What a virus is and how it spreads
A virus is a genetic element wrapped in protein that depends on a host cell to replicate. What it is made of decides how it is classified, and it enters a host, replicates in its cells and leaves by many routes. Its error-prone replication lets it mutate, reinfect and adapt to new hosts, and most pandemics follow a jump from one species to another. The reproduction number measures how many people each infected person infects, and quarantine and isolation limit the spread.
What a virus is
A virus is a genetic element of RNA or DNA, wrapped in a protein shell and sometimes in a second shell, that can alternate between states inside and outside the cell. Strictly, viruses are obligate intracellular parasites: they depend entirely on the host cell for metabolism and replication. Because they have no metabolism of their own, they are not considered alive under traditional definitions of life. They are also called a quasi-species, partly for that reason and partly because they have no fossil record, which makes their phylogenetic trees difficult to construct.
How abundant viruses are and what else they do
Viruses are the most common biological entity on the planet, with an estimated 10³¹ of them; stacked on top of one another, they would reach 200 million light years into space. Every drop of water contains millions, and they are hardy enough to survive harsh conditions. Viruses are believed to have existed at least as long as cellular life and possibly before it, in which case they also influenced cellular evolution.
Viruses have been called bad news wrapped in protein. Not all of them are harmful, though: if they were, humans would not be here. Some protect against deadly bacterial infections, and weak viral infections prime the immune system. Their bad reputation comes from being heard of only when something goes wrong.
Beyond infection, viruses affect the food supply and the environment. Many of them infect bacteria, including bacteria that produce oxygen and carbon dioxide, and so they influence the balance of those gases and the temperature of the planet. Viruses are also model systems for many problems of basic biology: most of modern molecular biology, including DNA replication, was founded on studies of viruses, and oncogenes were first discovered in them. Because viruses are so good at infecting cells and transmitting genetic information, they can be used in medicine and biotechnology as vectors, for example as delivery systems, or to treat bacterial infections in phage therapy.
Size and genome
Viruses measure on average about 20 to 200 nanometres, but recently discovered large viruses such as mimivirus and the megaviruses can reach 500 nanometres. Genome size varies with them, from about 2,000 base pairs to 800,000 or even a million, which is more than some of the smallest bacteria carry. So does the number of genes, from two in the smallest viruses to up to a thousand in the largest.
The genetic material may be DNA or RNA, double- or single-stranded. A single-stranded RNA genome is positive or negative sense, marked with a plus or a minus beside the genome description. Positive-sense RNA can be translated directly by ribosomes, so it is functionally equivalent to mRNA. Some RNA viruses, such as retroviruses, have a DNA intermediate that they integrate into the host genome. A genome can also be circular, linear or segmented; the influenza virus, for example, has eight genome segments.
The virus particle and how it assembles
Every virus has a capsid that protects its genome, and a capsid with the genome inside is a nucleocapsid. Viral enzymes are added to it, and they differ by virus: polymerases, replicases, integrases and proteases among them. For some viruses that is the whole particle, while others also have a lipid envelope around the nucleocapsid, supported by a matrix. The proteins protruding from the envelope surface are the ones the immune system mostly recognises, and they are usually the ones that interact with the host cell and gain entry to it. Transmembrane proteins serve various functions in the viral life cycle. A single fully assembled, functional particle is sometimes called a virion.
The shape of the capsid drives the shape of the virus. A capsid may be helical or icosahedral, the 20-faced shape of a soccer ball, and everything that fits neither is grouped as complex.
A virus normally self-assembles, because all the information needed is encoded in its nucleic acid and proteins. The proteins and RNA of tobacco mosaic virus, the first virus discovered, self-assemble into a virion when they are simply mixed. Assembly is driven by hydrophobic and hydrophilic interactions between proteins rather than mainly by covalent bonds, because the particle must later come apart to release its genome. It is also driven by thermodynamics: the complete capsid is the most stable structure. A capsid built from many copies of two structural proteins, rather than from one giant protein, also saves genome space.
Classification and naming
Viruses are classified broadly as RNA or DNA viruses, then by the symmetry of the capsid, then by whether they have an envelope. The Baltimore class of a virus refers to the type of its genome.
Viruses are usually named after their physical characteristics. Coronaviruses are named for the crown they appear to wear under certain stains and at certain angles in microscopy, and togaviruses look as though they were wearing a toga. Picornaviruses are small, pico, RNA viruses. Hepadnaviruses are DNA viruses that affect the liver. Modern conventions also name viruses from genomic information.
Entry, replication and exit
Viruses enter the body by any route possible, including the whole gastrointestinal tract from mouth to anus. The epithelium, the thin layer of cells that covers all hollow organs, is easily permeable. The skin is tougher, so some viruses get through scratches or injuries, and others are carried by insects or other vectors whose bite delivers them into the blood.
Inside the body, every virus faces essentially the same set of tasks to establish an infection. It must first find the right cell, which often depends on whether it can interact with particular receptors on the cell surface, and then gain access to it, a step called activation. Taken in by endocytosis, the virus finds itself in a vesicle called the endosome. Under the right conditions, the genome is then released, replicated, transcribed and translated, in the cytoplasm or, depending on the virus, partly in the nucleus and nucleolus. Translation is the main battleground, because virus and cell compete for the same ribosomes: the cell does not want its ribosomes to translate viral messages, and the virus wants only its own messages translated. The particle then assembles and matures and buds off from the cell. It must reach the next cell while avoiding the immune system, and finally leave the organism to infect another one.
After replicating at the site of entry, a virus either remains localised or spreads. Rhinoviruses (rhino means nose) remain in the respiratory epithelium and produce cold symptoms. Some viruses spread to other tissues and to the blood, which is called viremia. Poliovirus, for example, is an enterovirus: it enters through the gut but spreads to neural tissue, where it can cause most of its damage.
Viruses also leave the host by any route possible. For cold viruses and coronaviruses, the primary route is respiratory secretions, aerosolised into tiny drops by sneezing or coughing, and a single drop can contain 100 million viruses. Fomites, everyday inanimate objects such as doorknobs or mobile phones, are another route: nasal secretions contaminate the object, the virus survives on it for a couple of hours, and the next person to touch it puts it into their mouth. Blood, urine, semen, milk and skin lesions, as with smallpox, are other routes.
Virulence
Virulence is the ability of a virus to cause disease, and it is a relative term: rabies and Ebola are highly virulent, while some viruses are virulent only under particular conditions, such as when the host's immune system is compromised. A virus needs a balance between virulence and propagation, because one that is too virulent kills its host before it can spread, and one that is not virulent enough is wiped out by the immune system.
Immunity, mutation and emerging viruses
Pandemics and epidemics usually involve acute infection. An acute infection is a rapid onset of symptoms that ends either in eradication of the virus or in the death of the host. Surviving one confers lifelong immunity to that specific virus. Some acute viruses cause illness again and again because they mutate at a high rate and evolve ways around the immune system, a property called structural plasticity: the virions of these viruses tolerate substitutions and remain infectious. Rhinoviruses and influenza viruses are highly plastic, which limits the ability to make effective vaccines against them and is why influenza vaccination is needed every year. Poliovirus is less plastic: a single vaccination can confer lifelong immunity, and vaccination has effectively eradicated polio. Infection can also be latent. Reinfection with the common-cold coronaviruses from one year to the next is thought to result mostly from their mutation rate.
In viruses with a high mutation rate, such as influenza, the rate comes from their polymerases, which are extremely error-prone. A viral RNA polymerase has an error rate of about one in 100,000, against about one in 100 billion for the human enzyme. In a typical RNA virus of 10,000 bases, about one in ten progeny genomes therefore carries a mutation. Where a billion virions are produced in a person each day, as with polio, about 100 million mutated progeny appear daily. Not all of these mutations benefit the virus or do anything, but about half of the bases in an RNA viral genome can be changed without killing the virus. For a genome of 10,000 bases, the number of possible sequences from simple mutations alone then approaches the number of atoms in the visible universe, and additional mechanisms that some viruses employ raise it further. Viral evolution is therefore inescapable and relentless.
This evolution produces emerging viruses: viruses in the process of adapting to a new host, and the host to them. They tend to be highly virulent at first because they meet an immune system with no experience of them. Over time, virus and host co-evolve and tend to converge on a less virulent virus and a more resistant population. Influenza viruses and coronaviruses are examples of constantly emerging viruses.
Types and strains
Strains are different geographical isolates of the same virus. When one type of a virus mutates into others, each with slightly different characteristics but functionally still the same virus, the resulting groups are types rather than strains. So the three groups of SARS-CoV-2 that an article on a study in PNAS called "strains" are better called types.
What a pandemic is and why pandemics recur
Whether a disease is labelled a pandemic depends not on how many people it kills but on how far it spreads. The ideal candidate spreads easily from person to person and also harms and kills those it infects. The word comes from the Greek pan, all, and demos, people. One definition of a pandemic is a new infectious agent that has spread to individuals on all continents except Antarctica.
Pandemics are as old as humanity because viruses are. Smallpox was described in ancient Egypt, and the pharaoh Ramses V had it. The Antonine Plague in the Roman Empire presumably came from Roman soldiers who brought measles or smallpox back from their travels to the Middle East. Pandemics were frequently seen as the wrath of the gods. Most pandemics occur after a species jump.
The spread of HIV can serve as a template for how other potential pandemics could arise. Viral sequencing traces HIV's evolution back to the late nineteenth or early twentieth century, when a hybrid simian immunodeficiency virus is presumed to have jumped from chimpanzees to humans through hunters who caught and butchered infected animals. The virus then remained unobserved and unrecognised in small isolated communities in Africa for 50 years before it became known, often following evolutionary dead ends. At some point an HIV isolate acquired what it needed to spread more easily, and urbanisation and global travel carried it into every corner of the world. On one account, humanity's evolution from small isolated hunter-gatherer communities into dense city populations that travel the globe has created the conditions for a viral "perfect storm". Whether other viruses, as yet undiscovered, are waiting to evolve the same way is an open question.
In 2012, several teams of self-styled virus hunters, among them Nathan Wolfe's, ran listening posts at hot spots around the world that monitored global "viral chatter", with the aim of stopping potential pandemics before they take hold and spread. One eventual hope is to recognise early unusual clusters of health complaints that might signal the beginning of an epidemic, an approach known as digital epidemiology.
One sociological account reads 2,000 years of infectious disease as a struggle for supremacy between microbes and humans, scored by fertility, mortality and population change through the phases of an epidemiological theory. It traces the move from hunter-gatherer to settled urban life and the shift of the mortality advantage from rural to city dwellers, a shift that has not always been straightforward or equally shared, and it names the microbes' four most frequently used advantages: human migration, trade, war and conquest. On this account the microbes, though on the Earth far longer than humans, have prevailed over them only for a few, if significant, decades at a time. The struggle may be not one for supremacy but a dance of mutual survival.
The basic reproduction number
The basic reproduction number, written R0, is the average number of people each infected person infects in a population with no pre-existing immunity. It depends on how the virus sheds and what kind of virus it is. At an R0 of one a disease spreads at a constant rate, and above one it spreads exponentially. R0 is about 1.5 for influenza, and measles is highly contagious. In May 2020, R0 for COVID-19 was about 2.5.
The COVID-19 figure was provisional, because the epidemic was not over. The R0 of SARS appears higher, yet SARS-CoV-2 is the more contagious of the two. The SARS figure reflects a finished epidemic with all the information in. The COVID-19 figure in May 2020 reflected an epidemic still under way, and it already included the effect of extensive social distancing.
Quarantine, isolation and contact tracing
In modern public health terms, quarantine separates people who may have been exposed to a contagious disease by restricting their movement over its incubation period. Isolation restricts the movement of people confirmed to have the disease. Contact tracing, done alongside both, identifies people who may have been exposed.
Quarantine predates microbiology: it was already used in early plagues, and it was already established that it helps. The word comes from fourteenth-century Venice, where during a pandemic sailors were not allowed to land for 40 days. Quarantine and isolation were used as early as the Black Death in the fourteenth century, and against cholera in the eighteenth century. Quarantine was considered paramount for controlling contagious disease and was frequently implemented with other public health measures, including isolation.
Reducing how much a population mixes lowers the projected peak number of people infected at one time. This is known as flattening the curve, and it is designed to keep health care systems from being overwhelmed. Quarantine and isolation also face challenges of compliance and sustainability. In 2020, concerns were expressed over the feasibility of prolonged, widespread quarantine and isolation, and the threat of a global recession linked to lost income, unemployment and disruption of trade, manufacturing and international travel. Extensive restrictive measures can also be a problem for people who earn low wages and have no paid sick leave or unemployment benefits. Concern was also expressed over a disproportionate rise in women's unemployment compared with men's in the United Kingdom and the United States.
Prolonged measures may prove difficult because of perceived infringements of individuals' constitutional rights. Their psychological impact must be considered carefully for groups such as the elderly, students and victims of domestic abuse, for whom effective support systems against anxiety and depression, and close monitoring, become imperative. The pandemic also raises the moral question of whether an individual's right to freedom of movement outweighs society's obligation to protect the elderly, and there may be no one-size-fits-all answer.