What Is a Virus? A Particle That Runs on Borrowed Cells

The smallest viruses are twenty nanometres across, several thousand times narrower than a human hair and far below the reach of a light microscope, which is why they were not seen until the electron microscope of the 1930s, forty years after their existence had been inferred from filters that stopped bacteria but not infection. Every virus has a genome, which may be DNA or RNA, single- or double-stranded, and which in the smallest cases carries only three or four genes and in the largest over two thousand. Around it is a coat of protein, the capsid, assembled from repeating identical units into a helix or a twenty-sided solid, and many viruses wrap that in a membrane stolen from the last cell they left, studded with proteins that recognise the next.

That is all. There are no ribosomes to make protein, no mitochondria to make energy, no membrane pumps, none of the machinery of a cell. A virus carries the instructions and borrows everything else.

Infection starts with a fit. The proteins on the virus's surface bind to a specific molecule on the surface of a cell, which is why each virus infects only certain species and certain tissues: the influenza virus binds a sugar on cells lining the airway, HIV binds a receptor on a class of white blood cell, and the virus that causes COVID-19 binds a protein found on cells of the nose, lung and gut. The cell, mistaking the virus for something it needs, draws it in. The stages that follow:

• •Entry: the virus is taken into the cell or fuses with its membrane, and the coat comes apart to release the genome
• •Copying: the genome is read by the cell's own machinery, or by an enzyme the virus brought with it, to make viral proteins and thousands of new genomes
• •Assembly: the new proteins and genomes pack themselves into new particles, often without any help, because the coat proteins fit together only one way
• •Release: the particles leave by bursting the cell or by budding out through its membrane, and each is ready to bind the next

Viruses fail most tests for life. They have no metabolism, do not maintain themselves, and cannot reproduce without a host. They pass others: they carry genes, they evolve by natural selection, faster than anything else, and they are made of the same molecules as cells. Biologists mostly regard the question as a matter of definition rather than fact. A useful view is that a virus is alive inside a cell and inert outside it, in the way a seed is dormant until it meets soil; another is that viruses are not organisms but a kind of mobile gene, on a continuum with the jumping genes and plasmids that move within and between cells. What is not in doubt is that they are the most numerous biological entities on Earth, outnumbering cells about ten to one, with an estimated ten million trillion trillion of them in the oceans alone.

No fossil virus exists, so their origin is argued from genomes. Three ideas compete and may all be partly true. Some viruses look like escaped fragments of cellular genomes that acquired a coat. Some, particularly the giant viruses found since 2003, which have more genes than some bacteria, look like the remnants of cells that lost everything except the ability to hijack others. And some may descend from self-copying molecules older than cells, survivors from before the last common ancestor of all living things. Roughly eight percent of the human genome is made of the remains of viruses that inserted themselves into our ancestors' DNA, and one of them provides a protein without which the placenta cannot form. Viruses are not merely parasites on the tree of life; they have been carrying genes between its branches for as long as it has existed.

Because a virus uses the cell's own machinery, there is little to attack that does not also belong to the patient, which is why antiviral drugs are few and antibiotics do nothing. Those that exist target the handful of enzymes viruses bring with them, such as the one HIV uses to copy its RNA into DNA, or the proteins they use to enter and leave. The body's own defence is better: the immune system recognises viral proteins, makes antibodies to block them and kills infected cells, and a vaccine trains it in advance by showing it a harmless piece of the virus. Smallpox, which killed three hundred million people in the twentieth century, was eradicated by vaccination in 1980, and polio is close.

Once your immune system has beaten a virus, it usually remembers it, which is why most people catch measles or chickenpox only once. Other viruses dodge that memory. Influenza copies its RNA carelessly, so its surface proteins change a little every season, a process called antigenic drift, and last year's antibodies fit this year's virus less well. Occasionally two flu strains infect the same cell and swap whole gene segments, producing a virus the population has never met. That sudden change, antigenic shift, is how flu pandemics begin, and it is why the flu vaccine is reformulated every year.

The common cold works differently. It is caused by many viruses, and rhinoviruses alone come in well over a hundred types, so immunity to one gives little protection against the next. A third strategy is hiding. Herpes viruses, including the one behind chickenpox, retreat into nerve cells after the first illness and sit there quietly for years, out of reach of the immune system. The chickenpox virus can reawaken decades later as shingles, which is why an adult who had chickenpox as a child can still develop a painful rash from the very same infection.

Bacteria have viruses of their own, called bacteriophages or phages, from the Greek for bacteria eaters. They were discovered independently by Frederick Twort in Britain in 1915 and Felix d'Herelle in France in 1917, who noticed that something small enough to pass through bacteria-proof filters could wipe out a bacterial culture, leaving clear patches behind. Many phages have a striking shape: a geometric head packed with DNA, sitting on a tail with leg-like fibres. The fibres grip the surface of one particular kind of bacterium, and the tail punches through the cell wall and injects the DNA, leaving the empty coat outside.

Because each phage kills only certain strains of bacteria and leaves human cells alone, d'Herelle soon tried using them as medicine. Western doctors largely dropped the idea once antibiotics arrived in the 1940s, but phage therapy continued in the Soviet Union, especially in Georgia, and it is now being revived for infections that resist antibiotics. Phages also handed biology one of its most powerful tools. Bacteria defend themselves by storing snippets of phage DNA as a memory and cutting any matching DNA that gets in, and this system, called CRISPR, was adapted into the gene-editing method that won a Nobel Prize in 2020.

Viruses are usually described as far smaller than any cell, and most are, but in 2003 researchers described a virus so large that it had first been mistaken for a bacterium. Found inside amoebae, it was named Mimivirus, short for microbe-mimicking virus. Its particles are big enough to be seen with an ordinary light microscope, and its genetic material holds around a thousand genes, far more than a typical virus.

Since then many other giant viruses have been found, some even larger, in places ranging from seawater to ancient Siberian permafrost. They carry genes for tasks once thought to belong only to cells, which has reopened debates about where viruses came from and whether the boundary between viruses and living cells is as sharp as textbooks suggested.

A virus is a genome of DNA or RNA in a protein coat, sometimes wrapped in a stolen membrane, with none of the machinery of a cell. It reproduces by binding to a specific cell, injecting its genes and having the cell build copies, which is why it is inert outside a host and why so few drugs can touch it. Viruses evolve faster than anything alive, outnumber cells ten to one, have shaped the genomes of their hosts, and are best fought by the immune system, trained by vaccines.