A5003298311- Immune Cell Function and Interaction
- HIV Research and Treatment
- CAR-T cell therapy research
- Influenza Virus Research Studies
- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- SARS-CoV-2 and COVID-19 Research
- HIV/AIDS drug development and treatment
- vaccines and immunoinformatics approaches
- Monoclonal and Polyclonal Antibodies Research
- Pancreatic and Hepatic Oncology Research
- Respiratory viral infections research
- T-cell and B-cell Immunology
- COVID-19 Clinical Research Studies
- HIV/AIDS Research and Interventions
- interferon and immune responses
- Immune Response and Inflammation
- Virus-based gene therapy research
- Hepatitis B Virus Studies
- MicroRNA in disease regulation
- Herpesvirus Infections and Treatments
- Cancer-related molecular mechanisms research
- Animal Virus Infections Studies
- Animal Disease Management and Epidemiology
- Hepatitis C virus research
Shanghai Public Health Clinical Center
2016-2025
Fudan University
2014-2025
Zhongshan Hospital
2021-2025
Sun Yat-sen University
2016-2025
Zhongshan Hospital of Xiamen University
2023-2025
Nanchang University
2017-2025
The First Affiliated Hospital, Sun Yat-sen University
2016-2025
Guangzhou University of Chinese Medicine
2025
Beijing Obstetrics and Gynecology Hospital
2023-2025
Capital Medical University
2023-2025
Abstract Coronavirus disease 2019 (COVID-19), caused by the novel human coronavirus SARS-CoV-2, is currently a major threat to public health worldwide. The viral spike protein binds host receptor angiotensin-converting enzyme 2 (ACE2) via receptor-binding domain (RBD), and thus believed be target block entry. Both SARS-CoV-2 SARS-CoV share this mechanism. Here we functionally analyzed key amino acid residues located within binding motif of RBD that may interact with ACE2 available...
The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction high-resolution design of proteins, nucleic acids, a growing number non-natural polymers. Despite its free availability to academic users improving documentation, use has largely remained confined developers their immediate collaborators due code's difficulty use, requirement large computational resources, unavailability servers most applications. Here, we...
Significance A unique avian-origin H7N9 influenza virus caused 134 human infections with 44 deaths. The host factors contributing to moderate vs. severe disease are not clear. Here, we show that severity was associated a higher level of cytokines/chemokines. We demonstrate the cytokines in infected lung were 100- 1,000-fold than those plasma. Furthermore, found IFN-induced transmembrane protein-3 (IFITM3) C/C genotype clinical outcome, as reflected by reduced time seeking medical aid; more...
Abstract The avian origin A/H7N9 influenza virus causes high admission rates (>99%) and mortality (>30%), with ultimately favourable outcomes ranging from rapid recovery to prolonged hospitalization. Using a multicolour assay for monitoring adaptive innate immunity, here we dissect the kinetic emergence of different effector mechanisms across spectrum H7N9 disease recovery. We find that diversity response contribute resolution survival. Patients discharged within 2–3 weeks have early...
Mucosal-associated invariant T (MAIT) cells are innate-like lymphocytes known to elicit potent immunity a broad range of bacteria, mainly via the rapid production inflammatory cytokines. Whether MAIT contribute antiviral is less clear. Here we asked whether produce cytokines/chemokines during severe human influenza virus infection. Our analysis in patients hospitalized with avian H7N9 pneumonia showed that individuals who recovered had higher numbers CD161(+)Vα7.2(+) peripheral blood...
Abstract In response to infections and irritants, the respiratory epithelium releases alarmin interleukin (IL)-33 elicit a rapid immune response. However, little is known about regulation of IL-33 following its release. Here we report that biological activity at receptor ST2 rapidly terminated in extracellular environment by formation two disulphide bridges, resulting an extensive conformational change disrupts binding site. Both reduced (active) bonded (inactive) forms can be detected lung...
Most patients with severe infection influenza A virus (IAV) progress to acute respiratory distress syndrome and even multiple organ dysfunction (MODS). Neutrophil extracellular traps (NETs) can be induced by pathogens are responsible for immune tissue damage. We conducted a prospective study on the production effects of NETs in H7N9 H1N1 patients. investigated NET plasma supernatant cultured neutrophils measuring cell-free deoxyribonucleic acid (DNA) myeloperoxidase (MPO)-DNA complexes...
Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We purified more than 1,000 memory B cells specific SARS-CoV-2 S1 or its RBD (receptor binding domain) obtain 729 paired heavy- light-chain fragments. Among these, 178 test positive for antigen binding, the majority of top 17 binders with EC50 below 1 nM are binders. Furthermore, we identify 11 antibodies, eight which show IC50 within 10 nM, best one, 414-1,...
Host cellular receptors play key roles in the determination of virus tropism and pathogenesis. However, little is known about SARS-CoV-2 host with exception ACE2. Furthermore, ACE2 alone cannot explain multi-organ nor clinical differences between SARS-CoV, suggesting involvement other receptor(s). Here, we performed genomic receptor profiling to screen 5054 human membrane proteins individually for interaction capsid spike (S) protein. Twelve proteins, including ACE2, ASGR1, KREMEN1, were...
Abstract Despite prolonged surveillance and interventions, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) influenza viruses continue to pose a global health burden. Thus, we developed chimpanzee adenovirus-based combination vaccine, AdC68-HATRBD, with dual specificity against SARS-CoV-2 virus. When used as standalone intranasal immunization AdC68-HATRBD induced comprehensive potent immune responses consisting of immunoglobin (Ig) G, mucosal IgA, neutralizing antibodies,...
T cells develop functional defects during HIV-1 infection, partially due to the upregulation of inhibitory receptors such as programmed death-1 (PD-1) and CTLA-4. However, role lymphocyte activation gene-3 (LAG-3; CD223), also known an receptor, in HIV infection remains be determined. In this study, we revealed that LAG-3 on delivers signal downregulate cell functionality, thereby playing immunoregulatory persistent infection. We observed results a significant increase expression both...
Abstract Severe influenza A virus (IAV) infection is associated with immune dysfunction. Here, we show circulating CD8 + T-cell profiles from patients hospitalized avian H7N9, seasonal IAV, and vaccinees. Patient survival reflects an early, transient prevalence of highly activated CD38 HLA-DR PD-1 T cells, whereas the prolonged persistence this set found in ultimately fatal cases. Single-cell cell receptor (TCR)-αβ analyses cells similar TCRαβ diversity but differential clonal expansion...
Antibody Modeling Assessment II (AMA-II) provided an opportunity to benchmark RosettaAntibody on a set of 11 unpublished antibody structures. produced accurate, physically realistic models, with all framework regions and 42 the 55 non-H3 CDR loops predicted under Ångström. The performance is notable when modeling H3 homology framework, where best model among participants for four targets, two which were sub-Ångström accuracy. To improve RosettaAntibody, we pursued causes errors. most common...
Abstract Background The receptor-binding domain (RBD) variants of SARS-CoV-2 could impair antibody-mediated neutralization the virus by host immunity; thus, prospective surveillance antibody escape mutants and understanding evolution RBD are urgently needed. Methods Using single B cell cloning technology, we isolated characterized 93 RBD-specific antibodies from memory cells four COVID-19 convalescent individuals in early stage pandemic. Then, global alanine scanning with a panel 19 selected...
Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown presence intracellular virus particles human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if might receptors other than ACE2...
Non-alcoholic fatty liver disease (NAFLD) is a prevalent disorder strongly associated with metabolic dysfunction, particularly in elderly populations where it presents higher prevalence and severity. This study aimed to investigate the association between serum uric acid (SUA) levels NAFLD older adults, focusing on independent effect of hyperuricemia risk. We enrolled 469 individuals aged ≥ 65 years who underwent community health checkups. The exposure variable was baseline SUA levels, while...