Compared with terrestrial mammals, bats have a longer lifespan and greater capacity to co-exist with a variety of viruses. In addition to cytosolic DNA generated by these viral infections, the metabolic demands of flight cause DNA damage and the release of self-DNA into the cytoplasm. However, whether bats have an altered DNA sensing/defense system to balance high cytosolic DNA levels remains an open question. We demonstrate that bats have a dampened interferon response due to the replacement of the highly conserved serine residue (S358) in STING, an essential adaptor protein in multiple DNA sensing pathways. Reversing this mutation by introducing S358 restored STING functionality, resulting in interferon activation and virus inhibition. Combined with previous reports on bat-specific changes of other DNA sensors such as TLR9, IFI16, and AIM2, our findings shed light on bat adaptation to flight, their long lifespan, and their unique capacity to serve as a virus reservoir.
Bats have received increasing attention because of some unique biological features they possess. TRIM is a large family of proteins that participate in diverse cellular functions, such as antiviral immunity, DNA damage repair, tumor suppression, and aging. These functional areas appear to be highly consistent with the special characteristics of bats, such as tolerance to viruses and DNA damage generated in flight, low cancer incidence, and longevity. However, there is still a lack of systematic study of the TRIM family in bats. Here, we explored the TRIM family of bats using the genomes of 16 representative species. The results showed that the bat TRIM family contains 70 members, with 24 under positive selection and 7 duplicated. Additional transcriptomic analysis revealed the tissue-specific expressions of TRIM9, 46, 54, 55, 63, and 72. Additionally, following interferon or viral stimulation, TRIM orthologs associated with antiviral immunity reported in humans were also upregulated in bat cells. The present study systematically analyzed the composition, evolution, and expression of bat TRIM genes. It may provide a theoretical basis for studies of bat TRIM in the fields of antiviral immunity, longevity, and tolerance to DNA damage.
With the birth of next-generation sequencing (NGS) technology, genomic data in public databases have increased exponentially. Unfortunately, exogenous contamination or intracellular parasite sequences in assemblies could confuse genomic analysis. Meanwhile, they can provide a valuable resource for studies of host-microbe interactions. Here, we used a strategy based on DNA barcodes to scan protistan contamination in the GenBank WGS/TSA database. The results showed a total of 13,952 metazoan/animal assemblies in GenBank, where 17,036 contigs were found to be protistan contaminants in 1507 assemblies (10.8%), with even higher contamination rates in taxa of Cnidaria (150/281), Crustacea (237/480), and Mollusca (107/410). Taxonomic analysis of the protists derived from these contigs showed variations in abundance and evenness of protistan contamination across different metazoan taxa, reflecting host preferences of Apicomplexa, Ciliophora, Oomycota and Symbiodiniaceae for mammals and birds, Crustacea, insects, and Cnidaria, respectively. Finally, mitochondrial proteins COX1 and CYTB were predicted from these contigs, and the phylogenetic analysis corroborated the protistan origination and heterogeneous distribution of the contaminated contigs. Overall, in this study, we conducted a large-scale scan of protistan contaminant in genomic resources, and the protistan sequences detected will help uncover the protist diversity and relationships of these picoeukaryotes with Metazoa.
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