Virusphere: What doesn’t kill you makes you stronger. Frank Ryan
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The ‘enteroviruses’ are also transmitted by the faecal-oral route and the viruses also replicate within the intestine, but curiously they do not present with the typical fever, vomiting and diarrhoea that typifies gastroenteritis. Instead they cause less predictable and often complex patterns of illness that affect various organs and tissues, for example, the brain and meninges, or the heart, skeletal muscles, skin and mucous membranes, the pancreas, and so on. The most familiar of this strange gamut of enterovirus-linked illnesses is poliomyelitis. All three ‘serotypes’ of the poliovirus, which have slight differences in their capsid proteins, are ‘enteroviruses’ within the family known as the picornaviruses. We might recall that these belong to the family of very small RNA-based viruses that includes the rhinoviruses. A cardinal feature of enteroviruses is that they are resistant to acid, so they can pass through the human stomach to replicate further down the alimentary tract. The poliovirus was the first of the enteroviruses to be discovered, earning its finders – Enders, Weller and Robbins – a Nobel Prize in 1954.
We should not be too surprised to discover that humans are the exclusive host of the poliovirus. The individual virion is a mere 18 to 30 nanometres in diameter. Under the electron microscope it has a capsid with the familiar icosahedral symmetry, which encloses a relatively simple RNA-based genome. In the small intestine, the virus binds to a specific receptor molecule in the lymphoid tissues of the pharynx and the ‘Peyer’s patches’ of the gut. Here the virus hacks its way into the interior of the cells, where it takes over the genetic processes to convert the cell into a factory for manufacturing daughter viruses. The daughter viruses are released through rupture of the infected cell, after which they re-invade neighbouring cells and repeat the process.
All of this sounds a trifle horrific and even potentially deadly. But in reality the great majority of individuals infected by poliovirus show little or no signs of disease other than, perhaps, a mild looseness of the bowels. But the stools of an infected individual will now be swarming with virus, which will be passed on to contacts through the faecal-oral route. Polio characteristically moves through populations in epidemic waves, with most of the infected unaware that they have encountered the virus. Only in a tiny minority does the virus make its way to the anterior horn nerve cells in the spinal cord, where infection and subsequent death of the nerve cells gives rise to the paralysis we saw in President Roosevelt. Bizarre as it might seem, the infection of the nerve cells appears to serve no purpose as far as virus transmission or evolutionary pathways are concerned. Indeed, this most dreaded complication of poliomyelitis appears to be coincidental.
The incubation period of poliovirus infection is usually a week to two weeks and, in the minority that show symptoms of infection, this involves a minor malaise, fever and a sore throat. These reflect the virus entering the bloodstream and will usually resolve without requiring any treatment and with no long-term consequences. Only in a small minority of those infected does polio give rise to a more severe illness. The onset is usually abrupt with headache, fever, vomiting – in some this may be accompanied by the neck stiffness typical of meningitis. Even still, the majority of symptomatic cases will go on to make a good recovery. But in the tiny but highly significant minority the paralysis of poliomyelitis sets in.
Paralytic poliomyelitis gets its name from the Greek polios for ‘grey’ and muelos, for marrow. This derives from the fact that the paralysis results from destruction of the grey marrow of the anterior horns of the spinal cord, which contain the cell bodies of the nerves that supply the muscles of arms, legs, chest and remainder of the trunk. The death of those cell bodies in the spinal cord causes a floppy style paralysis of the affected muscles, which is usually apparent within two or three days of the onset of the disease. In children affected by paralysis, this will have secondary long-term effects on limb growth and development. Bulbar poliomyelitis, a similar infection, causes damage to the nerve bodies of the cranial nerves, which results in paralysis of the pharynx and possibly accompanying difficulty with the muscles involved in breathing. This dreadful complication is why, before the advent of vaccination, some unfortunate patients ended up having to be supported by ‘iron lungs’.
We do not know why this unfortunate minority of infected individuals develop serious disease, including paralysis, from the poliovirus. There is some evidence that the virus gets into the central nervous system more commonly than is suggested by clinical signs. Indeed, as we shall see, this pattern of unwanted penetration into the central nervous system can feature in illnesses caused by other enteroviruses. One wonders if some genetic propensity might perhaps play some role, but it may be no more than bad luck. As we saw above, this pattern of paralysis in children, with its effects on limb growth, was recognised in the wall paintings of the tombs of pharaohs from Ancient Egypt. How puzzling then that such an ancient and easily recognisable disease was unfamiliar to European doctors until the latter years of the nineteenth century, when the first epidemics began in the cooler climates of industrialised Europe and the United States!
Such has been the dramatic success of vaccination programmes, using live attenuated viral vaccines taken by mouth, that polio has been largely eliminated from developed countries. In 2018, according to the Global Polio Eradication Initiative, the disease is now endemic in just three countries: Afghanistan, Nigeria and Pakistan. But, given the ease and extent of modern travel, we cannot rest assured until this historic and maiming disease is completely eradicated in these remaining pockets of potential contagion.
While poliomyelitis is now approaching global control, it is not the only enterovirus to afflict humanity. Other members of this virus family are still commonly encountered in developed countries, including viruses that can be baffling in their presentations and clinically unpredictable in the course of their illnesses. Perhaps the best known of these are the Coxsackie B viruses, which sometimes present with a condition known to doctors as epidemic pleurodynia. Also known as ‘Bornholm disease’, after the Danish island where it was first recognised, this can present as severe chest pain arising from inflammation in the intercostal muscles of the chest wall. Popularly known as ‘the devil’s grip’, the sudden onset and severity of the pain can mimic a heart attack. Coxsackie B viruses can occasionally cause inflammation of the brain, presenting as the condition known as myalgic encephalomyelitis, or ‘Royal Free disease’, named after the London teaching hospital where it first presented. The same enterovirus may also present with inflammation of the heart muscle, or myocarditis, coupled with inflammation of the membrane surrounding the heart, known as pericarditis, a combination that presents in both children and adults and can very occasionally prove fatal. Other enteroviruses, including the echoviruses and types 70 and 71 enteroviruses, can cause chest infections and various patterns of muscle, meningeal and brain infections, where the diagnosis of the causative virus may be exceedingly difficult to pin down.
Viruses and their associated illnesses can be very puzzling. Ever since we first discovered their enigmatic presence among us, questions have inevitably arisen as to the evolutionary purpose behind their behaviours. When faced with the unpleasant, sometimes life-threatening, effects of virus infections, we are inclined to wonder what possible benefit such behaviour might confer on the virus. In the case of the poliovirus we saw how it appears to be mere happenstance that the virus causes serious illness in a tiny minority of those it infects. But there are other viruses that sweep through the human population and inflict dreadful patterns of illnesses in the majority of those infected, sometimes accompanied by a high mortality. This is all the more baffling since all that matters to the virus is its survival and successful replication. Survival of the virus must surely be threatened by killing its host. When one views the same question from a medical perspective, we are inclined to question: why are some viruses so deadly?
The Four Horsemen of the Apocalypse feature in the biblical Book of Revelation, where, having been released by the opening of seven seals, they ride out on red, white, black and pale horses. Theologians differ in their interpretations of what these riders might signify, but one of the four is commonly interpreted as pestilence, which, in modern terminology, would be interpreted as plague. While the common childhood infections,