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HKU reveals the secret in swine flu gene combinations which determines transmissibility of the virus in humans

09 Aug 2011

The H1N1 pandemic in 2009 (human swine flu) is the first influenza pandemic to emerge after scientists understood that pandemic influenza arises from animals. This is therefore the first opportunity to understand the mechanisms of pandemic emergence and to understand the viral genetic changes that allow an animal virus to acquire human-to-human transmissibility. Researchers at The University of Hong Kong Li Ka Shing Faculty of Medicine and overseas counterparts discovered that with the balanced activity of two specific virus surface proteins, haemagglutinin and neuraminidase determines the ability a swine influenza virus to transmit efficiently through the airborne route. The study opens the way to better understand the mechanisms of pandemic emergence, which will help scientists to better identify animal viruses of pandemic risk in the future.

The findings are published in the Proceedings of the National Academy of Sciences (PNAS), the official journal of the United States National Academy of Sciences.

About the study
This study builds on a comprehensive study of swine H1 viruses recently published by the same research team earlier this year in the prestigious journal - Nature.

Transmission of influenza viruses in ferrets mimics their transmission potential in humans and is the best animal model for studying virus transmission in humans. Swine H1 viruses representative of the major virus lineages found worldwide were tested for respiratory-droplet transmission from ferret-to-ferret. None of these viruses was efficiently transmissible in the ferret model, but one virus with North American Triple reassortant virus genes together with one gene segment (the M gene segment) acquired from a Eurasian avian-like swine virus was able to transmit very inefficiently from ferret to ferret.

Researchers then used influenza virus reverse genetics (a genetic engineering approach that allows manipulation of the influenza virus genome) to show that adding the neuraminidase gene segment from the pandemic virus to this swine virus allows the swine virus to transmit efficiently in ferrets by the airborne-route. This gene constellation recapitulates that seen in the pandemic H1N1 virus. Overall this work has demonstrated the need for a delicate balance of activity of the two virus surface proteins, the haemagglutinin and neuraminidase, in conferring the capacity for virus transmission in ferrets and humans.

About the HKU research team
The study was conducted by Dr. YEN Hui-ling, working together with Professor Malik PEIRIS, Professor GUAN Yi, Dr. Leo POON Lit-man, Dr. Michael CHAN Chi-wai at the Department of Microbiology, The University of Hong Kong Li Ka Shing Faculty of Medicine, and HKU-Pasteur Research Center, Hong Kong SAR, in collaboration with Professor Robert WEBSTER and Dr. Richard WEBBY at St Jude Children's Research Hospital, Memphis, USA, and Professor WONG Chi-huey and Dr. WU Chung-yi at Academia Sinica, Taiwan.

This work was funded by the Area of Excellence Scheme of the University Grants Committee (AoE/M-12/06), Hong Kong SAR, the Research Fund for Control of Infectious Disease of the Food and Health Bureau, Hong Kong SAR, and the Contract HHSN266200700005C from National Institute of Allergy and Infectious Disease, National Institutes of Health, USA.