Research News

28 Feb 2019

Neuraminidase activity and specificity of Influenza A virus are influenced by Hemagglutinin-receptor binding

Jimmy Lai, HKU-Pasteur Research Pole's laboratory manager, and Ho Him Wong, HKU-Pasteur Research Pole, published a paper in Emerging Microbes and Infections with Malik Peiris, Co-Director of the Pole and colleagues from the School of Public Health and Department of Pathology of HKU, and the Faculty of Veterinary Medicine and Animal Science, the University of Peradeniya, Sri Lanka entitled Neuraminidase activity and specificity of Influenza A virus are influenced by Hemagglutinin-receptor binding.


AbstractInfluenza virus hemagglutinin (HA) and neuraminidase (NA) are involved in the recognition and modulation of sialic acids on cell surface as the virus receptor. Although the balance between two proteins functions has been found to be crucial for viral fitness, interplay between the proteins has not been well established. Herein we present evidence for interplay between influenza HA and NA, which may affect the balance between two glycoprotein functions. NA enzymatic activities against sialoglycans were promoted by the presence of HA, which is in accordance with the level of co-existing HA. Such activity enhancement was lost when the HA-receptor binding properties were abolished by low-pH treatment, or by mutations at the HA receptor binding domain. Sialidase activities of NA-containing virus-like-particles and native influenza viruses were detected using different NA-assays and sialic acid substrates. Most pronounced HA-mediated NA enhancement was found when intact virions were confronted with multivalent surface-anchored substrates, which mimics the physiological conditions on cell membranes. Using recombinant viruses with altered HA bindings preference between α2,3- and α2,6- linked sialic acids, we also found that NA function against different substrates is correlated with the HA-receptor specificity. The effect of HA-receptor specificities on NA functions, together with the HA-mediated NA enhancement, may play a role in virus evasion of the mucus barrier, as well as in cross-species adaptation. Our data also indicates the importance of using multivalent substrates in future studies of NA functions. 

Recently, Jimmy also published a paper, Unravelling the Role of O-glycans in Influenza A Virus Infection, in Scientific Reports. This publication is the result of a long and fruitful collaboration between HKU-PRP and Institute for Glycomics in Queensland, Australia:

27 Feb 2019

HKU-Pasteur to be a partner in the Respiratory Diseases Research Center Project in the Greater Bay Area

On the occasion of the second Guangdong-Hong Kong-Macao Greater Bay Area Hygiene and Health Cooperation Conference held on February the 25th in Shenzhen, HKU-Pasteur Research Pole signed a cooperation project for a Respiratory Diseases Research Center with the State Key Laboratory of Respiratory Disease of the Guangzhou Medical University and the State Key Laboratory of Quality Research in Traditional Medicine of the Macau University of Science and Technology.

This project is the fruit of a very rewarding collaboration with the State Key Laboratory of Respiratory Disease of the Guangzhou Medical University and his Deputy Director, Professor Jincun Zhao, who has recently been appointed Honorary Professor with HKU-Pasteur and the School of Public Health of the University of Hong Kong.

Dr. Chris Mok, Research Assistant Professor at HKU-Pasteur, who spearheaded this collaboration years ago said: “The project will strengthen exchanges and cooperation in the prevention and treatment of respiratory diseases in the Guangdong - Hong Kong – Macao Greater Bay Area and boost innovative research strategies to understand and mitigate the impact, of respiratory diseases”.

The Respiratory Diseases Research Center will develop platforms for the prevention and control of respiratory diseases in the Greater Bay Area and the establishment of major cooperation projects, including training of research personnel.  Jincun Zhao added: “This collaboration will help establish a joint early warning, and emergency response to major respiratory infectious diseases in the Greater Bay Area to ensure the health of the population”.

The Guangdong-Hong Kong-Macao Greater Bay Area Hygiene and Health Cooperation ConferenceCo-organised by the Health Commission of Guangdong Province, the Food and Health Bureau, and the Health Bureau of the Macao Special Administrative Region Government, the Guangdong-Hong Kong-Macao Greater Bay Area Hygiene and Health Cooperation Conference aims at promoting experience exchange and sharing as well as strengthening co-operation among the three places on matters relating to hygiene and health in the Guangdong-Hong Kong-Macao Greater Bay Area.

08 Feb 2019

Breaking Bad: How Viruses Subvert the Cell Cycle

Ying Fan, former HKU-Pasteur PhD student under a Hong Kong PhD Fellowship from the Hong Kong Research Grants Council/HKU Foundation Postgraduate Fellowship, published with Roberto Bruzzone and Sumana Sanyal in Frontiers in Cellular and Infection Microbiology a paper entitled Breaking Bad: How Viruses Subvert the Cell Cycle.

Abstract: Interactions between the host and viruses during the course of their co-evolution have not only shaped cellular function and the immune system, but also the counter measures employed by viruses. Relatively small genomes and high replication rates allow viruses to accumulate mutations and continuously present the host with new challenges. It is therefore, no surprise that they either escape detection or modulate host physiology, often by redirecting normal cellular pathways to their own advantage. Viruses utilize a diverse array of strategies and molecular targets to subvert host cellular processes, while evading detection. These include cell-cycle regulation, major histocompatibility complex-restricted antigen presentation, intracellular protein transport, apoptosis, cytokine-mediated signaling, and humoral immune responses. Moreover, viruses routinely manipulate the host cell cycle to create a favorable environment for replication, largely by deregulating cell cycle checkpoints. This review focuses on our current understanding of the molecular aspects of cell cycle regulation that are often targeted by viruses. Further study of their interactions should provide fundamental insights into cell cycle regulation and improve our ability to exploit these viruses.

Keywords: viruses, cell cycle, checkpoint, infection, life cycle, host-pathogen interactions, phosphorylation, degradation
Ying Fan is now a postdoctoral fellow with an MRC fellowship in the MRC Protein Phosphorylation and Ubiquitylation UnitSchool of Life Sciences, University of Dundee, Dundee, United Kingdom, where she studies the role of the leucine-rich repeat kinase 2 (LRRK2) and in particular its kinase function in Parkinson's disease.​

08 Feb 2019

Unravelling the Role of O-glycans in Influenza A Virus Infection

Jimmy Lai, HKU-Pasteur Research Pole's laboratory manager, published a paper in Scientific Reports entitled Unravelling the Role of O-glycans in Influenza A Virus Infection with fellow colleagues from the Institute for Glycomics in Queensland, Australia. This publication is the fruit of a long and rewarding collaboration between HKU-PRP and the australian institute.  

AbstractThe initial stage of host cell infection by influenza A viruses (IAV) is mediated through interaction of the viral haemagglutinin (HA) with cell surface glycans. The binding requirement of IAVs for Galβ(1,4)Glc/ GlcNAc (lactose/lactosamine) glycans with a terminal α(2,6)-linked (human receptors) or α(2,3)-linked (avian receptors) N-acetylneuraminic residue commonly found on N-glycans, is well-established. However the role and significance of sialylated Galβ(1,3)GalNAc (core 1) epitopes that are typical O-glycoforms in influenza virus pathogenesis remains poorly detailed. Here we report a multidisciplinary study using NMR spectroscopy, virus neutralization assays and molecular modelling, into the potential for IAV to engage sialyl-Galβ(1,3)GalNAc O-glycoforms for cell attachment. H5 containing virus like particles (VLPs) derived from an H5N1 avian IAV strain show a significant involvement of the O-glycan-specific GalNAc residue, coordinated by a EQTKLY motif conserved in highly pathogenic avian influenza (HPAI) strains. Notably, human pandemic H1N1 influenza viruses shift the preference from ‘human-like’ α(2,6)-linkages in sialylated Galβ(1,4)Glc/GlcNAc fragments to ‘avian-like’ α(2,3)-linkages in sialylated Galβ(1,3)GalNAc without involvement of the GalNAc residue. Overall, our study suggests that sialylated Galβ(1,3)GalNAc as O-glycan core 1 glycoforms are involved in the influenza A virus life cycle and play a particularly crucial role during infection of HPAI strains.