Home Medizin Die genetische Ausstattung von Schuppentieren ist mit einer erhöhten Anfälligkeit für Coronaviren verbunden

Die genetische Ausstattung von Schuppentieren ist mit einer erhöhten Anfälligkeit für Coronaviren verbunden

von NFI Redaktion

A study published in the journal Scientific Reports explains that the susceptibility of pangolins to coronavirus infection may be due to their innate gene pseudogenization.


Eine RNA-Seq-Analyse des Coronavirus in der Haut des Schuppentiers










Study: A RNA-Seq analysis of the coronavirus in the pangolin skin. Image credit: Makabas / Shutterstock

Background

Pangolins are 30-100 cm long ant-eating mammals found in Africa and Asia. The populations of all eight pangolin species are declining on these continents. Four pangolin species from Africa are now considered „vulnerable“ or „endangered“; three species from East Asia are „critically endangered“; and one species from India is „endangered“.

The greatest obstacle to pangolin conservation is the high susceptibility and frequent mortality of captive pangolins due to infections. It is believed that the pseudogenization of immune system genes in the pangolin genome is the primary factor for their high infection susceptibility. These pseudogenes include Interferon Epsilon (IFNE), Interferon-Induced with Helicase C-Domain 1, Cyclic GMP-AMP Synthase, Stimulator of Interferon Genes, Toll-Like Receptor 5, and Toll-Like Receptor 11.

The researchers of the current study previously analyzed brain and lung samples of a Malayan pangolin and found a coronavirus infection closely related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the recent coronavirus disease 2019 (COVID-19) pandemic.

In the current study, scientists conducted an RNA-Seq analysis of pangolin skin tissue to understand the transcriptional antiviral response in pangolin skin, particularly in the context of Interferon Epsilon (IFNE) deficiency, a unique immune feature of pangolins.

They compared the expression of differentially expressed genes (DEGs) between coronavirus-infected pangolin skin and healthy pangolin skin. They also compared these DEGs with those found in coronavirus-infected human lungs, as there was no corresponding dataset available for coronavirus-infected human skin. Since humans and pangolins are mammals, the researchers expected certain similarities in immune responses between human lungs and pangolin skin.

Endogenous retrovirus genes are remnants of once infectious exogenous retroviruses that have settled in the genome of humans or other animals. They can modulate the innate immune system and facilitate antiviral immune responses through various mechanisms. In this study, the researchers also examined how endogenous retrovirus gene expression in pangolins responds to a coronavirus infection, specifically in relation to IFNE deficiency.

Key Observations

The scientists identified the RNA of pangolin coronavirus in the skin of the Malayan pangolin. This virus is closely related to another pangolin coronavirus, MP789, isolated from the Guangdong pangolin. Since both pangolins were held at the Guangdong Wildlife Rescue Center, the scientists assume that both coronaviruses originate from the same source.

Comparative analysis of DEGs between pangolin skin and human lungs identified 2,835 pangolin skin-specific DEGs, 1,527 human lung-specific DEGs, and 366 common DEGs. Enriched signaling pathways were identified in pangolin skin-specific DEGs, including malaria and Staphylococcus aureus infection pathways (upregulated) and arachidonic acid metabolism pathways (downregulated). The malaria pathway was also upregulated in human lungs.

Previous studies have shown that malaria pathways are upregulated after SARS-CoV-2 infection and that anti-malaria drugs can suppress SARS-CoV-2 replication. Similarly, arachidonic acid pathways have an inhibitory effect on coronavirus replication. Therefore, the results of the comparative analysis suggest that both the malaria pathway and the arachidonic acid pathway can serve as potential targets for combating coronavirus infection in pangolins.

Further analysis of pathway enrichment revealed that the most highly upregulated pathways in pangolin skin were the COVID-19 pathway, immune and inflammation pathways (except IFN), cell proliferation pathways, and coagulation pathways. These results are consistent with those observed in humans infected with SARS-CoV-2. In contrast, no enrichment of IFN-specific pathways was observed in infected skin. This could be related to a natural IFNE deficiency in pangolins.

High expression levels of many endogenous retrovirus genes were observed in healthy pangolin skin samples. This could be beneficial for pangolins as it strengthens innate immune responses in the absence of IFNE responses. However, a downregulation of these genes was observed in coronavirus-infected skin samples. This suggests that the pangolin coronavirus could suppress endogenous retrovirus gene expression to support virus replication.

Study Significance

The study demonstrates replicating coronavirus in the skin of the Malayan pangolin and provides transcriptomic landscapes of the host’s immune response to a coronavirus infection. The study also concludes that downstream pathways of lost immune system genes in response to infection are not upregulated. This emphasizes that pseudogenization of key immune-related genes significantly modulates pangolins‘ antiviral responses and makes them susceptible to coronavirus infection.

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