Cracking the mystery of flu transmission
Published: 28 Mar 2018
New and more effective flu medicines could be in the offing after researchers from NUS Medicine were able to discover how flu viruses infect people.
The finding was made by a multidisciplinary team led by Assistant Professor Thai Tran from the Department of Physiology, Professor Wang De Yun of the Department of Otolaryngology and Associate Professor Vincent Chow from the Department of Microbiology and Immunology. Using the protein called CD151, the team showed that flu viruses can hijack a unique class of proteins which are part of the body’s (host) respiratory cellular machinery. The viruses clone and multiply in the body before invading and colonising new victims while multiplying further in the bodies of infected individuals.
According to the World Health Organization, the flu affects approximately one billion people annually, three to five million of these severely and as many as 650,000 people die from the flu each year. Hence, this discovery is significant as it brings medical science a step closer towards the development of a potent vaccination and treatment regimen that can work against a broad spectrum of flu virus strains, and whose effectiveness and potency overwhelm viral resistance through all flu seasons.
Currently, because the flu virus changes its outer coat frequently, vaccine developments are based on predicting the key proteins on the outside of the flu virus in advance and blocking these proteins from binding to host cells. However, such strategies to find the “best match” for a particular flu season has obvious limitations as the virus may mutate frequently every few months. Alternative treatment strategies such as oseltamivir (Tamiflu) are only effective when prescribed early in the infection as they work by inhibiting replication of the virus, but the flu virus can become resistant if these agents are overused.
This is why the team used an approach which shifted the focus from the virus to the host, enabling them to home in on the host elements critical for the virus life cycle. Through this new approach, it was found that the virus hijacks a protein on the nucleus of host respiratory cells called CD151 and uses it to replicate. An essential step in virus replication is the production of new genetic material to form the core of new virus particles. In this case, the CD151 virus is used by the flu virus to export new genetic material out of the nucleus to form new viruses for further transmission and infection.
Using both human cells and preclinical models of the flu, the investigators showed that blocking CD151 slows down the formation of new flu viruses, allowing the host sufficient time to mount a strong immune response against the infection more effectively, simultaneously not provoking an overly exaggerated immune response, which could trigger complications such as asthma or respiratory failure.
“This newly discovered signalling pathway is conserved across H1N1 and H3N2 flu strains, which are the most prevalent circulating subtypes in humans, making this finding exciting as the development of CD151 blockers to stop the virus life cycle would negate the need for surveillance of circulating viruses each year,” explained Asst Prof Tran, the lead investigator of the study. The research was supported by grants from the Ministry of Education and the National Medical Research Council.
The finding also spells fresh hope for flu fighters like Professor Paul Tambyah, senior consultant from the Division of Infectious Diseases at the National University Hospital. “This is a very promising discovery as our current range of drugs available for the treatment of influenza is very limited. If this leads to a new class of drugs which can be used to treat influenza and its complications, it will be a great step forward in efforts to not only treat common (seasonal) flu but also prepare for a flu pandemic,” he said.
See Press Release.
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