Contacts with environmental biodiversity affect human health: links revealed during the initial waves of the COVID-19 pandemic.

The gradual decrease in the prevalence of serious infectious diseases over the last century has been followed by increase in so called "modern" diseases, including allergies, chronic inflammatory conditions, psychiatric, and metabolic disorders. Between 2019 and 2022, public awareness of the threat of infectious diseases in humans was renewed by the global pandemic of a new type of a coronavirus, the SARS-COV-2. This public interest opened improved possibilities to test hypotheses on the factors associated with inter-individual variation in susceptibility to infectious and "modern" diseases. Based on the Hygiene hypothesis and Biodiversity hypothesis, we predicted that contacts with natural environment and wildlife in childhood and/or in adulthood can improve general health and decrease the risks of severe COVID-19 progression or prevalence of the "modern" diseases, namely the allergies. Here we report the results of an online, self-evaluating questionnaire survey conducted in the Czech Republic, where we contrasted selected health issues, and linked them to the living environment, including the level of contacts with biodiversity. In a sample of 1188 respondents, we revealed a significant association of time spent in nature or contacts with biodiversity with physical and mental health, or incidence of allergies. This is unlike the COVID-19 progression, which was related to age, physical health, smoking, allergies, and interaction of age with smoking, but not to contacts with the natural environmental diversity. Our findings regarding to physical and mental health and allergies are in agreement with the Biodiversity hypothesis of allergy and, linking human and environmental health, they urge for One Health approach application.

Dynamic Evolution of Avian RNA Virus Sensors: Repeated Loss of RIG-I and RIPLET.

Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) are key RNA virus sensors belonging to the RIG-I-like receptor (RLR) family. The activation of the RLR inflammasome leads to the establishment of antiviral state, mainly through interferon-mediated signaling. The evolutionary dynamics of RLRs has been studied mainly in mammals, where rare cases of RLR gene losses were described. By in silico screening of avian genomes, we previously described two independent disruptions of MDA5 in two bird orders. Here, we extend this analysis to approximately 150 avian genomes and report 16 independent evolutionary events of RIG-I inactivation. Interestingly, in almost all cases, these inactivations are coupled with genetic disruptions of RIPLET/RNF135, an ubiquitin ligase RIG-I regulator. Complete absence of any detectable RIG-I sequences is unique to several galliform species, including the domestic chicken (Gallus gallus). We further aimed to determine compensatory evolution of MDA5 in RIG-I-deficient species. While we were unable to show any specific global pattern of adaptive evolution in RIG-I-deficient species, in galliforms, the analyses of positive selection and surface charge distribution support the hypothesis of some compensatory evolution in MDA5 after RIG-I loss. This work highlights the dynamic nature of evolution in bird RNA virus sensors.

Repeated MDA5 Gene Loss in Birds: An Evolutionary Perspective.

Two key cytosolic receptors belonging to the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family sense the viral RNA-derived danger signals: RIG-I and melanoma differentiation-associated protein 5 (MDA5). Their activation establishes an antiviral state by downstream signaling that ultimately activates interferon-stimulated genes (ISGs). While in rare cases RIG-I gene loss has been detected in mammalian and avian species, most notably in the chicken, MDA5 pseudogenization has only been detected once in mammals. We have screened over a hundred publicly available avian genome sequences and describe an independent disruption of MDA5 in two unrelated avian lineages, the storks (Ciconiiformes) and the rallids (Gruiformes). The results of our RELAX analysis confirmed the absence of negative selection in the MDA5 pseudogene. In contrast to our prediction, we have shown, using multiple dN/dS-based approaches, that the MDA5 loss does not appear to have resulted in any compensatory evolution in the RIG-I gene, which may partially share its ligand-binding specificity. Together, our results indicate that the MDA5 pseudogenization may have important functional effects on immune responsiveness in these two avian clades.

Comparative analysis of the chicken IFITM locus by targeted genome sequencing reveals evolution of the locus and positive selection in IFITM1 and IFITM3.

BACKGROUND: The interferon-induced transmembrane (IFITM) protein family comprises a class of restriction factors widely characterised in humans for their potent antiviral activity. Their biological activity is well documented in several animal species, but their genetic variation and biological mechanism is less well understood, particularly in avian species. RESULTS: Here we report the complete sequence of the domestic chicken Gallus gallus IFITM locus from a wide variety of chicken breeds to examine the detailed pattern of genetic variation of the locus on chromosome 5, including the flanking genes ATHL1 and B4GALNT4. We have generated chIFITM sequences from commercial breeds (supermarket-derived chicken breasts), indigenous chickens from Nigeria (Nsukka) and Ethiopia, European breeds and inbred chicken lines from the Pirbright Institute, totalling of 206 chickens. Through mapping of genetic variants to the latest chIFITM consensus sequence our data reveal that the chIFITM locus does not show structural variation in the locus across the populations analysed, despite spanning diverse breeds from different geographic locations. However, single nucleotide variants (SNVs) in functionally important regions of the proteins within certain groups of chickens were detected, in particular the European breeds and indigenous birds from Ethiopia and Nigeria. In addition, we also found that two out of four SNVs located in the chIFITM1 (Ser36 and Arg77) and chIFITM3 (Val103) proteins were simultaneously under positive selection. CONCLUSIONS: Together these data suggest that IFITM genetic variation may contribute to the capacities of different chicken populations to resist virus infection.