Spezifische Infektionen als Auslöser von Krebs und chronischen neuronalen Erkrankungen
Tóm tắt
Manche Viren, Bakterien und parasitäre Infektionen können zu Krebserkrankungen führen. Neben der direkten infektiösen Karzinogenese bei Verbleib von Erregergenen in den Zellen gibt es zumindest zwei Mechanismen der indirekten infektionsbedingten Krebsentstehung: Immunsuppression und chronische Entzündungen mit Radikalbildung und mutagener Aktivität in proliferierenden Zellen. Studien legen nahe, dass bei bestimmten Krebsarten des Menschen nach spezifischen Erregern gesucht werden sollte, die vermutlich nicht als direkte infektiöse Krebserreger eine Rolle spielen, sondern eher über einen indirekten Mechanismus auf Krebsvorläuferzellen und später auch auf Krebszellen einwirken. Die Epidemiologie der betreffenden Krebsarten und chronischen Infektionen legt nahe, dass der Verzehr von Milch- und Fleischprodukten unserer Milchrinder hier eine besondere Rolle spielt und dass wir es mit unerwartet weit verbreiteten Zoonosen des Menschen zu tun haben, deren Identifizierung eine Reihe von Konsequenzen für künftige Präventions- und Therapiemaßnahmen mit sich bringen dürfte. Auch bei der multiplen Sklerose (MS) wird ein ätiologischer Zusammenhang mit Infektionen (vor allem Epstein-Barr-Virus [EBV], seltener humanes Herpesvirus Typ 6) sowie ein Bezug zum Kuhmilch- und Rindfleischkonsum angenommen. In autopsierten MS-Läsionen wurden zirkuläre DNA-Moleküle („multiple sclerosis brain isolate“ 1 und 2 [MSBI‑1 und MSBI-2]) isoliert, die strukturell DNA-Molekülen aus Milch und Rinderblut („bovine meat and milk factors“ [BMMF]) ähneln. Gemäß einem aktuellen ätiologischen Modell ist eine Doppelinfektion spezifischer Hirnzellen durch EBV und BMMF Ausgangspunkt der MS-Entstehung. Zunächst erfolgt eine Reaktivierung von EBV, etwa durch einen Vitamin-D3-Mangel und die resultierende Synthese von „transforming growth factor β“ (TGF-β). Die reaktivierten Herpesviren amplifizieren dann die BMMF-DNA, die schließlich freigesetzt wird und in benachbarte Zellen gelangt. Eine fokale Immunantwort führt zur Zerstörung von BMMF-Protein-produzierenden Zellen und damit zum Erkrankungsbeginn.
Tài liệu tham khảo
Ajdacic-Gross V, Schmid M, Mutsch M et al (2017) The change in the sex ratio in multiple sclerosis is driven by birth cohort effects. Eur J Neurol 24(1):98–104
Andrés-Benito P, Carmona M, Douet JY et al (2021) Differential astrocyte and oligodendrocyte vulnerability in murine Creutzfeldt-Jakob disease. Prion 1:112–120
Archer F, Bachelin C, Andreoletti O et al (2004) Cultured peripheral neuroglial cells are highly permissive to sheep prion infection. J Virol 78(1):482–490
Atmaca MM, Altiokka Uzun G, Shugaiv E et al (2015) Association of demyelinating and inflammatory bowel diseases: a case series and overview of the literature. Noro Psikiyatr Ars 52(3):315–318
Bauer G, Höfler P, zur Hausen H (1982) Epstein-Barr virus induction by a serum factor. I. Induction and cooperation with additional inducers. Virology 121:184–194
Bjornevik K, Cortese M, Healy BC et al (2022) Longitudinal analysis reveals high prevalence of Epstein-Barr virus associated with multiple sclerosis. Science 375:296–301
Borkosky SS, Whitley C, Kopp-Schneider A et al (2012) Epstein-Barr virus stimulates torque teno virus replication: a possible relationship to multiple sclerosis. Plos One 7:e32160
Chen H, Zhang J, Wang T et al (2021) Type 2 diabetes mellitus and Amyotrophic lateral sclerosis: genetic overlap, causality, and mediation. J Clin Endocrinol Metab 106:e4497–e4508
Coghill AE, Engels EA, Schymura MJ et al (2018) Risk of breast, prostate, and colorectal cancer diagnoses among HIV-infected individuals in the United States. J Natl Cancer Inst 110:959–966
Ellermann V, Bang O (1908) Experimentelle Leukämie bei Hühnern. Zentralbl Bakteriol Parasitenkd Infektionskr Hyg 46:595–597
Farvid MS, Sidahmed E, Spence ND et al (2021) Consumption of red meat and processed meat and cancer incidence: a systematic review and meta-analysis of prospective studies. Eur J Epidemiol 36:937–951
Faupel-Badger JM, Arcaro KF, Balkam JJ et al (2013) Postpartum remodeling, lactation, and breast cancer risk: summary of a National Cancer Institute-sponsored workshop. J Natl Cancer Inst 105:166–174
Fawcett DW (1956) Electron microscope observations of intracellular virus-like particles associated with the cells of the Lucké renal adenocarcinoma. J Biophys Biochem Cytol 2:725–741
Follett KJ, Hess TM (2002) Aging, cognitive complexity, and the fundamental attribution error. J Gerontol B Psychol Sci Soc Sci 57(4):P312–P323
Forbes JD, Van Domselaar G, Bernstein CN (2014) The gut microbiota in immune-mediated inflammatory diseases. Front Microbiol 7:1081
Funk M, Gunst K, Lucansky V et al (2014) Isolation of protein-associated circular DNA from healthy cattle serum. Genome Announc 2(4):e846
Georg-Fries B, Biederlack S, Wolf J et al (1984) Analysis of proteins, helper dependence, and seroepidemiology of a new human parvovirus. Virology 134:64–71
González-Jiménez E, García PA, Aguilar MJ et al (2014) Breastfeeding and the prevention of breast cancer: a retrospective review of clinical histories. J Clin Nurs 23:2397–2403
Gunst K, zur Hausen H, de Villiers EM (2014) Isolation of bacterial plasmid-related replication-associated circular DNA from a serum sample of a multiple sclerosis patient. Genome Announc 2(4):e847–14
Haab BB, Klamer Z (2020) Advances in tools to determine the glycan-binding specificities of lectins and antibodies. Mol Cell Proteomics 19:224–232
Heilbronn R, zur Hausen H (1989) A subset of herpes simplex virus replication genes induces DNA amplification within the host cell genome. J Virol 63:3683–3692
Heilbronn R, Albrecht I, Stephan S et al (1993) Human cytomegalovirus induces JC virus DNA replication in human fibroblasts. Proc Natl Acad Sci USA 90:11406–11410
Hou WH, Li CY, Chang HH et al (2017) A population-based cohort study suggests an increased risk of multiple sclerosis incidence in patients with type 2 diabetes mellitus. J Epidemiol 27:235–241
Jelcic I, Hotz-Wagenblatt A, Hunziker A et al (2004) Isolation of multiple TT virus genotypes from spleen biopsy tissue from a Hodgkin’s disease patient: genome reorganization and diversity in the hypervariable region. J Virol 78:7498–7507
Klein G (1972) Herpesviruses and oncogenesis. Proc Natl Acad Sci USA 69:1056–1064
Kosmidou M, Katsanos AH, Katsanos KH et al (2017) Multiple sclerosis and inflammatory bowel diseases: a systematic review and meta-analysis. J Neurol 264:254–259
Kuusisto H, Hyöty H, Kares S et al (2008) Human herpes virus 6 and multiple sclerosis: a Finnish twin study. Mult Scler 14:54–58
Lamberto I, Gunst K, Müller H et al (2014) Mycovirus-like DNA virus sequences from cattle serum and human brain and serum samples from multiple sclerosis patients. Genome Announc 2(4):e848–14
Leppik L, Gunst K, Lehtinen M et al (2007) In vivo and in vitro intragenomic rearrangement of TT viruses. J Virol 81:9346–9356
Manuelidis L (2011) Nuclease resistant circular DNAs copurify with infectivity in scrapie and CJD. J Neurovirol 17:131–145
Martín-Sosa S, Martín MJ, Hueso P (2002) The sialylated fraction of milk oligosaccharides is partially responsible for binding to enterotoxigenic and uropathogenic Escherichia coli human strains. J Nutr 132:3067–3072
McDougall JK, Vause KE, Gallimore PH et al (1974) Cytogenetic studies in permissive and abortive infections by adenovirus type 12. Int J Cancer 14:236–243
Menet A, Speth C, Larcher C et al (1999) Epstein-Barr virus infection of human astrocyte cell lines. J Virol 73:7722–7733
Peyrin-Biroulet L, Oussalah A, Bigard MA (2009) Crohn’s disease: the hot hypothesis. A low vitamin D status has now been linked to several Th1-mediated autoimmune diseases, including multiple sclerosis, type 1 diabetes and rheumatoid arthritis, with the strongest evidence for the vitamin’s protective role in multiple sclerosis. Med Hypotheses 73:94–96
Pike MC, Pearce CL, Wu AH (2004) Prevention of cancers of the breast, endometrium and ovary. Oncogene 23:6379–6391
Pormohammad A, Azimi T, Falah F et al (2018) Relationship of human herpes virus 6 and multiple sclerosis: a systematic review and meta-analysis. J Cell Physiol 233:2850–2862
Ricca C, Aillon A, Viano M et al (2019) Vitamin D inhibits the epithelial-mesenchymal transition by a negative feedback regulation of TGF‑β activity. J Steroid Biochem Mol Biol 187:97–105
Rigoni-Stern D (1842) Fatti statistici relativi alle malatia cancerose. G Serv Prog Pathol Therap 2:507
Schlehofer JR, Gissmann L, Matz B et al (1983a) Herpes simplex virus-induced amplification of SV40 sequences in transformed Chinese hamster embryo cells. Int J Cancer 32:99–103
Schlehofer JR, Heilbronn R, Georg-Fries B et al (1983b) Inhibition of initiator-induced SV40 gene amplification in SV40-transformed Chinese hamster cells by infection with a defective parvovirus. Int J Cancer 32:591–595
Schmitt J, Schlehofer JR, Mergener K et al (1989) Amplification of bovine papillomavirus DNA by N‑methyl-N’-nitro-N-nitrosoguanidine, ultraviolet irradiation, or infection with herpes simplex virus. Virology 172:73–81
Shirvani-Farsani Z, Behmanesh M, Mohammadi SM et al (2015) Naser Moghadasi A Vitamin D levels in multiple sclerosis patients: association with TGF-β2, TGF-βRI, and TGF-βRII expression. Life Sci 134:63–57
Sonnenberg A, Ajdacic-Gross V (2018) Similar birth-cohort patterns in Crohn’s disease and multiple sclerosis. Mult Scler 24:140–149
Sospedra M, Zhao Y, zur Hausen H et al (2005) Recognition of conserved amino acid motifs of common viruses and its role in autoimmunity. PLoS Pathog 1:e41. https://doi.org/10.1371/journal.ppat.00100
Sporn MB (2006) The early history of TGF-beta, and a brief glimpse of its future. Cytokine Growth Factor Rev 17:3–7
Tarlinton RE, Martynova E, Rizvanov AA et al (2020) Role of viruses in the pathogenesis of multiple sclerosis. Viruses 12(6):643. https://doi.org/10.3390/v12060643
Ten Bosch GJA, Bolk J, ’t Hart BA et al (2021) Multiple sclerosis is linked to MAPKERK overactivity in microglia. J Mol Med 99:1033–1042
Thai JD, Gregory KE (2020) Bioactive factors in human breast milk attenuate intestinal inflammation during early life. Nutrients 12:581
Thurl S, Munzert M, Boehm G et al (2017) Systematic review of the concentrations of oligosaccharides in human milk. Nutr Rev 75:920–933
Troisi R, Bjørge T, Gissler M et al (2018) The role of pregnancy, perinatal factors and hormones in maternal cancer risk: a review of the evidence. J Intern Med 283:430–445
Varki A (2010) Colloquium paper: uniquely human evolution of sialic acid genetics and biology. Proc Natl Acad Sci USA 107(Suppl 2):8939–8946
de Villiers EM, zur Hausen H (2009) TT viruses—the still elusive human pathogens. Preface. Curr Top Microbiol Immunol 331:v–vi. PMID: 19230553
de Villiers EM, zur Hausen H (2021) Bovine meat and milk factors (BMMFs): their proposed role in common human cancers and type 2 diabetes mellitus. Cancers 13:5407
de Villiers EM, Gunst K, Chakraborty D et al (2019) A specific class of infectious agents isolated from bovine serum and dairy products and peritumoral colon cancer tissue. Emerg Microbes Infect 8:1205–1218
Walton C, King R, Rechtman L et al (2020) Rising prevalence of multiple sclerosis worldwide: Insights from the Atlas of MS, third edition. Multi Scler 26:1816–1821
Whitley C, Gunst K, Müller H et al (2014) Novel replication-competent circular DNA molecules from healthy cattle serum and milk and multiple sclerosis-affected human brain tissue. Genome Announc 2:e849–14
Willett WC (1997) Nutrition and cancer. Salud Publica Mex 39:298–309
zur Hausen H (1967) Induction of specific chromosomal aberrations by adenovirus type 12 in human embryonic kidney cells. J Virol 1:1174–1185
zur Hausen H (2001a) Oncogenic DNA viruses. Oncogene 20:7820–7823
zur Hausen H (2001b) Proliferation-inducing viruses in non-permissive systems as possible causes of human cancers. Lancet 357:381–384
zur Hausen H (2006) Infections, causing human cancer. Wiley-VCH, Weinheim
zur Hausen H (2012) Red meat consumption and cancer: reasons to suspect involvement of bovine infectious factors in colorectal cancer. Int J Cancer 130:2475–2483
zur Hausen H, de Villiers EM (2015) Dairy cattle serum and milk factors contributing to the risk of colon and breast cancers. Int J Cancer 137:959–967
zur Hausen H, Bund T, de Villiers EM (2017) Infectious agents in bovine red meat and milk and their potential role in cancer and other chronic diseases. Curr Top Microbiol Immunol 407:83–116
zur Hausen H, de Villiers EM (2014) Cancer “causation” by infections—individual contributions and synergistic networks. Semin Oncol 41:860–875
zur Hausen H (2015) Risk factors: what do breast and CRC cancers and MS have in common? Nat Rev Clin Oncol 12:569–570