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05 Jul 2018

HKU-Pasteur Research Pole advances the understanding of viral infection mechanism on dengue fever and related flavivirus diseases

Professor Sumana Sanyal, team leader, Tami Zhang and Iolanthe Lan published a paper advancing the understanding of viral infection mechanism of dengue fever and related flavivirus diseases, providing a solid foundation to further the development of effective therapeutic interventions against flavivirus infections. The findings are now published in Cell Host & Microbe, a leading peer-reviewed scientific journal.

Dengue virus is the most prevalent mosquito-borne viral pathogen and has become a global threat in recent decades, causing an estimated 100 million infections worldwide every year. Currently, there is no antiviral against dengue available and the efficacy of corresponding vaccine is yet to be assessed. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. 
 
Understanding the host cellular pathways that are exploited in the course of infection can provide insights into the development of antivirals and vaccine against dengue. A small tag-like regulatory protein, namely ubiquitin, can be added on or removed from other proteins via a mechanism called ubiquitin modification. Ubiquitin modification system has been reported to be involved in a diverse array of infectious diseases including dengue, yet a precise understanding of how ubiquitin modifications regulate either the host or viral components remains unknown. This study aims to address this question.

 

 

04 Jul 2018

The Hurdles From Bench to Bedside in the Realization and Implementation of a Universal Influenza Vaccine

Sophie Valkenburg, principal investigator at HKU-Pasteur, and team members Maireid Bull and Athena P.Y. Li  just published, with Nancy H.L. Leung, Li-meng Yan, Leo L. M. Poon and Benjamin Cowling (WHO Collaborating Centre for Infectious Disease Epidemiology and Control, School of Public Health, The University of Hong Kong) the review The Hurdles From Bench to Bedside in the Realization and Implementation of a Universal Influenza Vaccine in Frontiers in Immunology.
 
“Influenza viruses circulate worldwide causing annual epidemics that have a substantial impact on public health. This is despite vaccines being in use for over 70 years and currently being administered to around 500 million people each year. Improvements in vaccine design are needed to increase the strength, breadth, and duration of immunity against diverse strains that circulate during regular epidemics, occasional pandemics, and from animal reservoirs. Universal vaccine strategies that target more conserved regions of the virus, such as the hemagglutinin (HA)-stalk, or recruit other cellular responses, such as T cells and NK cells, have the potential to provide broader immunity. Many pre-pandemic vaccines in clinical development do not utilize new vaccine platforms but use “tried and true” recombinant HA protein or inactivated virus strategies despite substantial leaps in fundamental research on universal vaccines. Significant hurdles exist for universal vaccine development from bench to bedside, so that promising preclinical data is not yet translating to human clinical trials. Few studies have assessed immune correlates derived from asymptomatic influenza virus infections, due to the scale of a study required to identity these cases. The realization and implementation of a universal influenza vaccine requires identification and standardization of set points of protective immune correlates, and consideration of dosage schedule to maximize vaccine uptake.“
 

See the review online.

27 Jun 2018

Advancements in host-based interventions for influenza treatment

Dr Suki Lee, principal investigator at HKU-Pasteur Research Pole, and her team have recently published a review paper in Frontiers in Immunology to discuss the latest advancements in novel host-based approaches with potential for influenza treatment.
 
Viruses rely on host cellular functions to replicate, recent therapeutic developments focus on targeting host factors involved in virus replication. Besides controlling virus replication, virus-induced host immune response, such as the latest ideas suggesting the involvement of innate lymphoid cells and NADPH oxidases in influenza virus pathogenesis as well as the renewed interest in immune cell metabolism may serve as potential targets for drug development.
 
 

07 Jun 2018

Whole transcriptome analysis reveals differential gene expression profile reflecting macrophage polarization in response to influenza A H5N1 virus infection

Dr Suki Lee, principal investigator at HKU-Pasteur Research Pole, and her collaborators at University of Toronto and The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Canada and University of Notre Dame, Indiana, USA have recently published a work in BMC Medical Genomics and described the earliest molecular events in influenza virus infected human macrophages using RNA-Seq. 
 
Their data revealed that the two macrophage populations named M1 (classically activated) and M2 (alternatively activated) macrophage subtypes respond distinctly to influenza A virus infection, while the dysregulated gene expression in response to the infection by highly pathogenic avian H5N1 virus occurs specifically in M1 subtype.
 
This study provides important mechanistic insights into the understanding of influenza viral pathogenesis and the multi-faceted host immune responses elicited by H5N1 virus infection and suggests potential candidates as therapeutic targets for treating influenza disease.
 

Learn more.

06 Jun 2018

Joao Pombo and Sumana Sanyal published a review on Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections

Joao Palma Pombo, HKU-Pasteur, and Prof Sumana Sanyal, team leader at HKU-Pasteur, published a review on Perturbation of Intracellular Cholesterol and Fatty Acid Homeostasis During Flavivirus Infections in Frontiers in Immunology. 

This review summarises the recent advances that have been made to understand how lipid metabolism in human cells is altered upon infection by viruses from the Flaviviridae family. This family includes dangerous pathogens such as Dengue virus, Zika virus, Hepatitis C virus, and West Nile virus, which share similar steps of a life cycle that heavily relies on the cellular secretory pathway and production of intracellular membranes.

These metabolic changes can be caused by the viruses themselves, as a survival strategy, given that enhanced cholesterol or fatty acid production generates a greater pool of energy resources and building blocks for enhanced membrane production, both of which support the viral life cycle. However, metabolic alterations can also be induced by the host cell itself in response to infection, since specific alterations in lipid metabolism can trigger an innate immune response against viruses.

The review is available online.

04 May 2018

Recognition of double-stranded RNA and regulation of interferon pathway by toll-like receptor 10

Suki Lee, principal investigator at HKU-Pasteur Research Pole, and her colleagues at HKU School of Biomedical Sciences and Chinese Academy of Sciences have recently revealed a novel nucleotide sensing receptor and provides new mechanistic insight explaining its role in regulating IFN response in an article for Frontiers in Immunology.

Toll-like receptor (TLR)-10 is the least characterized TLR and still remains an orphan receptor, with only very limited information available regarding its localization, agonist, signaling and function. We have revealed lately that TLR10 is predominantly localized to endosomes and binds dsRNA. We provided different lines of evidences to demonstrate that dsRNA is in fact a ligand for TLR10 sensing and signaling, thereby identifying a previously unrecognized role of TLR10 as a novel nucleotide sensing receptor. We also revealed that TLR10 competes with TLR3 for ligand binding and proposed a model to illustrate the mechanisms for dual functions of TLR10 in the regulation of dsRNA-mediated IFN signaling. This work provides new mechanistic insight explaining the major role of TLR10 in regulating IFN response upon dsRNA stimulation.

As there is increasing evidence suggesting the involvement of TLR10 in different disease pathogenesis. We believe that these new findings not only provide important fundamental insights to the understanding of immunobiology of TLR10, but also bring indispensable importance to further investigate the role and functional relevance of TLR10 in diseases. Modulation of TLR10 signaling may thus provide a unique option to fine-tune fundamental physiological pathways involved in disease pathological conditions.

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