Genes Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1128\/CMR.00116-13","article-title":"Adenovirus Infections in Immunocompetent and Immunocompromised Patients","volume":"27","author":"Lion","year":"2014","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.ebiom.2017.12.030","article-title":"Intestinal Adenovirus Shedding Before Allogeneic Stem Cell Transplantation Is a Risk Factor for Invasive Infection Post-transplant","volume":"28","author":"Kosulin","year":"2018","journal-title":"EBioMedicine"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Collins, N.D., Adhikari, A., Yang, Y., Kuschner, R.A., Karasavvas, N., Binn, L.N., Walls, S.D., Graf, P.C.F., Myers, C.A., and Jarman, R.G. (2020). Live Oral Adenovirus Type 4 and Type 7 Vaccine Induces Durable Antibody Response. Vaccines, 8.","DOI":"10.3390\/vaccines8030411"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"772","DOI":"10.1093\/infdis\/jiw244","article-title":"Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S\/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP","volume":"214","author":"Rampling","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1080\/15376510802312464","article-title":"Biodistribution and Toxicological Safety of Adenovirus Type 5 and Type 35 Vectored Vaccines Against Human Immunodeficiency Virus-1 (HIV-1), Ebola, or Marburg Are Similar Despite Differing Adenovirus Serotype Vector, Manufacturer\u2019s Construct, or Gene Inserts","volume":"5","author":"Sheets","year":"2008","journal-title":"J. Immunotoxicol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/S0140-6736(20)31604-4","article-title":"Safety and immunogenicity of the ChAdOx1 nCoV-19 vaccine against SARS-CoV-2: A preliminary report of a phase 1\/2, single-blind, randomised controlled trial","volume":"396","author":"Folegatti","year":"2020","journal-title":"Lancet"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/s41586-020-2607-z","article-title":"Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques","volume":"586","author":"Mercado","year":"2020","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1080\/14760584.2019.1698952","article-title":"Ebola vaccine trials: Progress in vaccine safety and immunogenicity","volume":"18","author":"Matz","year":"2019","journal-title":"Expert Rev. Vaccines"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ymthe.2020.10.002","article-title":"Pros and Cons of Adenovirus-Based SARS-CoV-2 Vaccines","volume":"28","author":"Kremer","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2717","DOI":"10.1084\/jem.20081786","article-title":"Activation of a dendritic cell\u2013T cell axis by Ad5 immune complexes creates an improved environment for replication of HIV in T cells","volume":"205","author":"Perreau","year":"2008","journal-title":"J. Exp. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1128\/JVI.01265-10","article-title":"Adenovirus membrane penetration activates the NLRP3 inflammasome","volume":"85","author":"Barlan","year":"2011","journal-title":"J. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/mt.2015.194","article-title":"Development of Novel Adenoviral Vectors to Overcome Challenges Observed With HAdV-5\u2013based Constructs","volume":"24","author":"Papp","year":"2016","journal-title":"Mol. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1002\/elps.201000641","article-title":"Therapeutic plasma proteins\u2014Application of proteomics in process optimization, validation, and analysis of the final product","volume":"32","author":"Kovac","year":"2011","journal-title":"Electrophoresis"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1093\/chromsci\/44.8.479","article-title":"Plasma Protein Fractions in Healthy Blood Donors Quantitated by an Automated Multicapillary Electrophoresis System","volume":"44","author":"Larsson","year":"2006","journal-title":"J. Chromatogr. Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-4939-6737-7_1","article-title":"Antimicrobial Peptides: An Introduction","volume":"Volume 1548","author":"Hansen","year":"2017","journal-title":"Antimicrobial Peptides"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.4049\/jimmunol.176.8.4573","article-title":"Immune Complex-Loaded Dendritic Cells Are Superior to Soluble Immune Complexes as Antitumor Vaccine","volume":"176","author":"Schuurhuis","year":"2006","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1016\/S0022-3476(05)81360-5","article-title":"Cytokines in adenoviral disease in children: Association of interleukin-6, interleukin-8, and tumor necrosis factor alpha levels with clinical outcome","volume":"124","author":"Mistchenko","year":"1994","journal-title":"J. Pediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1111\/j.1651-2227.1992.tb12159.x","article-title":"Participation of immune complexes in adenovirus infection","volume":"81","author":"Mistchenko","year":"1992","journal-title":"Acta Paediatr."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1123","DOI":"10.1126\/science.abb6143","article-title":"Zika virus infection enhances future risk of severe dengue disease","volume":"369","author":"Katzelnick","year":"2020","journal-title":"Science"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.coviro.2020.08.006","article-title":"Protective and enhancing interactions among dengue viruses 1-4 and Zika virus","volume":"43","author":"Katzelnick","year":"2020","journal-title":"Curr. Opin. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Eichholz, K., Bru, T., Tran, T.T.P., Fernandes, P., Welles, H., Mennechet, F.J.D., Manel, N., Alves, P., Perreau, M., and Kremer, E.J. (2016). Immune-Complexed Adenovirus Induce AIM2-Mediated Pyroptosis in Human Dendritic Cells. PLoS Pathog, 12.","DOI":"10.1371\/journal.ppat.1005871"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7058","DOI":"10.4049\/jimmunol.0804269","article-title":"Antiviral Antibodies Target Adenovirus to Phagolysosomes and Amplify the Innate Immune Response","volume":"182","author":"Zaiss","year":"2009","journal-title":"J. Immunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1016\/j.ymthe.2020.01.006","article-title":"Adenovirus-Antibody Complexes Contributed to Lethal Systemic Inflammation in a Gene Therapy Trial","volume":"28","author":"Somanathan","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Tran, T.T.P., Eichholz, K., Amelio, P., Moyer, C., Nemerow, G.R., Perreau, M., Mennechet, F.J.D., and Kremer, E.J. (2018). Humoral immune response to adenovirus induce tolerogenic bystander dendritic cells that promote generation of regulatory T cells. PLoS Pathog, 14.","DOI":"10.1371\/journal.ppat.1007127"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"289","DOI":"10.4161\/cbt.4.3.1499","article-title":"High efficiency transduction of dendritic cells by adenoviral vectors targeted to DC-SIGN","volume":"4","author":"Korokhov","year":"2005","journal-title":"Cancer Biol. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/bs.ai.2015.03.002","article-title":"Cross-Presentation in Mouse and Human Dendritic Cells","volume":"Volume 127","author":"Segura","year":"2015","journal-title":"Advances in Immunology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"19985","DOI":"10.1073\/pnas.1014074107","article-title":"Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21)","volume":"107","author":"Mallery","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1128\/JVI.00050-16","article-title":"Coordinated Neutralization and Immune Activation by the Cytosolic Antibody Receptor TRIM21","volume":"90","author":"Fletcher","year":"2016","journal-title":"J. Virol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"10440","DOI":"10.1073\/pnas.1806314115","article-title":"TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination","volume":"115","author":"Bottermann","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8482","DOI":"10.1128\/JVI.00728-12","article-title":"Regulation of Virus Neutralization and the Persistent Fraction by TRIM21","volume":"86","author":"McEwan","year":"2012","journal-title":"J. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1894","DOI":"10.1016\/S0140-6736(08)61592-5","article-title":"HIV-1 vaccine-induced immunity in the test-of-concept Step Study: A case\u2013cohort analysis","volume":"372","author":"McElrath","year":"2008","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1016\/S0140-6736(08)61591-3","article-title":"Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): A double-blind, randomised, placebo-controlled, test-of-concept trial","volume":"372","author":"Buchbinder","year":"2008","journal-title":"Lancet"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1016\/j.vaccine.2010.12.090","article-title":"Vaccine adjuvants alum and MF59 induce rapid recruitment of neutrophils and monocytes that participate in antigen transport to draining lymph nodes","volume":"29","author":"Calabro","year":"2011","journal-title":"Vaccine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"19940","DOI":"10.1073\/pnas.0907898106","article-title":"Adenovirus vector vaccination induces expansion of memory CD4 T cells with a mucosal homing phenotype that are readily susceptible to HIV-1","volume":"106","author":"Benlahrech","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1016\/j.ymthe.2020.02.010","article-title":"Did Dendritic Cell Activation, Induced by Adenovirus-Antibody Complexes, Play a Role in the Death of Jesse Gelsinger?","volume":"28","author":"Baker","year":"2020","journal-title":"Mol. Ther."},{"key":"ref_39","first-page":"383","article-title":"Monocytes are more susceptible in vitro in rhesus macaques of Chinese origin to recombinant serotype 5 adenovirus with higher preexisting vector specific neutralizing antibody titer","volume":"24","author":"Zhuang","year":"2008","journal-title":"Bing Du Xue Bao"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1038\/ni.1923","article-title":"Complement: A key system for immune surveillance and homeostasis","volume":"11","author":"Ricklin","year":"2010","journal-title":"Nat. Immunol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1016\/S0167-5699(00)01754-0","article-title":"Natural antibodies and complement link innate and acquired immunity","volume":"21","author":"Ochsenbein","year":"2000","journal-title":"Immunol. Today"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1038\/nm1419","article-title":"Generation of C5a in the absence of C3: A new complement activation pathway","volume":"12","author":"Sarma","year":"2006","journal-title":"Nat. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/j.molimm.2004.06.011","article-title":"Complement: A unique innate immune sensor for danger signals","volume":"41","author":"Gasque","year":"2004","journal-title":"Mol. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1146\/annurev.immunol.23.021704.115835","article-title":"Role of C5A in Inflammatory Responses","volume":"23","author":"Guo","year":"2005","journal-title":"Annu. Rev. Immunol."},{"key":"ref_45","first-page":"1794","article-title":"Complement activation by recombinant adenoviruses","volume":"8","author":"Cichon","year":"2001","journal-title":"Gene"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1016\/j.ymthe.2004.08.015","article-title":"Recombinant Adenovirus Vectors Activate the Alternative Complement Pathway, Leading to the Binding of Human Complement Protein C3 Independent of Anti-Ad Antibodies","volume":"10","author":"Jiang","year":"2004","journal-title":"Mol. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1016\/j.chom.2019.02.016","article-title":"Complement C4 Prevents Viral Infection through Capsid Inactivation","volume":"25","author":"Bottermann","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1038\/sj.mt.6300289","article-title":"Interactions Between Human Plasma Components and A Xenogenic Adenovirus Vector: Reduced Immunogenicity During Gene Transfer","volume":"15","author":"Perreau","year":"2007","journal-title":"Mol. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1111\/imr.12473","article-title":"Old dogs-new tricks: Immunoregulatory properties of C3 and C5 cleavage fragments","volume":"274","author":"Verschoor","year":"2016","journal-title":"Immunol. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2321","DOI":"10.4049\/jimmunol.162.4.2321","article-title":"In vitro and in vivo dependency of chemokine generation on C5a and TNF-alpha","volume":"162","author":"Czermak","year":"1999","journal-title":"J. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/0167-5699(91)90009-I","article-title":"The role of complement in inflammation and phagocytosis","volume":"12","author":"Frank","year":"1991","journal-title":"Immunol. Today"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"14622","DOI":"10.1128\/JVI.79.23.14622-14631.2005","article-title":"Neutrophils Interact with Adenovirus Vectors via Fc Receptors and Complement Receptor 1","volume":"79","author":"Cotter","year":"2005","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3306","DOI":"10.4049\/jimmunol.170.6.3306","article-title":"IL-4 Down-Regulates Anaphylatoxin Receptors in Monocytes and Dendritic Cells and Impairs Anaphylatoxin-Induced Migration In Vivo","volume":"170","author":"Soruri","year":"2003","journal-title":"J. Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.imbio.2011.07.016","article-title":"The new face of anaphylatoxins in immune regulation","volume":"217","author":"Zhou","year":"2012","journal-title":"Immunobiology"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"3473","DOI":"10.1182\/blood-2013-05-502229","article-title":"C3a modulates IL-1\u03b2 secretion in human monocytes by regulating ATP efflux and subsequent NLRP3 inflammasome activation","volume":"122","author":"Asgari","year":"2013","journal-title":"Blood"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1242\/jcs.179291","article-title":"Complement-mediated \u201cbystander\u201d damage initiates host NLRP3 inflammasome activation","volume":"129","author":"Suresh","year":"2016","journal-title":"J. Cell Sci."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/j.immuni.2005.02.006","article-title":"C5a Negatively Regulates Toll-like Receptor 4-Induced Immune Responses","volume":"22","author":"Hawlisch","year":"2005","journal-title":"Immunity"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1401","DOI":"10.1038\/nm.2862","article-title":"Anti-inflammatory activity of IgG1 mediated by Fc galactosylation and association of Fc\u03b3RIIB and dectin-1","volume":"18","author":"Karsten","year":"2012","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1172\/JCI26582","article-title":"A regulatory role for the C5a anaphylatoxin in type 2 immunity in asthma","volume":"116","author":"Kohl","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1038\/ni.2499","article-title":"Absence of signaling into CD4+ cells via C3aR and C5aR enables autoinductive TGF-\u03b21 signaling and induction of Foxp3+ regulatory T cells","volume":"14","author":"Strainic","year":"2013","journal-title":"Nat. Immunol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1038\/ni.2140","article-title":"A platelet-mediated system for shuttling blood-borne bacteria to CD8\u03b1+ dendritic cells depends on glycoprotein GPIb and complement C3","volume":"12","author":"Verschoor","year":"2011","journal-title":"Nat. Immunol."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Seiradake, E., Henaff, D., Wodrich, H., Billet, O., Perreau, M., Hippert, C., Mennechet, F., Schoehn, G., Lortat-Jacob, H., and Dreja, H. (2009). The Cell Adhesion Molecule \u201cCAR\u201d and Sialic Acid on Human Erythrocytes Influence Adenovirus In Vivo Biodistribution. PLoS Pathog, 5.","DOI":"10.1371\/journal.ppat.1000277"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1152\/nips.01425.2002","article-title":"Immune Adherence Revisited: Novel Players in an Old Game","volume":"18","author":"Hess","year":"2003","journal-title":"Physiology"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3889","DOI":"10.4049\/jimmunol.141.11.3889","article-title":"Direct evidence for the clustered nature of complement receptors type 1 on the erythrocyte membrane","volume":"141","author":"Paccaud","year":"1988","journal-title":"J. Immunol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/j.bcp.2008.09.017","article-title":"Sepsis, apoptosis and complement","volume":"76","author":"Ward","year":"2008","journal-title":"Biochem. Pharm."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.clim.2009.12.004","article-title":"Antimicrobial peptides: General overview and clinical implications in human health and disease","volume":"135","year":"2010","journal-title":"Clin. Immunol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.it.2008.12.003","article-title":"AMPed up immunity: How antimicrobial peptides have multiple roles in immune defense","volume":"30","author":"Lai","year":"2009","journal-title":"Trends Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"464","DOI":"10.1016\/j.tibtech.2011.05.001","article-title":"The expanding scope of antimicrobial peptide structures and their modes of action","volume":"29","author":"Nguyen","year":"2011","journal-title":"Trends Biotechnol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.drudis.2016.10.017","article-title":"The next generation of antimicrobial peptides (AMPs) as molecular therapeutic tools for the treatment of diseases with social and economic impacts","volume":"22","author":"Cobacho","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1046\/j.1523-1747.2001.01340.x","article-title":"Cutaneous Injury Induces the Release of Cathelicidin Anti-Microbial Peptides Active Against Group A Streptococcus","volume":"117","author":"Dorschner","year":"2001","journal-title":"J. Investig. Dermatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"4132","DOI":"10.1016\/j.jmb.2018.08.011","article-title":"Revised Crystal Structure of Human Adenovirus Reveals the Limits on Protein IX Quasi-Equivalence and on Analyzing Large Macromolecular Complexes","volume":"430","author":"Venkataraman","year":"2018","journal-title":"J. Mol. Biol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.coviro.2011.12.008","article-title":"Structure of human adenovirus","volume":"2","author":"Nemerow","year":"2012","journal-title":"Curr. Opin. Virol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1126\/science.1187292","article-title":"Crystal Structure of Human Adenovirus at 3.5 A Resolution","volume":"329","author":"Reddy","year":"2010","journal-title":"Science"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1182\/blood-2009-03-208835","article-title":"Identification of coagulation factor (F)X binding sites on the adenovirus serotype 5 hexon: Effect of mutagenesis on FX interactions and gene transfer","volume":"114","author":"Alba","year":"2009","journal-title":"Blood"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e00542-20","DOI":"10.1128\/JVI.00542-20","article-title":"Lactoferrin-Hexon Interactions Mediate CAR-Independent Adenovirus Infection of Human Respiratory Cells","volume":"94","author":"Persson","year":"2020","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1189\/jlb.0708412","article-title":"Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91","volume":"86","author":"Presicce","year":"2009","journal-title":"J. Leukoc. Biol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2017","DOI":"10.1172\/JCI114394","article-title":"Monocyte-chemotactic activity of defensins from human neutrophils","volume":"84","author":"Territo","year":"1989","journal-title":"J. Clin. Investig."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2935","DOI":"10.1074\/jbc.271.6.2935","article-title":"Identification of Defensin-1, Defensin-2, and CAP37\/Azurocidin as T-cell Chemoattractant Proteins Released from Interleukin-8-stimulated Neutrophils","volume":"271","author":"Chertov","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1189\/jlb.68.1.9","article-title":"Human neutrophil defensins selectively chemoattract naive T and immature dendritic cells","volume":"68","author":"Yang","year":"2000","journal-title":"J. Leukoc. Biol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1126\/science.286.5439.525","article-title":"\u03b2-Defensins: Linking Innate and Adaptive Immunity Through Dendritic and T Cell CCR6","volume":"286","author":"Yang","year":"1999","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1093\/intimm\/14.4.421","article-title":"Epithelial cell-derived human \u03b2-defensin-2 acts as a chemotaxin for mast cells through a pertussis toxin-sensitive and phospholipase C-dependent pathway","volume":"14","author":"Niyonsaba","year":"2002","journal-title":"Int. Immunol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1819","DOI":"10.1096\/fj.00-0865fje","article-title":"Human \u03b2-defensin 4: A novel inducible peptide with a specific salt-sensitive spectrum of antimicrobial activity","volume":"15","author":"Krause","year":"2001","journal-title":"FASEB J."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"18631","DOI":"10.1073\/pnas.0702130104","article-title":"Human -defensin-3 activates professional antigen-presenting cells via Toll-like receptors 1 and 2","volume":"104","author":"Funderburg","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1096\/fj.07-098038","article-title":"Lactoferrin, a major defense protein of innate immunity, is a novel maturation factor for human dendritic cells","volume":"22","author":"Spadaro","year":"2016","journal-title":"FASEB J."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"6868","DOI":"10.4049\/jimmunol.180.10.6868","article-title":"Lactoferrin Acts as an Alarmin to Promote the Recruitment and Activation of APCs and Antigen-Specific Immune Responses","volume":"180","author":"Yang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1099\/vir.0.008342-0","article-title":"Adenovirus serotype 5 infects human dendritic cells via a coxsackievirus-adenovirus receptor-independent receptor pathway mediated by lactoferrin and DC-SIGN","volume":"90","author":"Adams","year":"2009","journal-title":"J. Gen. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1096\/fj.13-229591","article-title":"Recombinant human lactoferrin induces human and mouse dendritic cell maturation via Toll-like receptors 2 and 4","volume":"28","author":"Spadaro","year":"2014","journal-title":"FASEB J."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"5012","DOI":"10.4049\/jimmunol.1102777","article-title":"The Human Lactoferrin-Derived Peptide hLF1-11 Exerts Immunomodulatory Effects by Specific Inhibition of Myeloperoxidase Activity","volume":"188","author":"Hensbergen","year":"2012","journal-title":"J. Immunol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1084\/jem.192.7.1069","article-title":"Ll-37, the Neutrophil Granule\u2013And Epithelial Cell\u2013Derived Cathelicidin, Utilizes Formyl Peptide Receptor\u2013Like 1 (Fprl1) as a Receptor to Chemoattract Human Peripheral Blood Neutrophils, Monocytes, and T Cells","volume":"192","author":"Yang","year":"2000","journal-title":"J. Exp. Med."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.bbapap.2016.02.013","article-title":"The cationic peptide LL-37 binds Mac-1 (CD11b\/CD18) with a low dissociation rate and promotes phagocytosis","volume":"1864","author":"Zhang","year":"2016","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1729","DOI":"10.1093\/intimm\/dxl107","article-title":"The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands","volume":"18","author":"Kandler","year":"2006","journal-title":"Int. Immunol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.4049\/jimmunol.0902305","article-title":"LL-37 promotes rapid sensing of CpG oligodeoxynucleotides by B lymphocytes and plasmacytoid dendritic cells","volume":"184","author":"Hurtado","year":"2010","journal-title":"J. Immunol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1182\/blood-2012-01-401364","article-title":"Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37","volume":"120","author":"Chamilos","year":"2012","journal-title":"Blood"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1146","DOI":"10.4049\/jimmunol.172.2.1146","article-title":"The cationic antimicrobial peptide LL-37 modulates dendritic cell differentiation and dendritic cell-induced T cell polarization","volume":"172","author":"Davidson","year":"2004","journal-title":"J. Immunol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.chom.2007.12.001","article-title":"Mechanism of adenovirus neutralization by Human alpha-defensins","volume":"3","author":"Smith","year":"2008","journal-title":"Cell Host Microbe"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Flatt, J.W., Kim, R., Smith, J.G., Nemerow, G.R., and Stewart, P.L. (2013). An intrinsically disordered region of the adenovirus capsid is implicated in neutralization by human alpha defensin 5. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0061571"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"4041","DOI":"10.1128\/JVI.02471-09","article-title":"Direct evidence from single-cell analysis that human \u03b1-defensins block adenovirus uncoating to neutralize infection","volume":"84","author":"Nguyen","year":"2010","journal-title":"J. Virol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Smith, J.G., Silvestry, M., Lindert, S., Lu, W., Nemerow, G.R., and Stewart, P.L. (2010). Insight into the mechanisms of adenovirus capsid disassembly from studies of defensin neutralization. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000959"},{"key":"ref_99","first-page":"519","article-title":"Inhibition of adenovirus infection by the bronchoalveolar lavage supernatant in vitro","volume":"8","author":"Skrygan","year":"2003","journal-title":"Eur. J. Med. Res."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Tartaglia, L.J., Badamchi-Zadeh, A., Abbink, P., Blass, E., Aid, M., Gebre, M.S., Li, Z., Pastores, K.C., Trott, S., and Gupte, S. (2019). Alpha-defensin 5 differentially modulates adenovirus vaccine vectors from different serotypes in vivo. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1008180"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2018\/1038593","article-title":"Human Neutrophil Defensin-1, -3, and -4 Are Elevated in Nasal Aspirates from Children with Naturally Occurring Adenovirus Infection","volume":"2018","author":"Priyadharshini","year":"2018","journal-title":"Can. Respir. J."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e02030-16","DOI":"10.1128\/JVI.02030-16","article-title":"Studies on the Interaction of Tumor-Derived HD5 Alpha Defensins with Adenoviruses and Implications for Oncolytic Adenovirus Therapy","volume":"91","author":"Vragniau","year":"2017","journal-title":"J. Virol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1128\/JVI.01995-06","article-title":"Adenoviruses use lactoferrin as a bridge for CAR-independent binding to and infection of epithelial cells","volume":"81","author":"Johansson","year":"2007","journal-title":"J. Virol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/bs.ircmb.2015.10.006","article-title":"Membrane Dynamics and Signaling of the Coxsackievirus and Adenovirus Receptor","volume":"Volume 322","author":"Loustalot","year":"2016","journal-title":"International Review of Cell and Molecular Biology"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"442","DOI":"10.1016\/j.tips.2012.04.005","article-title":"Adenovirus receptors: Implications for targeting of viral vectors","volume":"33","author":"Arnberg","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1754","DOI":"10.1099\/vir.0.030965-0","article-title":"CD209\/DC-SIGN mediates efficient infection of monocyte-derived dendritic cells by clinical adenovirus 2C isolates in the presence of bovine lactoferrin","volume":"92","author":"Mikeler","year":"2011","journal-title":"J. Gen. Virol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"199","DOI":"10.3341\/kjo.2013.27.3.199","article-title":"Anti-adenoviral effects of human cationic antimicrobial protein-18\/LL-37, an antimicrobial peptide, by quantitative polymerase chain reaction","volume":"27","author":"Uchio","year":"2013","journal-title":"Korean J. Ophthalmol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1080\/02713680590934111","article-title":"Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity","volume":"30","author":"Gordon","year":"2005","journal-title":"Curr. Eye Res."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"515","DOI":"10.4103\/0019-5049.144643","article-title":"Overview of the coagulation system","volume":"58","author":"Palta","year":"2014","journal-title":"Indian J. Anaesth."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1073\/pnas.0711757105","article-title":"Adenovirus serotype 5 hexon is critical for virus infection of hepatocytes in vivo","volume":"105","author":"Kalyuzhniy","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2008.01.016","article-title":"Adenovirus Serotype 5 Hexon Mediates Liver Gene Transfer","volume":"132","author":"Waddington","year":"2008","journal-title":"Cell"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2554","DOI":"10.1182\/blood-2006-04-008532","article-title":"Multiple vitamin K-dependent coagulation zymogens promote adenovirus-mediated gene delivery to hepatocytes","volume":"108","author":"Parker","year":"2006","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1795","DOI":"10.1517\/17425247.2014.938637","article-title":"The importance of coagulation factors binding to adenovirus: Historical perspectives and implications for gene delivery","volume":"11","author":"Denby","year":"2014","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"3449","DOI":"10.1002\/1873-3468.13649","article-title":"Interaction of adenovirus with antibodies, complement, and coagulation factors","volume":"593","author":"Allen","year":"2019","journal-title":"FEBS Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"3816","DOI":"10.1128\/JVI.02562-08","article-title":"Coagulation Factors IX and X Enhance Binding and Infection of Adenovirus Types 5 and 31 in Human Epithelial Cells","volume":"83","author":"Jonsson","year":"2009","journal-title":"J. Virol."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2884","DOI":"10.1128\/JVI.03576-14","article-title":"Human Coagulation Factor X-Adenovirus Type 5 Complexes Poorly Stimulate an Innate Immune Response in Human Mononuclear Phagocytes","volume":"89","author":"Eichholz","year":"2015","journal-title":"J. Virol."},{"key":"ref_117","first-page":"109","article-title":"Coagulation factor X mediates adenovirus type 5 liver gene transfer in non-human primates (Microcebus murinus)","volume":"19","author":"Alba","year":"2012","journal-title":"Gene"},{"key":"ref_118","first-page":"1112","article-title":"Murine dendritic cells infected with adenovirus vectors show signs of activation","volume":"7","author":"Hirschowitz","year":"2000","journal-title":"Gene"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1126\/science.1226625","article-title":"Coagulation Factor X Activates Innate Immunity to Human Species C Adenovirus","volume":"338","author":"Doronin","year":"2012","journal-title":"Science"},{"key":"ref_120","doi-asserted-by":"crossref","unstructured":"Gounder, A.P., Myers, N.D., Treuting, P.M., Bromme, B.A., Wilson, S.S., Wiens, M.E., Lu, W., Ouellette, A.J., Spindler, K.R., and Parks, W.C. (2016). Defensins Potentiate a Neutralizing Antibody Response to Enteric Viral Infection. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005474"},{"key":"ref_121","first-page":"263","article-title":"Modulation of classical C3 convertase of complement by tear lactoferrin","volume":"47","author":"Kijlstra","year":"1982","journal-title":"Immunology"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1182\/blood.V92.10.3898","article-title":"Inhibition of Activation of the Classical Pathway of Complement by Human Neutrophil Defensins","volume":"92","author":"Hiemstra","year":"1998","journal-title":"Blood"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nm.3107","article-title":"Coagulation factor X shields adenovirus type 5 from attack by natural antibodies and complement","volume":"19","author":"Xu","year":"2013","journal-title":"Nat. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1016\/j.jconrel.2016.06.022","article-title":"Substitution of blood coagulation factor X-binding to Ad5 by position-specific PEGylation: Preventing vector clearance and preserving infectivity","volume":"235","author":"Krutzke","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1080\/17425247.2019.1617269","article-title":"Achieving systemic delivery of oncolytic viruses","volume":"16","author":"Hill","year":"2019","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1089\/hum.2017.139","article-title":"Capsid Engineering of Adenovirus Vectors: Overcoming Early Vector\u2013Host Interactions for Therapy","volume":"28","author":"Hagedorn","year":"2017","journal-title":"Hum. Gene Ther."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1517\/17425247.2016.1158707","article-title":"Redirecting adenovirus tropism by genetic, chemical, and mechanical modification of the adenovirus surface for cancer gene therapy","volume":"13","author":"Yoon","year":"2016","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1007\/s00441-009-0887-6","article-title":"Proteinases involved in matrix turnover during cartilage and bone breakdown","volume":"339","author":"Cawston","year":"2010","journal-title":"Cell Tissue Res."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1038\/cgt.2011.76","article-title":"Macrophage metalloelastase (MME) as adjuvant for intra-tumoral injection of oncolytic adenovirus and its influence on metastases development","volume":"19","author":"Bauer","year":"2012","journal-title":"Cancer Gene Ther."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/12\/1351\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:37:29Z","timestamp":1760179049000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/12\/12\/1351"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,26]]},"references-count":129,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["v12121351"],"URL":"https:\/\/doi.org\/10.3390\/v12121351","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,26]]}}}