How do viruses shape our world?

As frightening as they are as agents of disease, viruses can also do wonders — shaping and evolving from the very beginning of life. About 8 percent of our DNA comes from viruses that infected our long-ago ancestors and tinkered with viral genes into their genomes; Some of these genes now play crucial roles in the early stages of embryo development and in the placenta surrounding the 13-week-old foetus (pictured above). PHOTOGRAPH BY LENNART NILSSON, TT/SCIENCE PHOTO LIBRARY (COMPOSITE OF TWO IMAGES)

Let’s imagine an earth without viruses!

We wave our wands and they disappear:

The rabies virus suddenly disappeared, the polio virus, the dreaded and deadly Ebola virus, the measles virus, the mumps virus, and the various influenza viruses, and human suffering and death were greatly reduced.

HIV disappeared, and the AIDS disaster never happened again. Nipah, Hendra, Machubo and Sinobo are all gone — never mind the messy records they once left behind. Dengue fever disappeared; All rotavirus disappeared – a great pity for the hundreds of thousands of children who die each year in developing countries. The Zika virus disappeared; Yellow fever virus disappeared; Monkey herpesvirus B, which is carried by monkeys and usually fatal when transmitted to humans, was also gone; No one gets chickenpox, hepatitis, shingles, or even the common cold anymore.

Day flower? The virus was eradicated worldwide in 1977; Now, the last samples, stored in high-security cryogenic refrigerators, have gone ghostly. The SARS virus of 2003, which marked the alarm of the modern pandemic era, disappeared. And then, of course, there is the evil SARS-COV-2 virus, the one that caused COVID-19 and whose treacherous impact on society is so intractable, so dangerous and so easily transmitted that it no longer exists.

Do you feel better about everything?

Don’t!

The situation is more confusing than you might think. The truth is, we live in a world full of viruses — of infinite variety and quantity. In the observable universe, the oceans alone may contain more virions than stars. Mammals probably carry at least 320,000 different kinds of viruses. When you add in viruses that infect non-mammals, plants, terrestrial bacteria and every other possible host, the total reaches… Countless. Not only are they vast in number, but their impact is staggering: many of these viruses have brought adaptive benefits, not harm, to life on Earth, including human life.

Without them, mankind would not be able to continue. Without them, we would not have risen from the primal muck. For example, two different lengths of DNA derived from viruses are present in the genomes of humans and other primates. The surprising truth is that without them, pregnancy would be impossible. There is also viral DNA, which is present in the genes of land animals and, more surprisingly, helps to pack and store memories in tiny protein bubbles. There are other genes from viruses that help embryos grow, regulate the immune system, and suppress cancer — important effects that are only now beginning to be understood. It turns out that viruses played a key role in triggering major evolutionary shifts. If all viruses were eliminated, as we think they are, our planet’s rich biodiversity would collapse like a beautiful wooden house, with every nail suddenly removed.

Yes, a virus is a parasitic organism. But sometimes the parasite is more like symbiosis, in which the host and the host depend on each other and benefit from each other. Like fire, viruses are a phenomenon that is neither good nor bad. They can do good or harm — it all depends on the virus, it all depends on the situation, it all depends on your reference point. They are the dark angels of evolution, good and terrible. That’s what makes them so interesting.

To understand the diversity of viruses, you need to start with the basics of what they are and what they are not. It’s easier to say they’re “not something” — they’re not living cells. Depending on whether the cell happens to be a muscle cell or a xylem cell or a neuron, one cell at a time goes through massive assembly to form sophisticated machines for building proteins, packaging energy and performing other specialized functions in order to make up your or my body, an octopus or a primrose. Bacteria, also cells, have similar properties but are much simpler. Viruses don’t.

The question of what a virus is is so complex that its definition has changed over the past 120 years. Dutch botanist Martinus Beijerinck, who studied tobacco Mosaic virus, speculated in 1898 that it was an infectious liquid. For a while, a virus was defined largely by its size — something much smaller than a bacterium, but which, like a bacterium, causes disease. More recently, viruses were thought to be submicroscopic vectors with very small genomes that could replicate in living cells — but this was only a first step towards a more appropriate understanding. (See how the virus is seen up close.)

“I will defend the paradox,” the French microbiologist Andre Lwoff wrote in an influential 1957 paper, “The Concept of viruses,” that “viruses are viruses.” This is not a clear definition, but an objective caveat — in other words, “unique to themselves.” He cleared his throat and began his complicated explanation.

Lwoff knows that it is easier to describe a virus than to define it. Each virus particle is made up of a set of genetic instructions (written in DNA or other information-carrying molecules, RNA) wrapped in a protein capsule, known as a capsid. In some cases, the capsid is surrounded by a membranous envelope, such as the caramel on a caramel apple, that protects the virus and helps it grab onto cells. A virus can replicate itself only when it enters a cell and controls a “3D printing machine” that converts genetic information into proteins.

If the host cell is unlucky, it makes lots of new virus particles, and they cause the cell to rupture, and the cell becomes debris. Such damage — such as that caused by SARS-COV-2 in human airway epithelial cells — is part of how viruses become pathogens.

But if the host cell is lucky, the virus may simply settle into this cosy outpost for the time being — either dormant or reverse-integrating its small genome into the host’s — and bide its time. This possibility has implications for genome reengineering, for evolution, and even for our sense of identity as humans, which I’ll talk more about later. Here’s a hint: in a popular 1983 book, British biologist Peter Medaval and his editor wife Jane asserted that “no virus can do any good: a virus is, as we all know, ‘a piece of protein-wrapped bad news.'” They were wrong, as were many scientists at the time, and it’s understandable that anyone whose knowledge of viruses is limited to bad news like flu and COVID-19 still accepts this view. But today, some viruses are thought to be beneficial, wrapped in proteins for genetic scheduling, good or bad as the case may be.

Where did the first viruses come from? This requires us to look back about 4 billion years, when life on Earth emerged from a hodgepodge of long molecules, simpler organic compounds and energy.

Suppose some long molecule (probably RNA) starts replicating. As these molecules — the first genomes — reproduce, mutate and evolve, Darwinian natural selection will begin here. Seeking a competitive advantage, some molecules may have found or created self-protection within membranes and walls, giving rise to the first cells. These cells split into two by fission to produce offspring. They also divide in a broader sense, differentiating into bacteria and archaea, two of the three domains of cell life. A third, eukaryotes, appeared later. It includes ourselves and all other living things (animals, plants, fungi, certain microbes) that are made up of cells with complex internal anatomy. These are the three branches on the tree of life as we now describe it.

But where is the virus? Are they the fourth main branch? Or are they a mistletoe, a parasite that floats in from somewhere else? Most versions of the evolutionary tree ignore viruses entirely.

One view is that viruses should not be included in the tree of life because they are not alive. It’s a lingering debate, depending on how you define “live.” A more interesting idea is to take viruses into a big tent called life and explore how they got in.

There are three main hypotheses to explain the evolutionary origins of viruses, which scientists call virus primacy, virus escape, and virus reduction. The idea of virus primacy is that viruses predate cells, somehow assembled directly from a hodgepodge of primordial elements. The escape hypothesis postulates that a gene or piece of a genome leaks out of a cell, gets encamped in a protein capsid, and then starts “idling around” until it finds a new niche to start parasitising. The reduction hypothesis suggests that viruses originate in cells that become smaller under competitive pressure (easier to replicate if small and simple), shedding genes all the way down to a minimalist state where only the host cell can survive.

There is a fourth hypothesis, called the chimeric hypothesis, which is inspired by another class of genetic elements: transposons (sometimes called jumping genes). Their existence was derived by geneticist Barbara McClintock in 1948, a discovery that won her a Nobel Prize. These opportunistic elements achieve Darwinian success by jumping from one location in the genome to another, in rare cases from one cell to another, or even from one species to another, using cell resources to replicate themselves over and over again. Self-replication protects them from accidental extinction. They accumulate abnormally and make up about half of the human genome. According to this idea, the earliest viruses may have been created by these elements borrowing proteins from cells and wrapping their naked self in a protective capsid — a more sophisticated strategy.

Each hypothesis has its merits. But in 2003, new evidence of giant viruses pushed expert opinion in favor of the reduction hypothesis.

It is found in amoebas, single-celled eukaryotes. The amoebas were collected from water in a cooling tower in Bradford, England. Some of the amoebas have mysterious spots inside them that are large enough to be seen with a light microscope (viruses are generally so small that they can only be seen with an electron microscope), and they look like bacteria, but when scientists tried to examine the bacterial genes inside, they found nothing.

Finally, a team of researchers in Marseille, France, infected other amoebas with the stuff, sequenced and identified its genome, and named it Mimivirus because it mimics bacteria, at least in terms of size. It’s huge in diameter, bigger than even the smallest bacteria. Its genome is also large for a virus, at almost 1.2 million bases, compared with 13,000 for influenza and 194,000 for smallpox. (DNA, like RNA, is a long molecule made up of four different molecular bases, These bases are written with the first abbreviation instead. It’s an “impossible” virus: essentially a virus, but too big, like the four-foot wingspan of the newly discovered Amazon butterfly.

Jean-michel Claverie is a senior member of the Marseille research group. The discovery of Mimivirus “caused a lot of trouble,” he told me. Why is that? Because genome sequencing revealed four very unexpected genes — genes that encode enzymes that are thought to be unique cellular genes that have never been seen before in a virus. Claverie explains that these enzymes are among the components that assemble amino acids into proteins through translation of the genetic code.

As for the discovery of these “fancy” enzymes that are usually active in cells, Claverie said, “so the question is: what does a virus want when it has cells it can dominate?”

What on earth? The logical inference is that the Mimivirus keeps them as reservations because its lineage stems from the cell’s genomic reduction.

Mimivirus is not an accident. Similar giant viruses were soon found in the Sargasso Sea, and the early name became a genus. Mimivirus, which contains several giant viruses. Then the Marseille team found two more behemoths — again, amoeba parasites — one from shallow Marine sediment off the coast of Chile and the other from a pond in Australia. The two “parasites” are twice the size of mimiviruses and even more abnormal, and are assigned to a separate genus. As they explained in 2013, Claverie and his colleagues named it Pandora virus because “further research on them was expected to surprise.”

Claverie’s senior co-author on the paper is virologist and structural biologist Chantal Abergel (who is also his wife). “They’re challenging — they’re my baby,” Abergel told me with a tired smile about Pandora. It’s hard to tell what they are, she explains, these creatures are so different from cells, so different from classic viruses, carrying many genes that have never been seen before. “All of this makes them both fascinating and mysterious.” For a while, she called them NLFS (New Life-Forms) : New life forms. But based on the observation that “they weren’t replicating by fission,” she and her colleagues realized they were viruses — the largest and most puzzling viruses ever discovered.

These findings emboldened the Marseille team to propose a variant of the “reduction hypothesis.” Maybe the virus did originate from the shrinking of an ancient cell, something that no longer exists on earth. This “ancestral protocell” may differ from — and compete with — the universal common ancestor of all cells known today. Perhaps these protocells lost their competition and were shut out of all environments where life could be free. They may have survived as parasites on other cells and shrunk their genomes, becoming what we call viruses. In the realm of lost cells, only viruses may be left, like the giant rocks of Easter Island.

The discovery of giant viruses inspired other families

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