Biology subjects

Ge, X.-Y.

Publications and source records attributed to Ge, X.-Y..

7 recordsLinked to original sources

bioRxiv2025

Sustained cross-species transmission of gammacoronavirus in wild birds reveled by viral characterization in China

Gammacoronavirus ({gamma}-CoV) primarily infects poultry, wild birds, and marine mammals. The widespread distribution and circulation of {gamma}-CoV in the ecological environment may lead to sustained transmission and economic loss. To better understand the diversity of {gamma}-CoV in wild birds, we collect 482 wild-bird fecal samples from Yunnan, encompassing fourteen bird species. We detected twelve {gamma}-CoV positive samples in five bird species, with the characterization of five complete genomes - HNU5-1, HNU5-2, HNU5-3, HNU6-1, and HNU6-2-indicating that these genomes represent two viral species. The HNU5 strains were derived from Black-headed gull (Chroicocephalus ridibundus), while the HNU6 strains were came from Mallard (Anas platyrhynchos), and both of those were recombinant. The HNU5 strain exhibited the highest sequence identity (95.45%) with a {gamma}-CoV strain isolated from Numenius phaeopus (GenBank accession: PP845452). Similarly, the HNU6 strain showed 95.18% nucleotide identity with a {gamma}-CoV strain (GenBank accession: PP845437) derived from Anas platyrhynchos. Taxonomic analysis confirmed that HNU6s belong to the Gammacoronavirus anatis species, while HNU5s attributed to a new species. Cross-species analysis revealed active host-switching events among {gamma}-CoVs, indicating potential transmission of {gamma}-CoVs from marine mammals to wild bird, from wild bird to poultry, and inter-wild bird and inter-poultry transmission. In summary, we report five new {gamma}-CoV strains in wild birds and outline the cross-species transmission of {gamma}-CoVs. Our findings link {gamma}-CoV hosts across different natural environments and provide new insights for exploring {gamma}-CoVs.

microbiology↗

bioRxiv2023

Virome analysis provides new insights into the pathogenesis mechanism and treatment of SLE disease

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease. Many viruses have been reported to be associated with SLE, but the diversity of the virome in SLE and the mechanisms underlying the interactions between viral infection and SLE are still unclear. This study identified ten human virus species from 826 RNA-Seq samples of human blood from 688 SLE patients and 138 healthy controls. SLE patients were found to have higher positive rates of viruses than healthy controls, although the virus abundances were low and comparable in both SLE patients and healthy controls. Analysis of the antiviral interferon-stimulated genes (ISGs) in samples showed higher ISG expression levels in virus-positive samples compared to virus-negative samples, which confirmed viral infections in virus-positive samples. Further analysis of differential expression genes between virus-positive and negative SLE patients showed that several genes that were up-regulated in SLE patients were further up-regulated after viral infections, and they were mainly enriched in immune response-related biological processes, suggesting an excess immune response in SLE patients after viral infections. Finally, three marker genes of the SLE severity, namely STAT1, STAT5A, and STAT5B, showed higher expression levels in virus-positive SLE patients compared to those in virus-negative SLE patients, suggesting that viral infections may aggravate the SLE disease. Overall, the study deepens our understanding of the association between viruses and SLE and provides new insights into prevention and control of the disease.

bioinformatics↗

bioRxiv2022

Key mutations on spike protein altering ACE2 receptor utilization and potentially expanding host range of emerging SARS-CoV-2 variants

Increasing evidence supports inter-species transmission of SARS-CoV-2 variants from human to domestic or wild animals during the ongoing COVID-19 pandemic, which is posing great challenges to epidemic control. Clarifying the host range of emerging SARS-CoV-2 variants will provide instructive information for the containment of viral spillover. The spike protein (S) of SARS-CoV-2 is the key determinant of receptor utilization, and therefore amino acid mutations on S will probably alter viral host range. Here, in order to evaluate the impact of S mutations, we constructed 20 Hela cell lines stably expressing ACE2 orthologs from different animals, and prepared 27 pseudotyped SARS-CoV-2 carrying different spike mutants, among which 20 bear single mutation and the other 7 were cloned from emerging SARS-CoV-2 variants, including D614G, Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), Delta (B.1.135), Lambda (B.1.429) and Mu (B.1.525). Using pseudoviral reporter assay, we identified that the substitutions of T478I and N501Y enabled the pseudovirus to utilize chicken ACE2, indicating potential infectivity to avian species. Furthermore, the S mutants of real SARS-CoV-2 variants comprising N501Y showed significantly acquired abilities to infect cells expressing mouse ACE2, indicating a critical role of N501Y in expanding SARS-CoV-2 host range. In addition, A262S and T478I significantly enhanced the utilization of various mammals ACE2. In summary, our results indicated that T478I and N501Y substitutions were two S mutations important for receptor adaption of SARS-CoV-2, potentially contributing to spillover of the virus to many other animal hosts. Therefore, more attention should be paid to SARS-CoV-2 variants with these two mutations.

microbiology↗

bioRxiv2021

m6A-mediated Cell-cell Communication Controls Planarian Regeneration

Regeneration is the regrowth of damaged tissues or organs, a vital mechanism responding to damages from primitive organisms to higher mammals. Planarian possesses active whole-body regenerative capability owning to its vast reservoir of adult stem cells, neoblasts, thus provides an ideal model to delineate the underlying mechanisms for regeneration. N6-methyladenosine (m6A) regulates stem cell renewal and differentiation. However, how m6A controls regeneration at whole-organism level remains largely unknown. Here, we demonstrate that the depletion of m6A methyltransferase regulatory subunit wtap abolishes planarian regeneration, through regulating cell-cell communication and cell cycle. scRNA-Seq analysis unveils that the wtap knockdown induces a unique type of neural progenitor-like cells (NP-like cells), characterized by specific expression of the cell-cell communication ligand grn. Intriguingly, the depletion of m6A-modified transcripts grn/cdk9 (or cdk7) axis rescues the defective regeneration of planarian without wtap. Overall, our study reveals an indispensable role of m6A-dependent cell-cell communication essential for whole-organism regeneration.

molecular biology↗

bioRxiv2020

Autonomous sensing the insulin peptide by an olfactory G protein coupled receptor modulates glucose metabolism

Along with functionally intact insulin, diabetes-associated insulin peptides are secreted by {beta} cells(1-3). By screening the expression and functional characterization of olfactory receptors in pancreatic islets, we identified Olfr109 as the receptor to detect insulin peptides. Engagement of one insulin peptide, insB:9-23, with Olfr109 diminished insulin secretion through Gi-cAMP signalling and promoted macrophage proliferation. Remarkably, Olfr109 deficiency alleviated intra-islet inflammatory responses and improved glucose homeostasis in Akita- and HFD-fed mice. We further determined the binding mode between the insB:9-23 and Olfr109. A pepducin-based Olfr109 antagonist improved glucose homeostasis in diabetic and obese mouse models. Collectively, we found that pancreatic {beta} cells use Olfr109 to autonomously detect self-secreted insulin peptides and this detection arrests insulin secretion and crosstalk with macrophages to increase intra-islet inflammation.

physiology↗

bioRxiv2020

Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV

Coronavirus pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, SARS-CoV caused SARS pandemic in 2003 and SARS-CoV-2 caused the COVID-19 pandemic recently. Both viruses have been reported to originate from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20th and 42nd amino acids that may determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies promote the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.

microbiology↗

bioRxiv2020

Characterization of the substitution hotspots in SARS-CoV-2 genome using BioAider and detection of a SR-rich region in N protein providing further evidence of its animal origin

The novel human coronavirus (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19) pandemic worldwide. The increasing sequencing data have shown abundant single nucleotide variations in SARS-CoV-2 genome. However, it is difficult to quickly analyze genomic variation and screen key mutations of SARS-CoV-2. In this study, we developed a visual program, named BioAider, for quick and convenient sequence annotation and mutation analysis on multiple genome-sequencing data. Using BioAider, we conducted a comprehensive genome variation analysis on 3,240 sequences of SARS-CoV-2 genome. Herein, we detected 14 substitution hotspots within SARS-CoV-2 genome, including 10 non-synonymous and 4 synonymous ones. Among these hotspots, NSP13-Y541C was predicted to be a crucial substitution which might affect the unwinding activity of NSP13, a key protein for viral replication. Besides, we also found 3 groups of potentially linked substitution hotspots which were worth further study. In particular, we discovered a SR-rich region (aa 184-204) on the N protein of SARS-CoV-2 distinct from SARS-CoV, indicating more complex replication mechanism and unique N-M interaction of SARS-CoV-2. Interestingly, the quantity of SRXX repeat fragments in the SR-rich region well reflected the evolutionary relationship among SARS-CoV-2 and SARS-CoV-2 related animal coronaviruses, providing further evidence of its animal origin. Overall, we developed an efficient tool for rapid identification of mutations, identified substitution hotspots in SARS-CoV-2 genomes, and detected a distinctive polymorphism SR-rich region in N protein. This tool and the detected hotspots could facilitate the viral genomic study and may contribute for screening antiviral target sites.

genomics↗