Eleven days after being bitten by one of her prairie dogs, a 3-year-old girl in Wisconsin on May 24, 2003 became the first person outside of Africa to be diagnosed with monkeypox. Two months later, her parents and 69 other people in the United States had suspected or confirmed cases of this disease, caused by a relative of the much deadlier smallpox virus. The monkeypox virus is endemic in parts of Africa, and rodents imported from Ghana had apparently infected captive prairie dogs, North American animals, when an animal dealer in Texas housed them together.
The outbreak now underway has affected more people outside of Africa than ever before: almost 1,300 cases as of June 7, across multiple continents, many of them men who have sex with men. But like the 2003 episode, today’s surge has raised a possibility that has researchers gulping: the monkeypox virus could permanently reside in wildlife outside of Africa, forming a reservoir that could lead to repeated human outbreaks.
No animal reservoir currently exists outside of Africa, but the 2003 US outbreak was close, some scientists suspect, especially since nearly 300 of the exposed Ghanaian animals and prairie dogs were never found. “We narrowly escaped monkeypox becoming established in a population of wild animals” in North America, suggests Anne Rimoin, an epidemiologist at the University of California, Los Angeles, who has long studied the disease in the Democratic Republic. of the Congo (DRC). In the end, however, surveys of wild animals in Wisconsin and Illinois never found monkeypox virus, none of the infected humans spread the disease to others, and concerns about this exotic outbreak evaporated.
Will North and South America, Europe, Asia and Australia, all of which have reported cases of monkeypox in this outbreak, be equally lucky this time?
Viruses frequently ping-pong between humans and other species. Although it is widely believed that COVID-19 was the result of SARS-CoV-2 jumping from a bat or other host to people, humans, in “reverse zoonoses,” have also infected white-tailed deer, mink, cats and dogs with the virus. A study in Ohio found SARS-CoV-2 antibodies in more than a third of 360 wild deer sampled. And in centuries past, when humans brought plague and yellow fever to new continents, those pathogens created reservoirs in rodents and monkeys, respectively, which then infected humans again.
As this monkeypox outbreak spreads, the virus has an unprecedented opportunity to establish itself in non-African species, potentially infecting humans and providing a greater opportunity for more dangerous variants to evolve. “Monkeypox reservoirs in wild animals outside of Africa are a scary scenario,” says Bertram Jacobs, a virologist at Arizona State University (ASU), Tempe, who studies vaccinia, the poxvirus that served as a vaccine against smallpox, and helped eradicate that devastating virus from humans
Public health officials in several countries have advised people who have monkeypox lesions to avoid contact with their pets until they heal. About 80% of the cases were in Europe, and the European Food Safety Authority said no pets or wild animals had been infected as of May 24. But he added that “close collaboration between human and veterinary public health authorities is needed to control exposed pets and prevent the disease from spreading to wildlife.”
The possibility that humans infected with the monkeypox virus will spread it to wildlife outside of Africa “justifies great concern,” says William Karesh, a veterinarian with the EcoHealth Alliance, who last week spoke about this possibility in a consultation on monkeypox research organized by World Health. Organization. For now, he says, the limited number of human cases lowers the odds. But domestic rodents are a particular concern, as are the large number of wild rodents (they make up 40% of all mammals) that frequently raid the garbage and could be infected by contaminated waste. “That’s a great opportunity,” he says.
Studies have yet to identify the African reservoir of the monkeypox virus. Although a laboratory in Copenhagen, Denmark, in 1958 first identified it in research monkeys from Asia, scientists now believe the primates captured it from an African source. All human cases since the first was reported in 1970, in the Democratic Republic of the Congo (then Zaire), could be linked to the virus that spread from animals in Africa.
So far, however, only six wild animals trapped in Africa have produced the virus: three rope squirrels, a Gambian rat, a shrew and a sooty mangabey monkey. Antibodies against monkeypox virus are more abundant in African squirrels. “We still don’t have a good understanding of the current reservoir other than rodents,” says Grant McFadden, a poxvirus researcher who also works at ASU.
But it is clear that monkeypox can infect many other types of animals in the wild and in captivity. A 1964 outbreak at a zoo in Rotterdam, the Netherlands, sickened giant anteaters, orangutans, gorillas, chimpanzees, a gibbon and a marmoset. Researchers have intentionally infected many laboratory animals, including rabbits, hamsters, guinea pigs, and chickens, although the virus does not reliably cause disease in several of them.
For many viruses, a lock-and-key relationship between viral surface proteins and receptors on host cells determines which animals it can infect; the spike protein of SARS-CoV-2, for example, attaches to angiotensin-converting enzyme 2, a protein that adheres to a variety of cells in humans, mink, cats, and many other species. But poxviruses do not appear to require host-specific receptors, allowing many to infect a wide range of mammalian cells. Vaccinia, the smallpox vaccine virus, can even infect fruit flies as well as cows and people, says David Evans, a poxvirus researcher at the University of Alberta, Edmonton. Bernard Moss, a virologist at the US National Institute of Allergy and Infectious Diseases (NIAID), has postulated that some poxviruses have proteins on their surfaces that form a “hydrophobic face,” an area that repels moisture. water and can bind nonspecifically to hydrophilic cell membranes. and start the infection process.
But whether a poxvirus can copy itself and ultimately persist in one species to create a reservoir depends on how well it fends off host immunological attacks. Poxviruses have a relatively large complement of genes, around 200, with about half undermining the host’s immune response. “Some viruses run and hide or are stealthy, avoiding direct contact with elements of the immune system,” says McFadden. “Poxviruses in general rise up and fight back.”
Their defense against host immunity appears to be largely dependent on a family of genes scattered around their genomes that encode little-known proteins that contain domains known as ankyrin repeats. The poxvirus proteins that contain these repeats act like “molecular flypaper,” Evans says, attaching themselves to host proteins involved in coordinating the immune response. “Orthopoxviruses have these arrays of ankyrin repeats, and most of them, we don’t really know what they’re targeting,” says Evans. “But the bottom line is that they probably hold the key to trying to understand why some of these viruses have the host range that they do.”
Variola, the smallpox virus, appears to have lost many of these immune-evasion genes. It only persists in humans and has no animal reservoir, so the global vaccination campaign could eradicate it. Monkeypox is clearly more promiscuous. But the many questions that remain about it mean it is not known whether it will create reservoirs in non-African wildlife. “One of the challenges has been a lack of interest,” says Lisa Hensley, a microbiologist with the US Department of Agriculture who began researching monkeypox in 2001 as part of a US Army lab.
Hensley, who worked on monkeypox at NIAID for nearly a decade and collaborated with Rimoin, urges people to keep an open mind about how the virus behaves and what it might do next. “We’re acknowledging that this is a disease that we need to be concerned about and that we really don’t know as much as we think we do.”
Source: www.science.org