Speaker
Speakers
Prof Honglin Chen
Prof Zhiwei Chen
Prof Kelvin KW To
Prof Pengtao Liu
Dr Jasper FW Chan
Dr Hin Chu
Dr Shuofeng Yuan
Abstracts for Oral Presentation
Name & Affiliation:
Prof Stanley Perlman
The University of Iowa
Title: How SARS-CoV-2 Evades Neutralizing Antibodies and Antiviral Drugs
Abstract:
Loss of olfactory function has been commonly reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections. Anosmia is not well understood. Previous studies showed that sustentacular cells, and occasionally, olfactory sensory neurons (OSNs) in the olfactory epithelium (OE) are infected in SARS-CoV-2-infected patients and experimental animals. Here, we show that SARS-CoV-2 infection of sustentacular cells induces inflammation characterized by infiltration of myeloid cells to the olfactory epithelium and variably increased expression of proinflammatory cytokines. We observed widespread damage to, and loss of cilia on, OSNs, accompanied by downregulation of olfactory receptors and signal transduction molecules involved in olfaction. A consequence of OSN dysfunction was a reduction in the number of neurons in the olfactory bulb expressing tyrosine hydroxylase, consistent with reduced synaptic input. We also identified long term behavioral defects in SARS-CoV-2 infected mice, and changes in gene expression in the substantia nigra, an area of the brain affected in Parkinson’s Disease. Together, these results begin to define the downstream effects of sustentacular cell infection, provide insight into olfactory dysfunction in COVID-19-associated anosmia and identify neurological defects in infected mice.
In a second project, SARS-CoV-2 infected patients and mice develop neutrophilia, and this is correlated with worse outcomes. We show that a single chemokine, CXCL12, is increased in people and mice with neutrophilia. Unexpectedly, CXCL12 levels are inversely correlated with neutrophilia, identifying a potential therapeutic target.
Biography:
Dr Perlman received his Ph.D. in Biophysics from M.I.T., Cambridge, Massachusetts and his M.D. from the University of Miami, Miami, Florida. He was trained in Pediatrics and Pediatric Infectious Diseases at Boston Children’s Hospital, Boston, Massachusetts. He is a member of the VRBPAC of the FDA and the COVID-19 Advisory Committee of the ACIP (Advisory Committee on Immunization Practices). His current research efforts are focused on coronavirus pathogenesis, including virus- induced demyelination and the Severe Acute Respiratory Syndrome (SARS), the Middle East Respiratory Syndrome (MERS) and COVID-19. His laboratory has developed several novel animal models useful for studying pathogenesis and evaluating vaccines and anti-viral therapies. His studies are directed at understanding why aged patients and mice developed more severe disease than younger individuals after infection with SARS-CoV or SARS-CoV-2. His laboratory has developed several mouse models for COVID-19. Among other topics, his research is now focusing on the loss of sense of smell (anosmia) and taste (ageusia) and neurological disease in patients with acute SARS- CoV-2 infection and PASC (Post Acute Sequelae of COVID-19).
Name & Affiliation:
Prof Susan Weiss
University of Pennsylvania
Title: IFN responses are critical for control of human coronavirus infection in the nasal epithelium
Abstract:
All respiratory viruses establish a primary infection in the nasal epithelium, where efficient induction of antiviral innate immune responses may result in local control of viral replication, limited spread to the lower airway, and minimal pathogenesis. To study the role of antiviral interferon (IFN) signaling during infection, we utilize a primary epithelial culture system in which patient-derived sinonasal epithelial cells are grown at an air-liquid interface (ALI). Nasal ALI cultures recapitulate the polarized heterogeneous cellular population and mucociliary functions of the in vivo airway. We performed RNA seq analyses of nasal ALI cultures infected with 4 human coronaviruses (HCoVs) and found that these HCoVs diverged significantly in terms of antiviral IFN induction. MERS-CoV showed near complete shut- down of IFN signaling, SARS-CoV-2 showed moderate IFN induction, and the common cold-associated HCoVs (HCoV-229E and HCoV-NL63) showed the strongest IFN signature. Infections with MERS-CoV or SARS-CoV-2 mutant recombinant viruses defective in IFN antagonists reverse its IFN-evasive phenotype, resulting in IFN induction similar to the seasonal HCoVs. We further carried out nasal cell infections with each of these HCoVs in the presence of ruxolitinib, a JAK (Janus kinase) inhibitor, which abrogates IFN signaling. While ruxolitinib treatment has minimal impact on viral titers at early time points, titers are increased significantly at later time points, with the most significant impact of ruxolitinib during seasonal HCoV infection (titers 2-3 log10 PFU/mL increased late in infection). These data indicate that induction of antiviral IFN signaling in the nasal epithelium may be pivotal in clearance or resolution of HCoV infection, especially during infections with HCoVs that replicate predominantly in the upper respiratory tract.
Biography:
Susan Weiss obtained her PhD in Microbiology from Harvard University working on paramyxoviruses and did postdoctoral training in retroviruses at University of California, San Francisco. She came to the University of Pennsylvania (Penn) as an Assistant Professor in 1980, and is currently Professor and Vice Chair, Department of Microbiology and Co-director of the Penn Center for Research on Coronaviruses and Other Emerging Pathogens at the Perelman School of Medicine at Penn. She previously served as Associate Dean for Biomedical Postdoc Programs (2010-2019). She has worked on many aspects of coronavirus replication and pathogenesis over the last forty years, making contributions to understanding the basic biology as well as viral entry, organ tropism and virulence. This work focused for many years on the murine coronavirus (MHV) mouse model of hepatitis. More recently she has work on SARS-CoV and MERS-CoV and since 2020 also on SARS-CoV-2, as well as the “common cold” coronaviruses. Her work for the last ten years has focused on coronavirus interaction with the host innate immune response, viral antagonists of double-stranded RNA induced antiviral pathways and interactions with the unfolded protein responses. Most recent work also focusses on coronavirus infection of the nasal epithelium, the earliest site of infection. Her other research interests include activation and antagonism of the double-stranded RNA induced antiviral responses, with a focus on the oligoadenylate-ribonuclease L (OAS-RNase L) pathway, flavivirus- primarily Zika-virus-host interactions and pathogenic effects of host endogenous dsRNA.
Name & Affiliation:
Prof Linfa Wang
National University of Singapore
Title: Bats, viruses and pandemics
Abstract:
In Chinese zodiac, 2020 was The Year of Rat (2020). However, bats featured more in that year due to COVID-19 pandemic and the association of SARS-CoV-2 related viruses with bats. In the last 25 years, we have had multiple zoonotic diseases outbreaks caused by bat- borne viruses or probable bat viruses: Hendra in Australia (first detected in 1994), Nipah in Malaysia/Singapore (1998/9), SARS outbreak (2002/3), MERS outbreak (2012), large scale Ebola virus outbreak (2014) and SARS-CoV-2 (2019/20).
In this presentation, I will discuss the lessons learnt from studying bat-borne emerging zoonotic viruses and bat immunology in the context of better preparing for future pandemics and translating “bat knowledge” into improving human health in general.
Biography:
Linfa Wang is a professor of the Programme in Emerging Infectious Diseases at Duke-NUS Medical School, and the inaugural executive director of PREPARE, Ministry of Health, Singapore. He is an international leader in the field of emerging zoonotic viruses and virus- host interaction. His current research focuses on why bats are such an important reservoir for emerging viruses and on how we can learn from bats to make us more resilience to infection and diseases in general. Prof Wang has more than 500 scientific publications, including papers in Science, Nature, Cell, NEJM and Lancet. Prof Wang was elected to the Australian Academy of Technological Sciences and Engineering in 2010, the American Academy of Microbiology in 2021 and the Australian Academy of Sciences in 2023. He received the Singapore President Science Award in 2021.
Name & Affiliation:
Prof Zhengli Shi
Wuhan Institute of Virology, Chinese Academy of Sciences
Title: The entry pathway and pathogenicity study of bat SARS-related coronaviruses
Abstract:
In the past 20 years, two different strains of SARS-related coronaviruses (SARSr-CoV), SARS- CoV and SARS-CoV-2, caused pandemics. Both of them are considered to have a bat origin as the closely-related CoVs were discovered in bats. Bat SARSr-CoV are carried by different rhinolophus species which are only distributed in the Old World. Based on the conserved RNA-dependent RNA polymerase genes, SARSr-CoVs are divided into SARS-CoV-1 related viruses which are found in Africa, Europe and Asia, and SARS-CoV-2-related viruses which are only found in Asia. The major differences of these SARSr-CoV are located in the spike proteins which are responsible for virus entry and inducing the neutralization antibody. SARS-CoV-1 and -2 utilize the same receptor ACE2, while bat SARSr-CoVs can be divided into ACE2-dependent and-independent group. Some ACE2-dependent bat SARSr-CoVs have a high binding affinity to human ACE2 and efficiently infect human ACE2 transgenic mice showing different severity of lung damage. These results showed that some bat SARSr-CoVs have potential interspecies transmission and the countermeasures should be prepared in advance.
Biography:
Dr Shi is Director of the Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences and the Group leader for Emerging Virus Team. She focuses her research on pathogen investigation of unknown viruses in wild animals and interspecies infection mechanism of zoonotic viruses. She is in charge for the viral surveillance screening among bat samples leading to the discovery and new recognition of a wide-array of SARS-like coronaviruses, adenoviruses and adeno-associated viruses in mainland China. Her long experience on bat coronavirus led to the rapid identification of the pathogen of COVID-19 and its probable bat origin. Shi won the second prize of Natural Science Award of China in 2018 and was elected as fellowship of American Academy of Microbiology in 2019. She has provided editorial service to Virology, Virol J and has served since 2017 as Editor-in-Chief for Virologica Sinica.
Name & Affiliation:
Prof Jincun Zhao
Guangzhou Medical University
Title: T Cell Responses in Respiratory Coronavirus Infected Mice and Humans
Abstract:
Recently, the novel CoV SARS-CoV-2 caused severe COVID-19 pneumonia in human. Robust human to human transmission of SARS-CoV-2 has led to a pandemic worldwide. CoV- specific T cells have been identified both in CoV-infected mice and patients, including SARS- CoV, MERS-CoV and SARS-CoV-2. Here, we will summarize the T cell responses after CoV infection or vaccination, and their roles in protection of infected hosts.
Biography:
Prof Zhao’s lab is focusing on the relationship between virus replication in the infected host and the immune response to the virus. He is 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. He has a special interest in infections caused by MERS-CoV, SARS-CoV and SARS-CoV-2. He has extensive experience analyzing virus-host interaction and innate and adaptive immune responses in coronavirus-infected mice and humans.
Name & Affiliation:
Prof Chaoyong Yang
Xiamen University
Title: Dendrimeric DNA Coordinate Barcoding Design for Spatial RNA Sequencing
Abstract:
Infections are intricate and dynamic events involving interactions between pathogens and hosts. Spatially resolved transcriptomic technologies offer a valuable approach to investigate the complex spatial organization of cells, the diverse range of cell types involved, the variations in immune responses, and the intricate molecular mechanisms underlying infectious diseases. Recently, our team has developed Decoder-seq, a dendrimeric DNA coordinate barcoding design for spatial RNA sequencing. Decoder-seq combines dendrimeric nano-substrates with microfluidic coordinate barcoding to create high-density spatial DNA arrays with deterministic combinatorial barcodes, offering resolution flexibility and cost-effectiveness. Decoder-seq exhibits high RNA capture efficiency, approximately 68.9% of in situ sequencing, and enhances the detection of lowly expressed genes by approximately five-fold compared to 10× Visium. By applying Decoder-seq, we have visualized a spatial single-cell atlas of the mouse hippocampus at near-cellular resolution (15 μm) and identified mRNAs enriched in dendrites. When applied to renal cancers, Decoder-seq has unraveled the heterogeneous tumor microenvironment of two subtypes, revealing spatially gradient-expressed genes that hold potential for predicting tumor prognosis and progression. With its high sensitivity and near-single-cell resolution, Decoder-seq represents a powerful technology for investigating tissue-wide changes in molecular dynamics, signaling pathways, microenvironments, and cell-cell interactions, thereby facilitating the study of disease mechanisms, including those associated with infectious diseases.
Biography:
Prof Chaoyong Yang is a Distinguished Professor at Xiamen University and Vice-Director of Institute of Molecular Medicine, Shanghai Jiao Tong University. He received his PhD from University of Florida under the guidance of Professor Weihong Tan. After postdoc training in Professor Richard Mathies’ group at UC Berkeley, he joined Xiamen University in 2008. Professor Yang has published more than 300 research papers in international journals which have received over 16,000 citations. He coauthored 3 books and holds 65 patents. He is the associate editor of Analytical Chemistry and has served in the advisory board of 10 international journals. He is a Fellow of the Royal Society of Chemistry and senior member of Chinese Chemical Society. He received many awards including CAPA Distinguished Faculty Award in 2012, National Outstanding Young Investigator Award in 2013, Chinese Young Analyst Award in 2015, Chinese Chemical Society-Royal Society of Chemistry Young Chemist Award in 2016, and 2021 ACS Advances in Measurement Science Lectureship Award. His research focuses on the development of novel chemical and microfluidic tools for life science research and disease diagnosis, which integrates molecular engineering approaches, bio- nanotechnologies, and microfluidics to develop novel methods, smart materials, and functional miniaturized devices to address previously-intractable bioanalytical and biomedical problems.
Name & Affiliation:
Prof Pengtao Liu
The University of Hong Kong / Centre for Translational Stem Cell Biology
Title: Stem cell-derived trophoblasts for SARS-CoV study
Abstract:
By inhibiting signal pathways implicated in the earliest embryo development, we established cultures of mouse expanded potential stem cells (EPSCs) from individual 4-cell and 8-cell blastomeres, by direct conversion of embryonic stem cells (ESCs) and through reprogramming somatic cells. A single EPSC can contribute to both the embryo proper and the TE lineages in chimera assay. Bona fide trophoblast stem cell (TSC) lines, extra-embryonic endoderm stem (XEN) cells, and ESCs could be directly derived from EPSCs in vitro. Molecular analyses of the epigenome and single-cell transcriptome revealed that EPSCs had enriched features of cleavage stage embryos. The knowledge of mouse EPSCs has enabled the establishment of EPSCs of human, pig, bovine and additional mammalian species. EPSCs of these species share similar molecular features and have the potential to differentiate to extra-embryonic as well as embryonic cell lineages in vitro and in chimeras (animal EPSCs). They are genetically and epigenetically stable, can be maintained in homogenous long-term cultures and permit efficient precision genome editing. EPSCs thus provide new tools for studying normal development and open up new avenues for translational research in biotechnology, agriculture, and regenerative medicine. For example, we find that early syncytiotrophoblasts generated from human TSCs are highly susceptible to coronavirus infection and are sensitive to antiviral treatment. These findings may facilitate stem cell-based antiviral drug discovery. I will discuss our thoughts on collaborations with microbiologist colleagues.
Biography:
Professor Liu received his PhD from Baylor College of Medicine under the guidance of Professor Allan Bradley and completed his postdoctoral training at National Cancer Institute (USA) in the laboratories of Professor Neal Copeland and Professor Nancy Jenkins. Professor Liu joined The University of Hong Kong in September 2017 to be a full Professor at the School of Biomedical Sciences. Innovation and Technology Commission granted funding to Professor Liu in 2020 at Health@InnoHK initiative for the setup of Centre for Translational Stem Cell Biology, focusing on developing new stem cell technologies and applications for regenerative and genomic medicine.
Name & Affiliation:
Prof Honglin Chen
The University of Hong Kong / Centre for Virology, Vaccinology and Therapeutics
Title: Generation and Characterization of an influenza viral vector vaccine system for recurring and emerging respiratory
viral infections
Abstract:
Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal in preventing infection. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with a deleted NS1 gene that encodes cell surface expression of the receptor-binding-domain (RBD) of the SARS-CoV-2 spike protein. The DelNS1-RBD LAIV system has been evaluated in animal models and in humans for the control of SARS-CoV-2 infections. The molecular basis of immunogenicity of DelNS1 LAIV is studied. We showed that the DelNS1 LAIV is an unique vaccine system for creating dual function vaccines against both influenza and other respiratory viruses in annual vaccination strategies.
Biography:
Prof Honglin Chen finished his PhD study in Microbiology from the University of Hong Kong working on molecular biology of Epstein-Barr virus (EBV) in nasopharyngeal carcinoma (NPC). He continued his post-doctoral research on EBV at John Hopkins University School of Medicine. Prof. Chen re-joined Department of Microbiology, the University of Hong Kong in 2003 and has since expanded his research scopes to RNA viruses including emerging influenza viruses and coronaviruses. He has established several strong research programs and platform technologies which focus on studying molecular determinants for cross species transmission of avian influenza viruses and coronavirus. His research on influenza virus has led to important publications and the establishment of a unique DelNS1 live attenuated influenza vaccine system which has been used to develop vaccines for COVID- 19, and become an important technology for the pandemic preparedness of future emerging respiratory viral diseases.
Name & Affiliation:
Prof Zhiwei Chen
The University of Hong Kong / Centre for Virology, Vaccinology and Therapeutics
Title: Exceptional adaptability of B cell receptor for potent neutralizing antibodies against SARS- CoV-2 BA.4/5, BQ.1.1 and XBB1.5
Abstract:
Newly emerged SARS-CoV-2 subvariants BA.4/5, BQ.1.1 and XBB1.5 are highly resistant to all clinically approved neutralizing antibodies (NAbs) and prior vaccine/infection-induced neutralizing antibody responses. Here, we report a panel of broadly NAbs (bnAbs) arising from vaccine breakthrough infections. These bnAbs could neutralize all current SARS-CoV-2 variants of concern (VOCs) including subvariants BA.4/5, BQ.1.1 and XBB1.5 with exceptional potency of IC50 values less than 10 ng/mL, representing the best-in-class I/II bnAbs. Besides the well-known public antibody clonotype IGHV3-53/3-66, we found a rarely reported clonotype IGHV4-39/IGKV1-NL1 among them. Importantly, these bnAbs not only reduced infection significantly in hamsters intranasally challenged by BA.5.2, BQ.1.1 and XBB.1.5 but also prevent viral transmission through close contacts. The CryoEM analysis further revealed unique structural features of these bNAbs accommodating documented Omicron substitutions, leading to potent blockade of receptor ACE-2 binding. These results highlight the exceptional adaptability of human B cell receptor against emerging SARS-CoV- 2 variants.
Biography:
Prof Zhiwei Chen is the founding director of the AIDS Institute of the University of Hong Kong (HKU), which was established at HKU Li Ka Shing Faculty of Medicine in 2007. He is now a tenured full professor in the Department of Microbiology. In 1996, he finished his postgraduate studies with Prof. Preston A. Marx at the Aaron Diamond AIDS Research Center (ADARC) and obtained his Ph.D. degree from New York University School of Medicine in the USA. From 1996 to 2007, he was trained with Prof. David D. Ho and progressed from a post-doc to a research scientist, and then to a staff investigator/assistant professor at ADARC. In 2007, he joined HKU as an associate professor in Microbiology. Since 1991, he has been engaged in studies of SIV/HIV/AIDS pathogenesis and AIDS/SARS/COVID vaccines. In recent years, he has been focusing on the functional cure of HIV/AIDS (Hong Kong TRS project), COVID-19 vaccine and immunopathogenesis as well as cancer immunotherapy. He has published about 200 peer-reviewed SCI papers and is a Highly Cited Researcher ranked by Clarivate in the top 1%.
Name & Affiliation:
Prof Kelvin Kai-Wang To
The University of Hong Kong / Centre for Virology, Vaccinology and Therapeutics
Title: Protective immunity against SARS-CoV-2 variants among vulnerable populations
Abstract:
SARS-CoV-2 infection leads to significant morbidity and mortality, especially among older adults and patients with chronic medical illnesses. To mitigate the impact of SARS-CoV-2 infection among these vulnerable individuals, understanding the level of protective immunity is crucial. In this talk, I will share our findings on the humoral and cellular immunity against SARS-CoV-2 among various at-risk groups, including older adults, patients with chronic kidney disease, and patients with haematological disorders. I will also discuss how emerging SARS-CoV-2 variants affect the protective immunity in these populations.
Biography:
Prof Kelvin To is currently a Clinical Professor and Chairperson of the Department of Microbiology at LKS Faculty of Medicine, the University of Hong Kong. He holds a BSc (Microbiology) from the University of British Columbia, as well as MBBS and MD degrees from the University of Hong Kong. He completed his specialist training in clinical microbiology and infection. He is a fellow of the Royal College of Pathologists, Royal College of Physicians (Edinburgh) and the Infectious Diseases Society of America. He is a member of the Scientific Committee on Vaccine Preventable Diseases of Centre for Health Protection in Hong Kong.
As a clinician scientist, his research focuses on clinically relevant aspects of emerging respiratory virus infection, including pandemic and avian influenza viruses and emerging coronaviruses.
Name & Affiliation:
Dr Jasper Fuk-Woo Chan
The University of Hong Kong / Centre for Virology, Vaccinology and Therapeutics
Title: Novel virus- and host-directed COVID-19 therapies
Abstract:
Unlike severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV), SARS-CoV-2 has disseminated globally and continues to circulate in humans with emergence of new variants that may render existing vaccines less effective. Effective antivirals are essential for improving the clinical outcome of COVID-19 patients at risk of developing severe disease or complications. This talk focuses on the recent advances in the development of novel virus- and host-directed COVID-19 therapies. Specifically, the antiviral effects and mechanisms of the H84T-banana lectin and host enzyme inhibitors will be discussed.
Biography:
Dr Jasper Fuk-Woo Chan is Deputy Chairperson and tenured Clinical Associate Professor, Department of Microbiology, School of Clinical Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong. His research focuses on the diagnosis, treatment, and control of emerging infectious diseases with pandemic potential or special relevance to Asia. He has published more than 320 papers in these areas, including (co-)first/corresponding- authored articles in The Lancet, Science, and Nature. He has been ranked by Clarivate as a Highly Cited Researcher since 2021 and as a top 1% scholar by citations since 2015. He has served as expert member or ambassador of various international organizations, including as member of the WHO ad hoc Expert Group focused on COVID-19 disease modelling (WHOCOM) and as Young Ambassador of Science of the American Society for Microbiology. He and his team reported the world’s first familial cluster of COVID-19 that confirmed person-to-person transmission of SARS-CoV-2 – a finding which resulted in major policy changes for controlling the pandemic worldwide. His team also established the world’s first Syrian hamster model for COVID-19, which has now become one of the most commonly used animal models for COVID-19 research.
Name & Affiliation:
Dr Hin Chu
The University of Hong Kong / Centre for Virology, Vaccinology and Therapeutics
Title: The Role of Apoptosis in Coronavirus Pathogenesis
Abstract:
Highly pathogenic coronaviruses including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Middle East respiratory syndrome coronavirus (MERS-CoV), and SARS-CoV-1 vary in their transmissibility and pathogenicity. However, infection by all three viruses results in substantial apoptosis in cell culture and in patient tissues, suggesting a potential link between apoptosis and pathogenesis of coronaviruses. Here we show that a cysteine- aspartic protease of the apoptosis cascade, caspase-6, serves as an important host factor for efficient coronavirus replication. We demonstrate that caspase-6 cleaves coronavirus nucleocapsid (N) proteins, generating N fragments that serve as interferon (IFN) antagonists, thus facilitating virus replication. Inhibition of caspase-6 substantially attenuates lung pathology and body weight loss of SARS-CoV-2-infected golden Syrian hamsters and improves the survival of mouse-adapted MERS-CoV (MERS-CoVMA)-infected human DPP4 knock-in (hDPP4 KI) mice. Overall, our study reveals how coronaviruses exploit a component of the host apoptosis cascade to facilitate virus replication.
Biography:
Dr. Chu focuses on investigating the pathogenic mechanisms and host and viral determinants of emerging viral pathogens, with an emphasis on highly pathogenic coronaviruses. He has authored 146 publications with 59 of them as first/co-first or corresponding author (Google Scholar: h-index 48; Citation 27,970), including first and last corresponding authored publications in Nature. According to Clarivate Analytics' Essential Science Indicators, Dr. Chu is ranked as one of the world's top 1% scholars by citations and as a "Highly Cited Researcher" in 2021 and 2022. His research is supported by competitive grants including RGC-CRF, RGC-GRF, HMRF, NSFC, TRS, Health@InnoHK, and National Key R&D Program. As a recognition of Dr. Chu’s track record on coronaviruses, he was awarded the NSFC-Excellent Young Scientist Fund (Hong Kong and Macau) in 2021.
Name & Affiliation:
Dr Shuofeng Yuan
The University of Hong Kong / Centre for Virology, Vaccinology and Therapeutics
Title: PMI-controlled mannose metabolism and glycosylation determines tissue tolerance and virus fitness
Abstract:
Host survival depends on the elimination of virus and mitigation of tissue damage. Herein, we report the modulation of D-mannose flux rewires the virus-triggered immunometabolic response cascade and reduces tissue damage. Safe and inexpensive D-mannose can compete with glucose for the same transporter and hexokinase. Such competitions suppress glycolysis, reduce mitochondrial reactive-oxygen-species and succinate-mediated hypoxia-inducible factor-1α, and thus reduce virus-induced proinflammatory cytokine production. The combinatorial treatment by D-mannose and antiviral monotherapy exhibits in vivo synergy despite delayed antiviral treatment in mouse model of virus infections. Phosphomannose isomerase (PMI) activity determines the beneficial effect of D-mannose because simultaneous PMI depletion and mannose supplementation impair cell viability. PMI inhibition suppress a panel of virus replication via affecting host and viral surface protein glycosylation. However, D-mannose does not suppress PMI activity or virus fitness. Taken together, PMI-centered therapeutic strategy clears virus infection while D-mannose treatment reprograms glycolysis for control of collateral damage.
Biography:
Dr Shuofeng Yuan is currently an Assistant Professor in HKU Department of Microbiology. By focusing on small-molecule lead compounds that can be delivered orally and are cheaper and easier for patients to access, his efforts aim to help ensure the world is prepared to quickly develop and equitably deploy effective, accessible antiviral treatments when a pandemic threat emerges. By rewiring virus-induced lipidomic abnormity, he and colleagues discovered novel druggable factors such as sterol regulatory-element binding proteins (SREBPs) and Diglyceride acyltransferase (DGAT) for broad-spectrum antiviral therapy. Dr. Yuan has filed >10 patents with novel antivirals for emerging infectious diseases including influenza, zika and COVID-19. He is recognized as the worldwide “Highly Cited Researchers” 2021 and 2022 by Clarivate and published >40 first/co-first/corresponding-authored original research articles in the best journals including Nature and Science. Dr. Yuan recently received the Young Investigator Award by Pathogens Journal.
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