Viral Quasispecies, Mikrobiyom ve Konak Arasında Bağlantı Kurmak İçin Bir Çerçeve

Öz

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.

Anahtar Kelimeler

• COVID-19
• Mikrobiyom
• Spike Proteini
• Viral Varyant
• Konak Faktörler

A Framework to Connect Viral Quasispecies, Microbiome, and Host

Öz

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.

Anahtar Kelimeler

• COVID-19
• microbiome
• Spike protein
• viral variant
• host factors

Kaynakça

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