TY - JOUR T1 - A Framework to Connect Viral Quasispecies, Microbiome, and Host TT - Viral Quasispecies, Mikrobiyom ve Konak Arasında Bağlantı Kurmak İçin Bir Çerçeve AU - Nehri, Leman Nur AU - Koçoğlu, Seher Elif PY - 2024 DA - September Y2 - 2024 DO - 10.58854/jicm.1465143 JF - Journal of Immunology and Clinical Microbiology JO - J Immunol Clin Microbiol PB - Erkan YULA WT - DergiPark SN - 2528-9470 SP - 73 EP - 88 VL - 9 IS - 3 LA - en AB - Aim: The aim of this study is to investigate the potential interactions between SARS-CoV-2 Spike protein variants and the host microbiota. While the Spike protein is known for its role in mediating viral entry into host cells, its impact on the host’s microbial communities remains unclear. Given the microbiota’s critical role in modulating immune responses and maintaining host homeostasis, understanding these interactions could provide new insights into disease progression and immune evasion mechanisms associated with COVID-19. By leveraging parameters extracted from the current literature and analyzing publicly available datasets, we seek to elucidate how these interactions might influence the severity of COVID-19 and the pathogenesis of emerging viral variants. This research may also highlight potential therapeutic targets for mitigating the effects of SARS-CoV-2 and its evolving forms.Methods: This study investigates the interaction between Spike protein variants of SARS-CoV-2 and the host microbiota. To this end, the associations between various SARS-CoV-2 variants and different host factors derived from urban ecosystems have been statistically analyzed. Specifically, the influence of these host factors, which are linked to distinct microbiota compositions, on the interaction with Spike protein variants has been evaluated. A Bayesian Network approach has been employed for this analysis to model the complex relationships and dependencies among the host factors and microbiota compositions.Results: This study investigates the interaction between Spike protein variants of SARS-CoV-2 and host factors. Hypothesis 1 (H1) posits that specific combinations of various host factors can explain the infectivity of SARS-CoV-2. The analyses reveal that 20 SARS-CoV-2 variants and mutants are significantly affected by various parameters (Table 2), indicating that H1 cannot be rejected. Additionally, it is suggested that the connections mentioned in H1 indicate the presence of a carrier within the host, potentially the microbiome. Hypothesis 2 (H2) proposes that the microbiota serves as the primary carrier of host factors, influencing the selection of specific SARS-CoV-2 mutants. To test this hypothesis, a Bayesian Network was constructed (Figure 3), which identified the probabilistic relationships between potential microbiota compositions and Spike variants.Conclusion: As a result, it is suggested that different Spike protein variants may be present in hosts with varying microbial compositions. Additionally, the microbiota could serve as a carrier that influences the selection of viral mutants in hosts within the population, potentially impacted by external factors such as environmental conditions and human interactions. KW - COVID-19 KW - microbiome KW - Spike protein KW - viral variant KW - host factors N2 - Amaç: Bu çalışmanın amacı, SARS-CoV-2 Spike proteini varyantları ile konak mikrobiotası arasındaki olası etkileşimleri araştırmaktır. Spike proteininin virüsün konak hücrelere girişini sağlamadaki rolü iyi bilinmesine rağmen, bu proteinin konak mikrobiyal topluluklar üzerindeki etkisi belirsizliğini korumaktadır. Mikrobiotanın bağışıklık yanıtlarını düzenlemede ve konak homeostazını sağlamadaki kritik rolü göz önüne alındığında, bu etkileşimlerin incelenmesi, COVID-19’un hastalık ilerleyişi ve bağışıklık kaçışı mekanizmaları hakkında yeni bilgiler sağlayabilir. Literatürdeki mevcut parametreler ve halka açık veri setleri kullanılarak bu etkileşimlerin COVID-19’un şiddeti ve ortaya çıkan virüs varyantlarının patogenezi üzerindeki etkileri araştırılmıştır. Bu araştırma aynı zamanda SARS-CoV-2 ve gelişen varyantlarının etkilerini hafifletmek için potansiyel terapötik hedef olarak mikrobiyotayı ortaya koymayı hedefler.Yöntem: Bu çalışmada, SARS-CoV-2’nin Spike protein varyantları ile konak mikrobiota arasındaki etkileşim incelenmiştir. Bu amaçla, çeşitli SARS-CoV-2 varyantlarının kentsel ekosistemlerden elde edilen farklı konak faktörleriyle ilişkileri istatistiksel olarak analiz edilmiştir. Özellikle, bu konak faktörlerinin, farklı mikrobiota kompozisyonları ile olan etkileşimleri değerlendirilmiştir. Analiz için, konak faktörleri ile mikrobiota kompozisyonları arasındaki karmaşık ilişkileri ve bağımlılıkları modellemek amacıyla Bayesian Ağı yaklaşımı kullanılmıştır.Bulgular: Bu çalışmada, SARS-CoV-2’nin Spike protein varyantları ile konak faktörleri arasındaki etkileşim incelenmiştir. Hipotez 1 (H1), çeşitli konak faktörlerinin belirli kombinasyonlarının SARS-CoV-2’nin enfektifliğini açıklayabileceğini öne sürmüştür. Analizler, 20 SARS-CoV-2 varyantı ve mutantının çeşitli parametrelerden önemli ölçüde etkilendiğini göstermiştir (Tablo 2). Bu sonuç, H1’in reddedilemeyeceğini ortaya koymaktadır. Ek olarak, H1’de belirtilen bağlantıların, konak içinde bir taşıyıcı olduğuna ve bunun mikrobiom olabileceğine işaret ettiği düşünülmektedir. Hipotez 2 (H2) ise, mikrobiotanın konak faktörlerini taşıyarak belirli SARS-CoV-2 mutantlarının seçimini etkileyen ana yapı olduğunu önermektedir. Bu hipotezi test etmek amacıyla oluşturulan Bayesian Ağı (Şekil 3) ile olası mikrobiota kompozisyonlarının Spike varyantları ile olasılıksal ilişkisi tespit edilmiştir. Sonuç: Sonuç olarak, farklı Spike protein varyantlarının farklı mikrobiyal kompozisyonlara sahip konaklarda bulunabileceği önerilmektedir. Ayrıca, mikrobiota, konaklardaki viral mutantların seçimini etkileyebilecek bir taşıyıcı rolü üstlenebilir; bu etki, çevresel koşullar ve insan etkileşimleri gibi dış faktörlerden etkilenebilir. CR - Avanzato, V. A., Matson, M. J., Seifert, S. N., Pryce, R., Williamson, B. N., Anzick, S. L., Barbian, K., Patel, A., Judson, S. D., Bowman, K., Martens, C., Li, D., Fischer, R. J., Munster, V. J., & Kuhn, J. H. (2020). Case study: Prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer. Cell, 183(7), 1901-1912.e9. https://doi.org/10.1016/j.cell.2020.10.049 CR - Bal, A., Destras, G., Gaymard, A., Stefic, K., Marlet, J., Eymieux, S., Billaud, G., Laurent, F., Gonzalez, C., Valette, M., & Li-na, B. (2021). Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69–V70, France, August to December 2020. Eurosurveillance, 26(3), 2100008. https://doi.org/10.2807/1560-7917.ES.2021.26.3.2100008 CR - Banerjee, S., Schlaeppi, K., & van der Heijden, M. G. A. (2018). Keystone taxa as drivers of microbiome structure and functioning. Nature Reviews Microbiology, 16(9), 567–576. https://doi.org/10.1038/s41579-018-0024-1 CR - Boni, M. F., Lemey, P., Jiang, X., Lam, T. T.-Y., Perry, B. W., Castoe, T. A., Rambaut, A., & Robertson, D. L. (2020). Evolutio-nary origins of the SARS-CoV-2 sarbecovirus lineage responsible for the COVID-19 pandemic. Nature Microbiology, 5(11), 1408–1417. https://doi.org/10.1038/s41564-020-0771-4 CR - Bradley, P. H., & Pollard, K. S. (2017). Proteobacteria explain significant functional variability in the human gut microbio-me. Microbiome, 5(1), 36. https://doi.org/10.1186/s40168-017-0244-z CR - Bresalier, R. S., & Chapkin, R. S. (2020). Human microbiome in health and disease: The good, the bad, and the bugly. Di-gestive Diseases and Sciences, 65(3), 671–673. https://doi.org/10.1007/s10620-020-06059-y CR - Bruijning, M., Henry, L. P., Forsberg, S. K. G., Metcalf, J. E., & Ayroles, J. F. (2020). When the microbiome defines the host phenotype: Selection on vertical transmission in varying environments. bioRxiv. https://doi.org/10.1101/2020.04.28.066134 CR - Bui, N.-N., Lin, Y.-T., Huang, S.-H., & Lin, C.-W. (2022). Haplotype distribution of SARS-CoV-2 variants in low and high vac-cination rate countries during ongoing global COVID-19 pandemic in early 2021. Infection, Genetics and Evolution, 97, 105164. https://doi.org/10.1016/j.meegid.2021.105164 CR - Corman, V. M., Muth, D., Niemeyer, D., & Drosten, C. (2018). Hosts and sources of endemic human coronaviruses. Advan-ces in Virus Research, 100, 163–188. https://doi.org/10.1016/bs.aivir.2018.01.001 CR - Corman, V. M., Muth, D., Niemeyer, D., & Drosten, C. (2019). Hosts and sources of endemic human coronaviruses. Advan-ces in Virus Research, 100, 163–188. https://doi.org/10.1016/bs.aivir.2018.01.001 CR - Das, B., Nair, G. B., Pal, A., Ramamurthy, T., Ganguly, S., Majumder, K. K., & Sarkar, B. L. (2018). Gut microbiota of healthy and malnourished children in India. Scientific Reports, 8(1), 3215. https://doi.org/10.1038/s41598-018-21594-4 CR - Dhar, D., & Mohanty, A. (2020). Gut microbiota and COVID-19—Possible link and implications. Virus Research, 285, 198018. https://doi.org/10.1016/j.virusres.2020.198018 CR - Donaldson, G. P., Lee, S. M., & Mazmanian, S. K. (2018). Gut microbiota utilize immunoglobulin A for mucosal colonization. Science, 360(6390), 795–800. https://doi.org/10.1126/science.aaq0926 CR - Focosi, D., Maggi, F., Franchini, M., McConnell, S., & Casadevall, A. (2021). Analysis of immune escape variants from anti-body-based therapeutics against COVID-19: A systematic review. International Journal of Molecular Sciences, 23(1), 29. https://doi.org/10.3390/ijms23010029 CR - Gorbalenya, A. E., Baker, S. C., Baric, R. S., de Groot, R. J., Drosten, C., Gulyaeva, A. A., Haagmans, B. L., Lauber, C., Leon-tovich, A. M., Neuman, B. W., Penzar, D., Perlman, S., Poon, L. L. M., Samborskiy, D., Sidorov, I. A., Sola, I., & Ziebuhr, J. (2020). The species severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2. Nature Microbiology, 5(4), 536–544. https://doi.org/10.1038/s41564-020-0695-z CR - Huang, S., Chai, Y., Zhang, L., Wang, X., Wang, H., Zhang, L., Shi, Z., & Fu, J. (2020). Population genetic structure of SARS-CoV-2 spike gene mutations. Genome Biology and Evolution, 12(11), 1988–2001. https://doi.org/10.1093/gbe/evaa240 CR - Kahn, J. S. (2020). Nidovirales. Encyclopedia of Virology, 419–430. https://doi.org/10.1016/B978-0-12-809633-8.21501-X CR - Knezevic, J., Starchl, C., Berisha, A. T., & Amrein, K. (2021). Thyroid-gut-axis: How does the microbiota influence thyroid function? Nutrients, 12(6), 1769. https://doi.org/10.3390/nu12061769 CR - Lazar, V., Ditu, L.-M., & Popescu, G. (2018). Aspects of gut microbiota and immune system interactions in infectious dise-ases, immunopathology, and cancer. Frontiers in Immunology, 9, 1830. https://doi.org/10.3389/fimmu.2018.01830 CR - Leibold, M. A., Holyoak, M., Mouquet, N., Amarasekare, P., Chase, J. M., Hoopes, M. F., Holt, R. D., Shurin, J. B., Law, R., Tilman, D., Loreau, M., & Gonzalez, A. (2004). The metacommunity concept: A framework for multi-scale community eco-logy. Ecology Letters, 7(7), 601–613. https://doi.org/10.1111/j.1461-0248.2004.00608.x CR - Loftus, M., Hassouneh, S. A.-D., & Yooseph, S. (2021). Bacterial associations in the healthy human gut microbiome across populations. Scientific Reports, 11(1), 2828. https://doi.org/10.1038/s41598-021-82449-0 CR - Manor, O., Levy, R., Popejoy, A. B., & McMurry, R. (2020). Health and disease markers correlate with gut microbiome composition across thousands of people. Nature Communications, 11(1), 5206. https://doi.org/10.1038/s41467-020-18871-1 CR - Marchesi, J. R., & Ravel, J. (2015). The vocabulary of microbiome research: A proposal. Microbiome, 3(1), 31. https://doi.org/10.1186/s40168-015-0094-5 CR - Miller, E. T., Svanbäck, R., & Bohannan, B. J. M. (2018). Microbiomes as metacommunities: Understanding host-associated microbes through metacommunity ecology. Trends in Ecology & Evolution, 33(12), 926–935. https://doi.org/10.1016/j.tree.2018.09.002 CR - Mobeen, F., Sharma, V., & Prakash, T. (2018). Enterotype variations of the healthy human gut microbiome in different ge-ographical regions. Bioinformation, 14(9), 560–573. https://doi.org/10.6026/97320630014560 CR - Pérez-Losada, M., Arenas, M., Galán, J. C., Palero, F., & González-Candelas, F. (2015). Recombination in viruses: Mecha-nisms, methods of study, and evolutionary consequences. Infection, Genetics and Evolution, 30, 296–307. https://doi.org/10.1016/j.meegid.2014.12.022 CR - Pickard, J. M., Zeng, M. Y., Caruso, R., & Núñez, G. (2017). Gut microbiota: Role in pathogen colonization, immune respon-ses, and inflammatory disease. Immunological Reviews, 279(1), 70–89. https://doi.org/10.1111/imr.12567 CR - Rinninella, E., Raoul, P., Cintoni, M., Franceschi, F., Miggiano, G. A. D., Gasbarrini, A., & Mele, M. C. (2019). What is the healthy gut microbiota composition? A changing ecosystem across age, environment, diet, and diseases. Microorganisms, 7(1), 14. https://doi.org/10.3390/microorganisms7010014 CR - Scanlan, P. D. (2019). Microbial evolution and ecological opportunity in the gut environment. Proceedings of the Royal Society B: Biological Sciences, 286(1915), 20191964. https://doi.org/10.1098/rspb.2019.1964 CR - Scepanovic, P., Hübenthal, M., Lauc, G., & Kreplin, D. (2019). A comprehensive assessment of demographic, environmen-tal, and host genetic associations with gut microbiome diversity in healthy individuals. Microbiome, 7(1), 130. https://doi.org/10.1186/s40168-019-0747-x CR - Segal, L. N., & Blaser, M. J. (2014). A brave new world: The lung microbiota in an era of change. Annals of the American Thoracic Society, 11(Supplement 1), S21–S27. https://doi.org/10.1513/AnnalsATS.201306-189MG CR - Sencio, V., Machado, M. G., & Trottein, F. (2021). The lung–gut axis during viral respiratory infections: The impact of gut dysbiosis on secondary disease outcomes. Mucosal Immunology, 14(2), 296–304. https://doi.org/10.1038/s41385-020-00361-8 CR - Shreiner, A. B., Kao, J. Y., & Young, V. B. (2015). The gut microbiome in health and in disease. Current Opinion in Gastroen-terology, 31(1), 69–75. https://doi.org/10.1097/MOG.0000000000000139 CR - Simon-Loriere, E., & Holmes, E. C. (2011). Why do RNA viruses recombine? Nature Reviews Microbiology, 9(8), 617–626. https://doi.org/10.1038/nrmicro2614 CR - Singh, B. K., Bardgett, R. D., Smith, P., & Reay, D. S. (2010). Microorganisms and climate change: Terrestrial feedbacks and mitigation options. Nature Reviews Microbiology, 8(11), 779–790. https://doi.org/10.1038/nrmicro2439 CR - Töpfer, A., Zagordi, O., Prabhakaran, S., Roth, V., Halperin, E., & Beerenwinkel, N. (2013). Probabilistic inference of viral quasispecies subject to recombination. Journal of Computational Biology, 20(2), 113–123. https://doi.org/10.1089/cmb.2012.0232 CR - Thursby, E., & Juge, N. (2017). Introduction to the human gut microbiota. Biochemical Journal, 474(11), 1823–1836. https://doi.org/10.1042/BCJ20160510 CR - Trosvik, P., & de Muinck, E. J. (2015). Ecology of bacteria in the human gastrointestinal tract—Identification of keystone and foundation taxa. Microbiome, 3(1), 44. https://doi.org/10.1186/s40168-015-0107-4 CR - Walls, A. C., Park, Y.-J., Tortorici, M. A., Wall, A., McGuire, A. T., & Veesler, D. (2020). Structure, function, and antigenicity of the SARS-CoV-2 spike glycoprotein. Cell, 181(2), 281-292.e6. https://doi.org/10.1016/j.cell.2020.02.058 CR - Yeoh, Y. K., Zuo, T., Lui, G. C.-Y., Zhang, F., Liu, Q., Li, A. Y., Chung, A. C.-K., Cheung, C. P., Tso, E. Y.-K., Fung, K. S. C., & Chan, F. K. L. (2021). Gut microbiota composition reflects disease severity and dysfunctional immune responses in pati-ents with COVID-19. Gut, 70(4), 698–706. https://doi.org/10.1136/gutjnl-2020-323020 CR - Zheng, D., Liwinski, T., & Elinav, E. (2020). Interaction between microbiota and immunity in health and disease. Cell Rese-arch, 30(6), 492–506. https://doi.org/10.1038/s41422-020-0332-7 CR - Zhou, P., Yang, X.-L., Wang, X.-G., Hu, B., Zhang, L., Zhang, W., Si, H.-R., Zhu, Y., Li, B., Huang, C.-L., Chen, H.-D., Chen, J., Luo, Y., Guo, H., Jiang, R.-D., Liu, M.-Q., Chen, Y., Shen, X.-R., Wang, X., ... Shi, Z.-L. (2020). A pneumonia outbreak associ-ated with a new coronavirus of probable bat origin. Nature, 579(7798), 270–273. https://doi.org/10.1038/s41586-020-2012-7 UR - https://doi.org/10.58854/jicm.1465143 L1 - https://dergipark.org.tr/tr/download/article-file/3848183 ER -