Читать книгу Viruses: More Friends Than Foes (Revised Edition) - Karin Moelling - Страница 33

Viruses are not lifeless — at least not as lifeless as a stone or a crystal. One can over-simplify the issue and say that anything smaller than a virus is lifeless, and what is larger is alive. So viruses are at the borderline: dead or alive or both. I do not see a singularity, no point, no sharp borderline, but rather a continuous transition from individual biomolecules all the way up to the cell. At the origin of life RNA viruses were around as the largest biomolecules, and from then on they have always been present.

“What is life?” This question was asked in 1944, in the title of the famous book by the physicist Erwin Schrödinger, a thesis that mobilized a whole generation of physicists into doing biological research. Life follows the laws of thermodynamics and energy conservation. Living cells are characterized by negative entropy based on organized structures, whereby entropy is often simply described as a “measure of disorder”. For example, left to itself my desk becomes more and more untidy; however, if I can muster enough energy to clear up, then it becomes ordered and tidy. Life and the second law of thermodynamics follow this rule: nutrition and energy allow an orderly life. Admittedly, Schrödinger was asking about the laws of life, not the origin of life.

I think that NASA must have a good definition of life, because NASA is trying to find life outside our planet. They surely know what they are looking for. Jerry Joyce, then at the Salk Institute in California, may have contributed to their definition when he succeeded in producing self-replicating RNA in a test-tube, RNA that was also capable of mutating and evolving. This was his approach to “repeating the origin of life”. He may have inspired the US space agency NASA, which formulated a definition of life as a self-replicating system containing genetic information and able to evolve. (I would even omit the word “genetic”, because structural information able to evolve would also be possible. I am thinking of viroids.)

Viruses can be compared to apples. An apple on a table cannot duplicate itself and turn into two apples — and a virus cannot do that either. An apple needs earth to become an apple tree and thereby to produce new apples. Are apples alive? What then of viruses? Can Charles Darwin help? He pictured a “warm little pond” as the place where life possibly originated, and imagined that the beginning was simple — but he predicted no more than that. A virus needs a pond, or at least a test-tube — an environment with nutrients for replication and for the production of progeny. And viruses are simple. So viruses are more alive than stones and only stones are really dead. Surprisingly, some viruses can aggregate and form symmetrical quasi-crystalline structures, which are extremely stable and heat-resistant, and in that respect they do indeed resemble stones. Crystals with malformations can even perpetuate their misfolding in a manner that looks almost like replication. Some protein aggregates in the brain can behave like this — prions for example; so are they then also something like viruses? I suggest that, as we shall see!

Bacteria are generally accepted as living microorganisms: they can divide and thus replicate themselves, and — most importantly — they can synthesize proteins. Protein synthesis is accepted as an important borderline marker distinguishing living from non-living matter. Bacteria also need food from the outside; yet they are not completely independent entities either. And bacteria are not simple! There is no such thing as a biological “perpetual-motion machine”, something that can get away without an energy supply. Yet energy does not necessarily have to come from a cell. Energy can be chemical energy, without any sunshine around, as in the case of the black smokers in the depths of the ocean.

Most surprisingly, the recently discovered giant viruses contain components for protein synthesis. So they are very close to the living bacteria, they are “quasi-bacteria”. Accordingly, the giant viruses are also called “mimiviruses”, because they seem to mimic bacteria. Just like bacteria, these giant viruses are hosts for smaller viruses, which replicate inside the bigger ones. All this was extremely irritating for classical virologists, because no previous convention or definition of viruses fitted for these giant viruses. Their discovery in 2013 was commented upon in the journal Nature to the effect that viruses now qualify to take a seat at the table where life is being debated, and that they should be placed at the bottom of the tree of life, this is what the discoverers of mimiviruses hoped! At the bottom there were no cells yet, and there are no mimiviruses — both are huge in comparison with viruses, therefore both cannot represent the origin of the tree of life. Probably, the early viruses did not need cells. This is a risky idea, and the only complication in my speculation that “viruses came first”. Today’s viruses need cells, but that could have been the result of long evolution. Indeed, there are the viroids, naked RNAs, which can replicate and evolve and may initially not have depended on cells as they do today. They are able to do all this in Joyce’s test-tube — no cell. They could be termed “naked viruses”.

Viruses are inventors and suppliers of genetic innovation. They built up our genomes. This is what I believe, and I shall mention it more than once, my credo, my ceterum censeo.

Viruses have certainly contributed to building cells. This is indeed a hard fact and no speculation. Today they are parasites and depend on cells. A parasite can delegate functions to its host and get away with fewer genes than if it is 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.