Malaysia and the region: A hotbed for emerging viral infections

By Professor Sunil K Lal

For the last 28 years, we have been studying virus-host relationships in various infectious disease models, including hepatitis E, SARS coronavirus and Influenza A virus. Our primary focus has been to understand virus evolution and viral pathogenesis during infection. We investigate how viruses result in severe disease conditions in an infected individual and how some individuals show higher resistance and incur mild disease against the same virus isolate.

The human innate immune response plays a significant role in this process, and a lot depends on the virus-host relationship. In other words, viruses are entirely dependent on host cells for their replication. The process of viral replication cannot happen without the help of the human it infects. In our research, we investigate cellular pathways and mechanisms that are exploited by the infecting virus to modulate the host machinery and resources towards the invading virus's replication.

Interestingly, viral strategies rest on carefully designed plans to keep the infected host cell alive, channel its resources and not trigger an alarm for the immune system to reach out with anti-viral defence. When all this is successful by viruses and their covert operation, the individual succumbs to the viral infection and shows signs of illness.
The extent and severity of the infection become a combination of many factors, primarily the ability of the virus to multiply efficiently in large numbers, during a minimum time and its ability to overcome the innate defence mechanisms that are part of every infected individual.

Every viral infection is a game and a balancing act between the host and the virus, with ultimately only one winner – the host or the virus. There are hundreds of viruses we breathe in and out every minute, but we seldom fall sick. This is because our body is fighting a constant battle with viruses and always winning. However, occasionally due to certain factors and conditions, sometimes our body loses out on this battle, and that's when we fall sick.

Also, viruses have evolved to become extremely complex yet remain compact. They are continually evolving, and they do this at a much faster pace than humans. This becomes a major challenge for researchers and drug-developers to try to develop an anti-viral or a vaccine against a rapidly changing target. All drugs against Influenza A virus currently available in the market focus on targeting one of the viral proteins; however, there is a rapid change brewing in this ideology.

Next-generation anti-virals are now focusing on targeting the host proteins that are not evolving as fast as the virus. The idea is to understand how the invading virus exploits host proteins and how the host proteins get modulated by the viral proteins to facilitate viral replication. This new strategy holds great promise for the future in combating changing viruses like Influenza and SARS.

Within South-East Asia, viral infections are rampant, and this region is considered the hotbed for new and emerging viruses. Recently there have been major outbreaks on Influenza A reported in many parts of Malaysia and an emerging SARS outbreak in Wuhan, China. In the past, there have been outbreaks of viral encephalitis, chikungunya, Hendra and Nipah, all emerging from this region. We find it intriguing to look at this region of the world and understand the underlying factors that make this region so vulnerable to emerging and re-emerging viral infections.

With over 150 high impact publications and three international books on the subject, we have narrowed it down to a collection of factors that make Malaysia and the region a hotbed for emerging viral infections.