Viruses: More Friends Than Foes (Revised Edition). Karin Moelling
alone or has to survive outside of a host cell. Today, we detect only cell-dependent parasitic viruses. Evolution has not only proceeded from simple to complicated structures; it has also gone in the opposite direction. Complicated systems can become simpler: they can lose genes, delegate functions and become specialized. Depending on the environment, abilities can be acquired or given up and lost. Mitochondria are an example. Wait for the last chapter of the book!
How do viruses interact with their host cells? There are host cells without nuclei, the prokaryotes, comprising the bacteria and the archaea, and cells that contain nuclei, the eukaryotes, comprising insects, worms, plants, mammals, etc. These all harbor viruses, whereby the bacterial viruses have an extra name, bacteriophages or just phages. However, there is no need to differentiate between the viruses and the phages. They behave very similarly in their host cells. There are a few possible characteristics of their “life cycles” — or replication cycles: viral entry for infection, whereafter the virus can persist, integrate, replicate and/or lyse. Persistence — often unnoticed by the host — is a chronic or long-lasting state. Herpesviruses hide this way in neurons, where they can rest for years. Many plant viruses persist for ever, never acquiring a coat, never becoming active (or virulent), and always propagated together with the plant cell. Phages can persist as integrated prophages in cells; this is referred to as a lysogenic state. Also retroviruses and some other DNA viruses can integrate into the DNA of the host genome. The host then owns a few more genes. However, integration can also cause genotoxic or mutagenic effects and be harmful to the cell. Phages and viruses can lyse their host cell, setting free thousands of viral progeny, often as a response to stress, which is similar to our experience of stress: no space, no food! A dentist’s appointment can have the same effect, then herpeviruses crawl from their niche to the lips and cause a lesion.
Remember this general rule: foreign invaders can lead to integration or destruction linked by stress — this is true even for societies!
Will viruses destroy their hosts, and lead to the end of mankind by killing us all? No, that is a fairy tale and will not happen. It would be nonsense from the point of view of evolution, because then viruses would eliminate the basis for their own existence or “survival” and die out themselves. When most host cells have disappeared, then they are so scarce that the virus will never find the last ones. So if there is a shortage of hosts then viruses adjust to new types of hosts. This is the dangerous “zoonosis”, in which humans become infected by animal viruses that they have not encountered before. Before all hosts are eliminated, the viruses will find an arrangement. This is a transition from parasitic behavior to a co-existence — often mutualistic, that is, benefiting both the virus and the host. If the virus supports survival of the host then it increases the chances of surviving both for itself and for its progeny. Co-evolution can lead to less aggressive or less virulent behavior. That can happen in two ways: either the host develops greater resistance, or the virus becomes harmless. The latter can be achieved by endogenization of viral sequences into the host genome — our genome is full of them, a graveyard of former viruses. Endogenization will be discussed below.
Many viruses have become less harmful for their hosts during evolution. Ebola viruses, for example, have developed such an arrangement with bats (their principal host), and SARS viruses have done the same. Similarly, the equivalent of HIV in monkeys (SIV) does not cause diseases in monkeys any longer. So, if we wait long enough, shall we also have a friendly relationship with HIV? My prediction is yes, but we would have to wait for so long.
3 Viruses — how they make us ill
Viruses wrote history
One of the biggest success stories in medicine was the elimination of poxviruses. Poxvirus outbreaks should not be possible any longer, since humans have learnt how to vaccinate against the virus: cowpox prevents smallpox — that was the discovery of Edward Jenner, who first tested this vaccine with his son in 1796 and saved more lives than anybody else in the world has done. Jenner discovered the principle about how to generate a vaccine — use of a related virus causing a mild disease in humans, which protects against the dangerous virus. A cowpox instead of a smallpox virus is such an “attenuated” successful vaccine. The virus is considered extinct. Surprisingly there are occasionally still some pox outbreaks — viruses never disappear completely.
There are only a few laboratories left, in the USA and in Russia, where smallpox viruses are kept under safe conditions. How safe are they against abuse by a bioterrorist attack? This possibility seemed to become real after the anthrax bioterrorism in the USA in 2001, which caused some deaths and resulted in a hectic search for pox-vaccine leftovers, which had been stored for decades. They had been produced on animal skins and by no means corresponded to any acceptable safety standards, but they were then prepared as vaccine again after fivefold dilution to increase the number of doses! In my diagnostics department in Zurich we quickly developed a pox virus test. The necessary information about the viral sequence was freely available to everybody through the Internet! We even practiced how to react in the case of a pox virus alarm, how to prepare samples for a highly sensitive diagnostics method. The fear was a bioterrorist attack against the participants at the annual World Economic Forum at Davos. We dressed up in special safety coats including masks, which many people have seen in the movie “Outbreak” starring Dustin Hoffman. We practiced with a low pressure chamber, under the strictest safety conditions, which would prevent viruses from escaping to the outside — however, the chamber collapsed owing to someone opening the wrong valve by mistake, leaving us with a pile of wreckage. We were lucky, and never experienced an alarm. The fear was slowly forgotten worldwide!
Twenty years earlier I had witnessed the last pox alarm in Berlin. A patient was kept in a quarantine building with policemen sitting outside on high chairs to keep the exits in view and prevent the patient from escaping. Meanwhile, next door at the Robert Koch Institute, the only experienced technician who still knew how to test for poxviruses was busy opening chicken eggs to inoculate the virus and to incubate it for propagation — the only test available in those days. Pox alarm is shown in the movie “The Virus Empire — Silent Killers”. This very informative movie was produced by experts for teaching purposes, and I always showed it at the end of my virology teaching series at the University in Berlin; the series ended on Sundays — and was still attractive enough for the students to come. In the second part of the movie a fictive poxvirus alarm in Berlin is demonstrated.
Another virus, frightening us to this very day, is the influenza virus, the Spanish Flu, called H1N1. About one hundred years ago during World War I influenza viruses killed at least 20 million and possibly up to a hundred million people. The virus was only recently isolated — in 2005, from soldiers and an Inuit woman buried in the permafrost in the Alaskan tundra — and reactivated in the laboratory. The recovered virus was even able to infect animals. This was technically very demanding and in addition also extremely frightening. Rightly, the public media complained about it. Scientists wanted to know why this particular influenza virus was so deadly, especially for young men. There were only few special virus sequences which may have increased the virus’ affinity for lung cells and increased pathogenicity. (Other changes are in the polymerase or the nucleoprotein or the hemagglutinin, so there is still some controversy about which of the changes are deadly.) Major reasons for the pandemic were the war, hunger, humidity, cold temperatures, wounds, lack of hygiene, overcrowded shelters and field hospitals — all factors that cannot be deduced from the viral sequence, of course. All these factors contributed to the catastrophe. We also have to blame ourselves for it.
In 2009 the swine flu started in Mexico, caused also by influenza A H1N1 but distinct from the Spanish Flu. The World Health Organization (WHO) graded the outbreak as worldwide risk and declared it as an epidemic. This was due to a miscalculation. The ratio of people who died relative to the hypothetically infected people was wrong, because nobody knew the real infection rate in a country such as Mexico, where people do not go to see a doctor just with fever. The