Feeling lost, depressed and lonely while jobless? Email gilbert@transitioning.org if you need to access our free volunteer career coaching or counselling services. Don't suffer alone, seek help! Thanks for visiting!
Story
Understanding the ‘mind’ of a virus
By Paul Ananth Tambyah
Anthropomorphising is the process of making something that is not human behave like a human. We do that all the time. We describe our cars as being temperamental, our pets as being kind or loyal and our computer keyboards often as having minds of their own.
The reason we do this is that it helps us to understand them better and even relate to them with greater sensitivity.
There is a slogan that has been going around some circles in Singapore with regard to the current swine origin H1N1 2009 influenza A pandemic: Know The Enemy. It is very important to have a good understanding of what the virus is, what it does, where it lives and what it is likely to do. I do apologise for anthropomorphising, but I hope it helps us understand the virus better.
To understand the influenza A virus, it is critical to understand what viruses are in the first place. Unlike bacteria which can live on their own for prolonged periods of time in very hostile environments, viruses are what scientists describe as obligate intracellular parasites. Viruses are intracellular – this means that they live inside the cells of the human body or whichever animal or plant that they infect.
They cannot survive for long in the environment as they lack the basic structures for independent living that would protect them from the sunlight or chemicals in the air. They obtain everything they need – food, all the building blocks for their structures and even the means for reproducing themselves – from the host animal or plant that they infect.
As a result, viruses have very simple structures. They are basically chains of DNA or RNA (the genetic material common to all living things) surrounded by proteins. The genes they have tend to be very basic – just enough to allow them to ‘borrow’ genetic material from their host to reproduce and for some basic functions like getting into host cells and obtaining the nutrients that they need.
A virus usually has only one set of ‘keys’ to allow it to enter whichever host cell it is best suited to live in. The result of this is that viruses tend to be very specific. In other words, a virus that attacks tobacco leaves is highly unlikely to have the genes to allow it to enter human cells or to make use of human DNA and proteins.
Viruses are parasites. This is a term that many of us are familiar with as we have all had friends from schooldays who keep borrowing things but never return them! This means that viruses obtain everything that they need from the host and do not contribute anything in return. While that seems pretty unfair, it is important to remember that it is not in the interests of a virus to kill the host. Once the host is dead, the food supply disappears. Your friend who keeps borrowing your pencils and notes knows that at some point, he has to stop asking or you will no longer ‘friend’ him.
Through millions of years of evolution, successful viruses have ‘realised’ that they should not kill off the host. They should keep the host alive for as long as possible so that they can keep ’sucking’ the nutrients out of the host and reproduce and spread widely.
To take a real-life example, the Ebola virus is actually a very unsuccessful virus as it enters the human from an unknown source and rapidly starts destroying the host cells. Within days, the host is often dead and the virus has no chance to spread widely as it dies with the host. There have been dozens of Ebola outbreaks in the last few years, with most of them confined to small rural areas.
On the other hand, the HIV virus is probably one of the world’s most successful viruses. It infects someone, then engages in a long drawn-out battle with the host immune system over a period of 10 years. During that time, the host has no symptoms and can go about having unprotected sex, sharing needles, et cetera, without knowing, thus allowing the virus to spread widely before the host gets any symptoms or signs at all.
Many of these successful viruses are RNA viruses. RNA, unlike DNA, has only one half of the famous double helix. There are fewer ‘quality control’ processes and thus many more mutations that occur when an RNA virus makes a copy of itself. When we get a cut, our skin cells make near perfect copies of themselves through the process of DNA replication, which has ‘editing software’ in place to make sure that there are no mistakes.
When an RNA virus such as influenza or HIV or hepatitis C tries to make a copy of itself, it will make a mistake roughly 1 per cent of the time. Given that viruses reproduce several times a day or hour depending on the environment, that is a very high error rate. Most of these errors are harmful to the virus and the mutated virus dies out, leaving the ‘regular’ virus to continue living in the host.
On the other hand, some of these mutations enable the virus to make better use of the host proteins, move from one host cell to another or avoid the host immune system. These rare mutations then persist and the viruses with those mutations take over the whole population of viruses through the process of natural selection described so elegantly by Charles Darwin more than a century ago. The same principle Darwin described in the birds in the Galapagos islands applies to viruses in the noses of people, for example.
If a mutation occurs that allows a virus to better survive in the ecological niche that is our nostrils, then it will persist and that strain of virus will dominate the others in the ’survival of the fittest’. The rest of the viruses in the said nostrils will be rapidly eliminated by the host immune system, which does not like foreign invaders.
Antiviral drugs also change the environment, making it more hostile to viruses by various mechanisms. Viruses that have mutations that allow them to overcome antiviral drugs such as Tamiflu (oseltamivir) will thrive if the environment is full of these drugs used indiscriminately. If the drugs are used in limited and appropriate ways, there is little survival advantage for the virus to mutate to avoid the drugs, although this might occur by chance.
The main goal of a virus is to survive and multiply. If a mutation helps a virus to survive and have an edge over the other viruses in the area (nostrils, et cetera), it will persist in future generations of that strain of virus, which will then become the most successful virus around.
Mutations that help a virus kill the host are generally not helpful. Who wants to kill the goose that is laying the golden eggs? Obviously, a virus with merely a dozen or more genes is not capable of thinking like an evolutionary biologist. Thus, many mutations have effects which can be unpredictable and can possibly be detrimental to itself.
In other words, the virus can accidentally become more lethal because of some transient survival advantage, but the vast majority of viruses throughout history have tended to move into less virulent forms. That ensures that they have a better relationship with the host, surviving for a long time in the majority of them by avoiding the host immune system and only occasionally killing off a few by mistake.
This is perhaps best illustrated by the enterovirus 71, which causes the hand, foot and mouth disease. Studies done in Taiwan by Dr Monto Ho and colleagues showed that when they had big outbreaks of HFMD, more than a million children were asymptomatically infected by a virus that had become well adapted to humans. Several hundred were sick, and there were unfortunately a number of deaths. In other words, the virus ‘wanted’ to spread rapidly among the children of Taiwan but ‘accidentally’ killed a few of them as tragic collateral damage of its proliferation strategy.
The other feature of successful viruses is the ability to avoid the host immune system. Influenza does that annually by mutating to new forms every year. That is why the flu vaccine has to be given every year. The good news about the Influenza A H1N1 2009 is that it appears to be related to a virus circulating from 1918 to 1957, thus people born before 1957 appear to be relatively protected from infection as they have immunity to the current virus. The few who do get infected however, as with regular seasonal flu, are at higher risk of complications because of their age and underlying medical conditions. Again, in Singapore, the vast majority of cases were under 30 years of age, suggesting that the same is true here.
I do not have a crystal ball, but I would think that the influenza A H1N1 2009 virus, which has now become well adapted to humans and is able to spread like wildfire despite the best efforts of governments worldwide to contain it, is unlikely to turn lethal. After all, if in the space of two months, you have managed to expand your business from some small farms in Mexico to 90 countries all over the world including the major financial markets, even the toughest markets to enter such as Hong Kong and Singapore, why would you try to change your business plan?
Dr Margaret Chan, the director- general of the World Health Organisation (WHO), put it very well when she said ‘the virus is not stoppable’ and ‘further spread is inevitable’. This is not due to some kind of failure of the WHO or any governmental system. It is simply the result of a fast evolving virus.
Influenza has been like that for centuries, spreading rapidly once it acquires the ability to spread from person to person. It is much more contagious than Sars or even chicken pox, for example. The public health goal then is to identify the individuals who are at highest risk of complications and to protect them. That is what mitigation is all about. As Dr Chan pointed out: ‘The WHO continues to recommend no restrictions on travel.’ Surveillance is the key, as she pointed out.
In Singapore, the Ministry of Health has a sophisticated multi- level surveillance system in place that will track all aspects of the disease from severe pneumonia cases to children admitted to hospital, to polyclinic attendees for coughs and colds. Even in the worst-case scenario, 30 per cent to 40 per cent of the population will have symptomatic infection, that is, a cough or cold. Around 0.2 per cent to 0.4 per cent of those who are infected will become severely ill – mainly those with underlying illnesses such as diabetes or heart or lung disease.
With good medical care, and by focusing our resources on the sick instead of the well, we can significantly reduce the death rate from influenza A. There is no point in trying to become part of the 30 per cent that will get a cough or cold by deliberately trying to get infected with this ‘mild’ virus just because of some theoretical risk of the virus acquiring a lethal mutation by mistake. The data from the Tan Tock Seng researchers is very reassuring. Twenty per cent of the first 50 Singaporeans infected with H1N1 had such a mild illness that they did not even have a significant fever. Again, that is the hallmark of a successful virus – work your way quietly into the system so you can spread rapidly and globally.
In summary, if you want to be a successful virus, you should be well adapted to the host’s nose and upper airway, be able to avoid the host immune system, try to avoid antiviral drugs if they are used too widely, and don’t try doing something silly like killing off your food supply!
The writer is Associate Professor, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore. He is also Head, Division of Infectious Diseases, University Medicine Cluster, National University Hospital, National University Health System.
How a virus succeeds
A feature of successful viruses is the ability to avoid the host immune system. Influenza does that annually by mutating to new forms every year. That is why the flu vaccine has to be given every year.
Related posts:
