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The Uncommon Cold: Rhinovirus
Around 3,500 years ago, an Egyptian scholar sat down and wrote the oldest known medical text. Among the diseases he described in the so-called Ebers Papyrus was something called resh. Even with that strange sounding name, its symptoms—a cough and a flowing of mucus from the nose—are immediately familiar to us all. Resh is the common cold.
rhinovirus itself is relatively mild. Most colds are over in a week, and 40 percent of people who test positive for rhinoviruses suffer no symptoms at all.
Human rhinoviruses may help train our immune systems not to overreact to minor triggers, instead directing their assaults to real threats.
Looking Down from the Stars: Influenza Virus
Amidst all the mysteries of the flu, the origin of the virus is clear. It came from birds. Birds carry all known strains of human influenza viruses, along with a vast diversity of other flu viruses that don’t infect humans. Many birds carry the flu without getting sick. Rather than infecting their airways, flu viruses typically infect the guts of birds; the viruses are then shed in bird droppings.
Bird flu viruses are well adapted to infecting their avian hosts and reproducing quickly inside them. Those adaptations make them ill-suited to spreading among humans.
When a flu virus hitches a ride aboard a droplet and infects a new host, it sometimes invades a cell that’s already harboring another flu virus. And when two different flu viruses reproduce inside the same cell, things can get messy. The genes of a flu virus are stored on eight separate segments, and when a host cell starts manufacturing the segments from two different viruses at once, they sometimes get mixed together. The new offspring end up carrying genetic material from both viruses. This mixing, known as reassortment, is a viral version of sex. When humans have children, the parents’ genes are mixed together, creating new combinations of the same two sets of DNA. Reassortment allows flu viruses to mix genes together into new combinations, as well.
on very rare occasions, an avian influenza virus can pick up human influenza virus genes through reassortment. That can be a recipe for disaster, because the new strain that results can easily spread from person to person. And because it has never circulated among humans before, no one has any defenses that could slow the new strain’s spread.
Humans are not the only hosts who have picked up flu viruses from birds. Horses, dogs, and several other mammals have also picked it up. And in April 2009, the world became painfully aware that flu viruses also infect pigs. An outbreak of so-called swine flu jumped from pigs to humans. It first surfaced in Mexico and soon spread over the entire planet. The history of this particular flu strain, called Human/Swine 2009 H1N1, is a tangled tale of genetic mixing and industrialized agriculture. Pigs seem to have just the right biology for reassortment; some of their receptors can easily accept human flu viruses, while other receptors welcome bird flu.
Rabbits with Horns: Human Papillomavirus
This balance between host and virus has existed for hundreds of millions of years. To reconstruct the history of papillomaviruses, scientists compare the genetic sequence of different strains and note which animals they infect. It turns out that papillomaviruses infect not just mammals, such as humans, rabbits, and cows, but other vertebrates as well, such as birds and reptiles. Each strain of virus typically only infects one or a few related species. Based on their relationships, Marc Gottschling of the University of Munich has argued that the first egg-laying land vertebrates— the ancestor of mammals, reptiles, and birds—was already a host to papillomaviruses three hundred million years ago.
a 2008 study on 1,797 men and women found 60 percent of them had antibodies to HPV, indicating they had been infected with the virus at some
In 2006, the first HPV vaccines were approved for use in the United States and Europe. They all contain proteins from the outer shell of HPV, which the immune system can learn to recognize. If people are later infected with HPV, their immune system can mount a rapid attack and wipe it out.
The Infected Ocean: Marine Phages
Scientists can determine the history of genes by comparing the genomes of species that split from a common ancestor that lived long ago. Those comparisons can, for example, reveal genes that were delivered to their current host by a virus that lived in the distant past. Scientists have found that all living things have mosaics of genomes, with hundreds or thousands of genes imported by viruses.
Our Inner Parasites: Endogenous Retroviruses
The idea that a host’s genes could have come from viruses is almost philosophical in its weirdness.
[...]was one of the clues that led virologists to discover that some viruses cause cancer.
Scientists recognized that this new virus was in a class of its own. They called it an endogenous retrovirus—endogenous meaning generated within. They soon found endogenous retroviruses in other animals. In fact, the viruses lurk in the genomes of just about every major group of vertebrates,
foamy viruses infected the common ancestor of three-toed sloths and primates, which lived a hundred million years ago.
Over millions of years, our genomes have picked up a vast amount of DNA from dead viruses. Each of us carries almost a hundred thousand fragments of endogenous retrovirus DNA in our genome, making up about 8 percent of our DNA. To put that figure in perspective, consider that the twenty thousand protein-coding genes in the human genome make up only 1.2 percent of our DNA.
Heidmann and other researchers have found that a human endogenous retrovirus gene plays a crucial role in that fusion. The cells in the outer placenta use the gene to produce a protein on their surface, which latches them to neighboring cells. In our most intimate moment, as new human life emerges from old, viruses are essential to our survival. There is no us and them—just a gradually blending and shifting mix of DNA.
The Young Scourge: Human Immunodeficiency Virus
Little did they know that they were publishing the first observations of what would become the greatest epidemic in modern history.
HIV belongs to a group of viruses—including influenza—that are very sloppy in their replication. They create many mutants in very little time. These mutants provide the raw material for natural selection to act on, producing viruses that are better and better adapted. Within a single host, natural selection can improve the ability of viruses to escape detection of the immune system.
Different people carry different variations in the genes for human leukocyte antigens. Goulder and his colleagues found that most of the HIV in each country carried mutations to the most effective human leukocyte antigens in that country’s population. Their findings tell us that HIV is rapidly adapting to the variations in human immune systems around the world. That is sobering news to those who are trying to build HIV vaccines. If a vaccine ever succeeds in boosting an effective immune response in people, HIV might well evolve a way to escape.
Becoming an American: West Nile Virus
infected bird could not have triggered a nationwide epidemic. The viruses needed a new vector to spread. It just so happens that West Nile viruses can survive inside 62 species of mosquitoes that live in the United States.
Moving from bird to mosquito to bird, West Nile virus spread across the entire United States in just 4 years. And along the way, people became ill with West Nile virus as well. About 85 percent of infections in the United States cause no symptoms. The other 15 percent of infected people develop fevers, rashes, and headaches, and 38 percent of them have to go to a hospital, where they stay for about 5 days on average. About 1 in 150 infected people end up developing encephalitis.
Between 1999 and 2008, U.S. doctors recorded 28,961 cases of West Nile virus. Of those victims, 1,131 died. Once
West Nile virus has fit so successfully into the ecology of the United States that it’s probably going to be impossible to eradicate. Unfortunately, doctors have no vaccine to prevent West Nile virus and no drugs to treat an infection. If you get sick, you can only hope that you are among the majority who suffer a fever and then recover.
Predicting the Next Plague: Severe Acute Respiratory Syndrome and Ebola
The Global Viral Forecasting Initiative is trying to change the way we fight viruses. Someday, somewhere, a virus we don’t know about is going to emerge as a major new threat to human health. We’ve seen it happen many times before, and so we know it will happen again. GVFI scientists think we’ll do a better job fighting that new virus if we can learn something about it in advance. To eliminate the advantage of surprise, GVFI scientists are looking for these viruses before they jump into humans.
Based on their experience with viruses such as HIV, scientists suspected that the SARS virus had evolved from a virus that infects animals. They began to analyze viruses in animals with which people in China have regular contact. As they discovered new viruses, they added their branches to the SARS evolutionary tree. In a matter of months, scientists had reconstructed the history of SARS. The virus started in Chinese bats.
The Long Goodbye: Smallpox
smallpox. But what a virus to wipe out. Over the past three thousand years, smallpox may have killed more people than any other disease on Earth.
About a third of people who got smallpox eventually died.
hosts. Between 1400 and 1800, smallpox killed an estimated five hundred million people every century in Europe alone.
and inoculated it into the arm of a boy. The boy developed a few small pustules, but otherwise he suffered no symptoms. Six weeks later, Jenner variolated the boy—in other words, he exposed the boy to smallpox, rather than cowpox. The boy developed no pustules at all. Jenner published a pamphlet in 1798 documenting this new, safer way to prevent smallpox. He dubbed it “vaccination,” after the Latin name of cowpox, Variolae vaccinae.
As vaccines grew popular, doctors struggled to keep up with the demand. At first they would pick off the scabs that formed on vaccinated arms, and use them to vaccinate others in turn. But since cowpox occurred naturally only in Europe, people in other parts of the world could not simply acquire the virus themselves. In 1803, King Carlos of Spain came up with a radical solution: a vaccine expedition to the Americas and Asia. Twenty orphans boarded a ship in Spain. One of the orphans had been vaccinated before the ship set sail. After eight days, the orphan developed pustules, and then scabs. Those scabs were used to vaccinate another orphan, and so on through a chain of vaccination. As the ship stopped in port after port, the expedition delivered scabs to vaccinate the local
Outbreak by outbreak, the virus was beaten back, until the last case was recorded in Ethiopia in 1977. The world was now free of smallpox.
Epilogue: The Alien in the Watercooler: Mimivirus
crystals, the same way they could crystallize salt or pure DNA. No one could ever crystallize a maple tree. In 2000, the International Committee on Taxonomy of Viruses declared that “viruses are not living organisms.” In the decade
Scientists don’t know what mimiviruses do with all of their genes, but some suspect that they do some rather lifelike things with them. Some of their proteins, for instance, look a lot like the proteins our own cells use to assemble new genes and proteins. When mimiviruses invade amoebae, they don’t dissolve into a cloud of molecules. Instead, they set up a massive, intricate structure called a viral factory. The virus factory takes in raw ingredients through one portal, and then spits out new DNA and proteins through two others. The viral factory looks and acts remarkably like a cell. It’s so much like a cell, in fact, that La Scola and his colleagues discovered in 2008 that it can be infected by a virus of its own. It was the first time anyone had found a virus of a virus. It was yet another thing that ought not to exist.
Drawing a bright line between life and nonlife can also make it harder to understand how life began in the first place. Scientists are still trying to work out the origin of life, but one thing is clear: it did not start suddenly with the flick of a great cosmic power switch. It’s likely that life emerged gradually, as raw ingredients like sugar and phosphate combined in increasingly complex reactions on the early Earth. It’s possible, for example, that single-stranded molecules of RNA gradually grew and acquired the ability to make copies of themselves. Trying to find a moment in time when such RNA-life abruptly became “alive” just distracts us from the gradual transition to life as we know it.
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