The Urgent Mystery of Where Viruses Hide

Everything comes from somewhere. Dangerous new viruses typically come from animals.

Human influenza viruses? Those come from wild aquatic birds. Hantaviruses come from rodents. Mpox virus also comes from rodents, including squirrels, which is one reason it’s no longer called monkeypox virus. The pandemic-causing form of H.I.V. came from chimpanzees.

There are reasons for this pattern. Viruses can replicate only in the cells of cellular creatures (animals, plants, fungi, microbes) and, because we humans are animals ourselves, animal viruses most readily adapt to infect us. This connection is worth remembering as we deal with the continuous onslaught of newly emerging and re-emerging viruses. Identifying the animal source of a virus allows disease scientists to infer how and where the transfer into humans occurred, and that inference can guide measures to assure that it doesn’t happen again.

In 1998, for instance, a new virus that would eventually be named Nipah began killing people — mostly ethnic Chinese pig farmers — in western Malaysia. Tracing the virus to its reservoir host, a large fruit bat, led to an intricate, chilling recognition: that fruit trees planted overshadowing large hog lots attracted those bats, which dropped sucked-upon fruit pulp, containing their virus-laden saliva, to the delectation of pigs below. Infected pigs passed the virus along to pig farmers, an occupation dominated by non-Muslim males of Chinese extraction because Malaysia is a predominantly Muslim country. Deforestation of the bats’ natural habitat, rich with wild fruiting trees, had contributed to their migration toward orchards. Forest loss is difficult to fix, but protecting against future outbreaks of Nipah virus in Malaysia was almost as simple as separating the orchards from the hog lots.

But if scary new viruses come from animals, then ebolaviruses come from — where? Ebola and its near cousins have caused dozens of separate outbreaks in Central and West Africa over the past 50 years, at least a dozen of those in the Democratic Republic of Congo. A current outbreak in the eastern part of the country, the second-biggest in history, has exceeded 7,400 cases, with over 3,600 deaths. Common knowledge has it that ebolaviruses too come from bats. But that common “knowledge” isn’t supported by good evidence.

I speak of “ebolaviruses” to be accurate, because there are five of them known to infect humans: the Ebola virus itself (by far the most notorious), the Bundibugyo virus (the one now raging in Congo), the Sudan virus, the Tai Forest virus and the Reston virus (the one that caused frantic concern among disease responders in Reston, Va., in 1989, killing imported monkeys but leading to no severe human disease). The first two of those five have been the most horrific.

The kind of animal in which a virus abides over time, often inconspicuously, is known as the reservoir host. When the virus passes from that animal into a human, the event is called spillover. Then perhaps the virus adapts well to its human host, acquiring new capacities, including maybe an improved ability to transmit from one human to another. Reservoir host, spillover, adaptation, transmission: These are the ABC’s of viral ecology and evolution, crucial to consider for the control of outbreaks. But for the prevention of outbreaks, arguably the most important question, at least initially, is the identity of the reservoir host. Where does this virus hide, when it’s not infecting and killing humans?

The gold-standard evidence for identifying a reservoir host is to take a tissue or blood sample from a seemingly healthy animal and detect active virus within it. After 50 years of efforts, such evidence has never been found, in any kind of animal, bat or otherwise, for Ebola. Bats are a good guess, but still only a guess. As one group of experts wrote in 2020, most outbreaks of Ebola virus begin with a single spillover into the human population “from an unknown reservoir by unknown means.”

The first known Ebola outbreak occurred in 1976 in northern Zaire (now Congo). The first patient had traveled through the region, eating some antelope and smoked monkey meat. Did this implicate forest antelope or monkeys as the source of the new virus? Not necessarily. The outbreak ended after 11 gruesome weeks, with a count of 318 cases and 280 deaths. No other known cases of Ebola virus disease occurred for a year. Had the virus been exterminated? No. Where had it gone? Well, it hadn’t exactly gone anywhere; it didn’t spill back from its human victims into the forest (so far as anyone knows). It merely remained present in its original source: some animal host, not then identified, and not yet.

A year later Ebola resurfaced, killing a 9-year-old girl. “How the girl contracted the ebolavirus and where the virus originated from remains unclear,” wrote the virologist and virus historian Jens H. Kuhn, in his 2008 history of the ebolaviruses and their relatives. After that, Ebola disappeared again. There were no confirmed cases anywhere for 17 years. Then, between 1994 and 1996, seven outbreaks occurred in Gabon, each one apparently from an independent spillover. Six of the seven happened at gold-mining towns in forested areas near the border with Cameroon, where some residents reported seeing dead chimpanzees, dead gorillas and dead bush pigs in the forest. Handling such carcasses may have led to the outbreaks.

Does that implicate apes or bush pigs as the ultimate origin? No, because a reservoir host by definition is a creature in which the virus has reached a live-and-let-live accommodation. Both chimps and gorillas are eliminated as possible reservoir hosts of Ebola because they are fatally susceptible to the virus themselves. Thousands of gorillas in Central Africa, and similar numbers of chimps, are believed to have died from it.

I walked 50 miles through the forest in that area of northern Gabon, four years after the 1996 outbreak, and saw a remarkable absence of gorillas in their usual habitat. My companions and I knew that the Ebola virus was there somewhere, around us or above us, in some kind of animal — a bat, a duiker, a rat, a spider? — but we didn’t know which. We kept walking, and our expedition leader reminded the cook to put nothing found dead into the evening campfire stew.

What if scientists do solve the mystery of Ebola’s reservoir? There can be important applications of that knowledge to public health: strong regulations against hunting or selling the identified animal as food (let alone exporting it as a delicacy); warning signs in villages and markets, alerting people to the danger lurking in fresh or smoked carcasses of that animal; other warnings or restrictions to prevent people from living or farming anyplace where the animal is abundant. Knowing the reservoir host would also aid in tracing each outbreak to its index case — its patient zero — and in turn help illuminate and control the outbreak’s spread.

In the meantime, the Ebola virus comes and goes. It comes to humans from spillovers, and it seems to go away when an outbreak ends. Some human-infecting animal viruses are known to spill over into humans and spill back into nature. The Covid virus has spread somehow from human carriers into white-tailed deer across the American Midwest. But there’s no evidence that Ebola virus has ever spilled back into the forest. Under natural circumstances, the outbreak lineage comes to a dead end when the last human patient recovers or dies.

The Ebola virus doesn’t need to spill back. It abides in its reservoir host, and awaits its next opportunity. A virus can’t climb out of a bat or a monkey and fly off in search of human prey. It can only spill over. If humans left the reservoir host alone — not hunting it, not capturing it, not eating it, not exporting it live, not disturbing its forest habitat — the virus wouldn’t re-emerge in humans. It would remain where it is, harming no one. But of course that’s not what happens. And when viruses spill, they often spill into us, because the human population is such a big, busy target.