GALNT2 is Required to Control respiratory Viral Infections
Speaker: Prof. Jincun Zhao, Professor, Guangzhou Institute of Respiratory Health, Guangzhou Medical University/ Director, State Key Laboratory of Respiratory Disease/ Assistant director, Guangzhou Laboratory
Date & Time: 30 May 2023, 16:30-17:30
Venue: Seminar Room 1 (Room 302, 3 Sassoon Road)
Prof. Zhao received his PhD from Peking University, Beijing, P.R. China. Prof. Zhao’s lab is focusing on the relationship between virus replication in the infected host and the immune response to the virus. Prof. Zhao especially interested in how the host response to coronaviruses cause immunopathological disease. Prof. Zhao has studied coronaviruses, with an emphasis on pathogenesis, for 20 years, with more than 160 publications. Prof. Zhao has a special interest in infections caused by MERS-CoV, SARS-CoV and SARS-CoV-2. Prof. Zhao has extensive experience analyzing virus-host interaction and innate and adaptive immune responses in coronavirus-infected mice and humans.
Interferon-stimulated genes (ISG) are important for restricting respiratory virus replications. To identify novel effective antiviral ISG, using transcriptomic profiling of wt versus ifnar-/- mice infected with SARS-CoV-2 in combination with single-cell RNA sequencing profiling from COVID-19 patients, we found that O-GalNAc transferases 2 (GALNT2) contributed to viral clearance and reduced disease severity. Further, we identified that GALNT2 is a novel ISG controlling coronaviruses (CoVs) and influenza A viruses (IAVs) replication in vitro and in vivo. Mechanistic analysis revealed that O-linked glycosylation of cleavage sites in the surface proteins of CoVs and IAVs by GALNT2 regulates viral activation, assembly and egress. These results provide experimental evidence for the crucial role of the GALNT2-based broad-spectrum antiviral defense in controlling respiratory virus infections.
CD4+ T cells select unique P65, IRF1 and FOS dependent responses in APC for integration into antiviral CD8+ T cell immunity
Speaker: Professor Sammy Bedoui, MD, Director of Research, School of Biomedical Sciences, Faculty of Medicine, Dentistry & Health Sciences, The Doherty Institute for Infection and Immunity at the University of Melbourne
Date & Time: 19 Apr 2023, 10:30-11:15
Sammy holds a medical degree from the Hannover Medical School in Germany and heads a laboratory at the Doherty Institute for Infection and Immunity in Melbourne, having previously held positions at the Walter & Eliza Hall Institute in Melbourne, the National Institute of Neuroscience in Tokyo and the Hannover Medical School in Germany. Sammy’s research seeks to advance our understanding of how immune responses are initiated, tailored to the specific conditions associated with a given infections or disease, and eventually tuned down when the initial threat is overcome. While his work focusses on the fundamental underlying principles, ongoing efforts seek to apply these insights to the development of better therapies against infections and cancer.
Antiviral CD8+ T cell immunity depends on the integration of varying contextual cues, but how antigen presenting cells (APC) consolidate these signals for decoding by T cells remains unclear. We describe gradual IFN-α/β-induced transcriptional adaptations that endowed APC with the capacity to rapidly activate the transcriptional regulators P65, IRF1 and FOS upon CD4+ T cell-mediated CD40 stimulation. While these responses operated through broadly utilized signaling components, they induced a unique set of costimulatory molecules and soluble mediators that could not be elicited by IFN-α/β or CD40 alone. This response was critical for the acquisition of antiviral CD8+ T cell effector function, and its activity in APC from patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) correlated with milder disease. These observations uncover a sequential integration process whereby APC rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.
Nowcasting COVID-19 epidemics in Hong Kong and Beijing
Speaker: Dr. Kathy Leung, Assistant Professor, WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, LKS Faculty of Medicine, HKU
Date & Time: 19 Apr 2023, 11:15-12:00
Kathy Leung received her PhD from School of Public Health at The University of Hong Kong. In recent years, Kathy is interested in mathematical modelling of a wide range of diseases such as influenza, RSV, MERS, COVID-19, hand-foot-and-mouth disease, HPV, cervical cancer, colorectal cancer, and breast cancer. She also conducts epidemiological and economic evaluations of disease intervention strategies, such as HMFD vaccination, public health and social measures against COVID-19, and risk-based breast cancer screening. Leveraged on the latest development of data science, she also participates in the development of tools to tackle misinformation about COVID-19 and HPV vaccination with AI language models. Kathy is a member of HKU’s COVID-19 Response Team and has contributed to the earliest studies about COVID-19 epidemiology. She is also an investigator of Programme 1 of the Laboratory of Data Discovery for Health (D²4H) at the Hong Kong Science Park.
Diverse patterns of COVID-19 epidemics have been observed in populations with varied social demographics, vaccination coverages, past waves of outbreaks and public health and social measures (PHSMs) implemented in response. We discussed how nowcasting of the Omicron epidemics has been enhanced during January to August 2022 in Hong Kong by integrating evolving data streams that gradually became available and implemented the model in the nowcasting of Beijing’s Omicron BF.7 epidemics in November 2022 to January 2023. We showed that epidemic nowcasting is a useful tool if the model is parameterised with sufficient data. Our framework provides a way to integrate multiple streams of epidemiological data and knowledge for short-term assessment of the epidemic scale and disease burden.
Interpreting the evolution of SARS-CoV-2
Speaker: Prof. Jesse D Bloom, Professor, Fred Hutch Cancer Research Center/ Affiliate Professor, Genome Sciences & Microbiology, University of Washington/ Investigator, Howard Hughes Medical Institute
Date & Time: 16 Feb 2023, 11:00-11:45
Prof. Bloom will discuss the long-term evolutionary patterns of human coronaviruses and how these relate to the evolution of SARS-CoV-2 in the last three years. I will also discuss new deep mutational scanning tools that can be used to interpret and to some degree forecast SARS-CoV-2 evolution.
SARS-CoV-2 and stability on interior surfaces of aircraft
Speaker: Prof. John M Nicholls, Clinical Professor, Department of Pathology, School of Clinical Medicine, HKU
Date & Time: (HKT) 16 Feb 2023, 11:45-12:30
The SARS-CoV-2 virus emerged in China in late 2019, and within 3 months had spread to most countries in the world. Early in the 2020 outbreak there was concern over the role of fomites and fecal-oral route of transmission as viral RNA was detected in the stools of infected patients (similar to that documented in the 2003 outbreak). In order to investigate the role of fomites or surfaces in the transmission of SARS-CoV-2 a number of laboratory based studies were performed in early 2020 which showed that after inoculation of a number of inanimate surfaces, virus could be cultured for periods up to 7 days, depending on the type of material. In view of these findings, numerous procedures were undertaken to mitigate spread, and particular attention was given to the commercial aviation industry, as historical date from the 2003 SARS outbreak showed that transmission could occur in the aircraft interior. Since considerable manpower and financial resources were being spent on surface transmission mitigation strategies, a laboratory investigation on SARS-CoV-2 survival on aircraft interior surfaces was considered an area worth investigation.
In this project we investigated stability over a 24-hour period using the major strains of SARS-CoV-2 on selected passenger high contact areas, as well as the effect of surface decontamination. We found that on most untreated surfaces viability dropped by 90 percent over 4 hours, and little culturable virus was present after 24 hours. Surface decontamination decreased virus survival, but the benefit was ameliorated by regular use and regular cleaning procedures. 3 years into the pandemic the role of fomite spread appears to have had only a minimal effect on virus transmission, especially in the aircraft environment.
Genomic epidemiology and phylodynamics of SARS-CoV-2 and other human respiratory viruses
Speaker: Dr. Vijaykrishna Dhanasekaran, Associate Professor, School of Public Health, HKU
Date & Time: 19 Dec 2022, 15:00-15:45
Abstract: An interplay between virus, host and ecological factors determines the incidence and evolution of human respiratory viruses, such as influenza, RSV, and, more recently, SARS-CoV-2. However, non-pharmaceutical interventions targeting COVID-19 have affected all respiratory viruses impacting future circulation patterns. This talk will discuss the application of genomic epidemiology and phylodynamics in Hong Kong to elucidate the changing dynamics of SARS-CoV-2 and other human respiratory viruses. Lastly, in light of the persistence of enhanced virus control measures in Hong Kong and mainland China, this talk will offer a perspective on the circulation patterns of key respiratory viruses over the long and short terms.
Epidemiology and estimation of time-varying transmission heterogeneity of SARS and COVID-19 in Hong Kong.
Speaker: Dr. Dillon Charles Adam, Research Assistant Professor, School of Public Health, HKU
Date & Time: (HKT) 19 Dec 2022, 15:45-16:30
Abstract: Heterogeneous transmission (aka superspreading) is a notable feature of the severe acute respiratory syndrome (SARS) and coronavirus disease 2019 (COVID-19) epidemics though previous efforts to estimate how estimates of heterogeneity change over time are limited. Using empirical offspring distributions generated from contact tracing data, we compared outbreaks of SARS and COVID-19 infection in Hong Kong to infer how measures of transmission heterogeneity changed over time and in response to non-pharmaceutical interventions (NPIs). We found that, surprisingly, measures of heterogeneity increased as chains of transmission were broken and the stringency of NPIs increased. This raises concerns when estimating heterogeneity from contact tracing data because estimates are potentially biased by the time and window of data collection, especially during ongoing epidemics. Time-varying or real-time estimates of transmission heterogeneity could become a complementary indicator for epidemic intelligence alongside Rt to support epidemic response.
SARS-CoV-2 immunity: T cells and antibody breadth by age and vaccine type
Date & Time: (HKT) 27 Oct 2022, 15:00-15:45
Abstract: The pandemic offers a unique opportunity to identify immune correlates of protection from infection and vaccination against COVID-19. Anti-Spike and Nucleocapsid based tests dominate COVID-19 serology in an increasingly immune population. Neutralising antibodies are a frontline defence but S and N specific FcR function can determine COVID-19 outcomes, whilst non-surface proteins such as ORF8 can mediate their action by FcR interactions and be used to discriminate infection status. Spike only vaccines and whole inactivated vaccines have vast differences in neutralizing antibody titers yet both protect against severe disease with most variants of concern. We therefore assessed the quality of the SARS-CoV-2 specific antibody response in terms of magnitude, breadth, avidity and FcR binding in various immune conditions including: children, time post infection and vaccinees (mRNA BNT162b2 versus inactivated virion Coronavac vaccines). Furthermore, vaccine responses were compared for booster doses and in adolescents. Whilst children had reduced immunity to SARS-CoV-2 infection than adults, adolescents made comparable vaccine responses. T cell responses were mostly driven by vaccine priming type rather than booster dose, whereas antibody responses, including breadth against VoC and Sarbecoviruses were shaped by recent booster vaccine type or prior exposure. These studies provide novel insights for vaccine platforms and SARS-CoV-2 immunogenicity to identify key targets for specific diagnostics and vaccine strategies.
Rapid identification of SARS-CoV-2 variants of concern using genomic surveillance data
Speaker: Dr. Ahmed Abdul QUADEER, Research Assistant Professor, Department of Electronic and Computer Engineering, HKUST
Date & Time: (HKT) 27 Oct 2022, 15:45-16:30
Abstract: This talk will describe how we used computational modelling and analysis of genomic sequence data to provide insights into different questions related to SARS-CoV-2 transmission, immune response, and vaccine design. The focus of the talk will be on our recently developed analytical epidemiological model that infers the transmission effects of mutations from genomic surveillance data. Applying our model to SARS-CoV-2 identifies multiple mutations that strongly affect the transmission rate, both within and outside the Spike protein. Importantly, the model detects lineages with increased transmission even at low frequencies. We rapidly infer signiﬁcant transmission advantages for the Alpha, Delta, and Omicron variants after their appearances in regional data, when their regional frequencies were only around 1-2%. Our model thus enables rapid identification of variants with enhanced transmission.
SARS-CoV-2 infection expedites cigarette smoke-exposed cell damage in primary human airway epithelial cells
Speaker: Dr. Judith C.W. Mak, Principal Lecturer, Department of Pharmacology and Pharmacy, The University of Hong Kong
Date & Time: (HKT) 26 Aug 2022, 14:30-15:00
Abstract: In the ongoing COVID-19 pandemic caused by SARS-CoV-2 infection, many countries across the world are struggling with the health crisis. Given the broad spectrum of COVID-19 clinical symptoms, muco-obstructive lung diseases like smoking-related COPD are typically associated with higher risk of COVID-19 severity. It is critical to elucidate the role of cigarette smoking on airway epithelial cell damage, leading to severe clinical outcome. Using electron microscopy, immunohistochemistry and gene expression analyses, this study provides evidence that exposure to cigarette smoking may upregulate the long form angiotensin converting enzyme (ACE)2 as binding receptor for SARS-CoV-2 and transmembrane serine proteases TMPRSS2/4 to help the viral entry, leading to an aggravated host immune response via inhibition of type I interferon pathway. Cigarette smoking may also worsen SARS-CoV-2-infected airway epithelial cell damage through junctional disruption, mucus hypersecretion and severe motile ciliary disorder. Therefore, this study has greatly increased our understanding of airway epithelial cell damage after SARS-CoV-2 infection in smokers.
Drug Discovery for Coronavirus Infections
Speaker: Dr. NG Wai-Lung Billy, Assistant Professor, School of Pharmacy, The Chinese University of Hong Kong
Date & Time: (HKT) 26 Aug 2022, 15:00-15:30
Abstract: The outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global threat to human health. Using in vitro screening and biochemical characterization, we identified the hepatitis C virus (HCV) protease inhibitor simeprevir as an especially promising repurposable drug for treating COVID-19. Simeprevir potently reduces SARS-CoV-2 viral load by multiple orders of magnitude and synergizes with remdesivir in vitro. Mechanistically, we showed that simeprevir inhibits the main protease (Mpro) and unexpectedly the RNA-dependent RNA polymerase (RdRp). Our results thus reveal the viral protein targets of simeprevir, and provide preclinical rationale for the combination of simeprevir and remdesivir for the pharmacological management of COVID-19 patients.
Direct activation of vascular endothelial cells by SARS-CoV-2 in an ACE2-independent manner: implications for COVID-19 associated vascular dysfunction
Speaker: Dr. Kathy Lui, Associate Professor, Department of Chemical Pathology, The Chinese University of Hong Kong
Date & Time: (HKT) 30 June 2022, 15:30-16:00
Abstract: Despite that the lungs are the primary organ targeted by SARS-CoV-2, systemic endothelial inflammation and dysfunction is observed in patients with severe COVID-19 in particular, manifested by elevated endothelial injury markers, endotheliitis, and coagulopathy. To date, it remains controversial whether ACE2 contributes to endothelial dysfunction in COVID-19, and the direct causative mechanism of SARS-CoV-2-induced endotheliitis is still unclear. In this talk, we will review the clinical characteristics of COVID-19 associated endothelial dysfunction; and the likely pathological mechanisms underlying the disease with a particular focus on the direct role of SARS-CoV-2 in endothelial cells (ECs). In contrast to current belief, our recent work reports that human ECs barely express ACE2. By ectopically expressing ACE2 in human stem cell derived-ECs to model SARS-CoV-2 infection, we found that ACE2-deficient ECs are resistant to the infection but are more activated upon exposure to the virus compared to that of the ACE2-expressing ones. The virus directly induces endothelial activation by increasing monocyte adhesion, nitric oxide production, and enhanced phosphorylation of p38 mitogen-associated protein kinase (MAPK), NF-κB, and eNOS in ACE2-expressing and -deficient ECs. ACE2-deficient ECs respond to SARS-CoV-2 through toll-like receptor 4 (TLR4) as treatment with its antagonist inhibits p38 MAPK/NF-κB/interleukin-1β (IL-1β) activation after viral exposure. Genome-wide, single-cell RNA-seq analyses further confirm activation of the TLR4/MAPK14/RELA/IL-1β axis in circulating ECs of mild and severe COVID-19 patients, suggesting that circulating ECs could serve as biomarkers for indicating patients with endotheliitis. Together, our findings support a direct role for SARS-CoV-2 in mediating endothelial inflammation in an ACE2-independent manner even though human ECs are mostly ACE2-deficient.
Next-generation Sequencing and Sequence Analysis of COVID-19 in HK
Speaker: Dr. Haogao Gu , Post-doctoral Fellow, School of Public Health, The University of Hong Kong
Date & Time: (HKT) 30 June 2022, 16:00-16:30
Abstract: We sequenced more than 5,000 SARS-CoV-2 positive samples in HK during the pandemic. The genomic sequences provide valuable information for studying the transmission dynamics and virus evolution.