Concerns over human ape epidemic could spread virus to animals outside Africa

On May 24, 2003, in Wisconsin, a 3-year-old girl became the first person outside of Africa to be diagnosed with monkey disease eleven days after being bitten by one of her pets. Two months later, his parents and 69 other people in the United States suspected or confirmed cases of the disease, which was caused by a relative of the deadly smallpox virus. The smallpox virus is endemic in parts of Africa, and rodents from Ghana have infected captive field dogs and North American animals when they were put together by a Texas animal distributor.

The current epidemic has hit people outside Africa more than ever – as of June 7, there were about 1,300 cases on several continents, most of them between men and women who had sex. However, as with the 2003 episode, today’s developments have increased the chances of researchers swallowing: The monkey smallpox virus may be endemic to wildlife outside Africa, creating a reservoir that could lead to a recurring human epidemic.

Outside Africa, there are currently no animal reservoirs, but the 2003 outbreak in the United States was a recent challenge, with some scientists suspect that nearly 300 animals, especially from Ghana, and wild dogs have never been found. We got rid of smallpox in a wild animal population in North America, ”said Anne Rimoin, an epidemiologist at the University of California, Los Angeles, who has long studied the disease in the Democratic Republic of the Congo. Finally, wildlife studies in Wisconsin and Illinois have never found a monkey smallpox virus, and none of those infected have transmitted the disease to others, raising concerns about this exotic epidemic.

Will North and South America, Europe, Asia, and Australia — those affected by the monkey epidemic — be just as happy this time around?

Viruses often play ping-pong between humans and other species. Although KOVID-19 SARS-CoV-2 is thought to have originated from bats or other host jumps on humans, humans have also contracted white-tailed deer, mink, cats and dogs in “reverse zoonoses.” virus. A study in Ohio found antibodies to SARS-CoV-2 in more than a third of 360 wild deer. In the past, when humans brought plague and yellow fever to new continents, the pathogens formed reservoirs in rodents and monkeys, which later re-infected humans.

As this smallpox epidemic spreads, the virus has an unprecedented potential to spread to non-African species, making it more susceptible to humans and allowing the evolution of dangerous variants. “Monkeys outbreaks in wildlife outside Africa are a dangerous scenario,” said Bertram Jacobs, a virologist at Arizona State University (ASU), who studied the vaccine, which served as a vaccine against smallpox and helped eradicate the deadly virus. people.

Public health officials in a number of countries have advised people with smallpox to avoid contact with pets until they have recovered. About 80% were in Europe and the European Food Safety Authority said as of May 24, no pets or wildlife had been infected. But he added, “Close cooperation between people and veterinary public health authorities is needed to manage pets and prevent the spread of the disease to the wild.”

The possibility of people infected with the smallpox virus spreading it to wildlife outside Africa is “a serious concern,” said William Caresh, a veterinarian with the EcoHealth Alliance, who spoke about the possibility last week at a World Health Organization (WHO) consultation on smallpox. To organize. So far, he said, the limited number of people would reduce the chances. However, domestic rodents are of particular concern, as the number of wild animals – they make up 40% of all mammals – often captures waste and can become infected with contaminated waste. “It’s a great opportunity,” he says.

Studies have not yet identified the African reservoir of the monkey smallpox virus. Also a laboratory in Copenhagen, Denmark, It was first identified in 1958 in a study of Asian monkeys, and scientists now believe that primates caught it from an African source. Since the first outbreak in the Congo (then Zaire) in 1970, all human cases may have been caused by an animal virus in Africa.

So far, however, only six wild animals in Africa have been infected: three ropes, a Gambian rat, a moth, and a monkey. Antibodies to the smallpox virus are most common in African swamps. “We still don’t understand the current reservoir very well, except for rodents,” said Grant McFadden, a poxvirus researcher based at ASU.

However, it is clear that smallpox can infect many other species of wild and captive animals. In 1964, large ants, orangutans, gorillas, chimpanzees, gibbons, and marmots became ill at a zoo in Rotterdam, the Netherlands. Researchers have deliberately infected many laboratory animals, including rabbits, hamsters, guinea pigs, and chickens, but the virus does not cause disease in some of them.

For many viruses, the lock and key connection between the surface proteins of the virus and the receptors in the host cells determine which animals it can infect; For example, SARS-CoV-2 binds to spik protein, an angiotensin-converting enzyme 2, and a protein that grows in various cells in humans, mink, cats, and many other species. However, poxviruses do not seem to require specific receptors, which allows them to infect many mammalian cells. Vaccinia, the smallpox vaccine virus, can infect not only cows and humans, but also fruit flies, says David Evans, a researcher at the University of Alberta, Edmonton. Bernard Moss, a virologist at the National Institute of Allergy and Infectious Diseases (NIAID) in the United States, claimed that some poxviruses contain proteins that form a “hydrophobic surface” on the surface, which is a water-repellent area that can bind non-specific to hydrophilic cell membranes. and start the infection process.

However, whether the poxvirus can replicate itself and eventually survive in some form to create a reservoir depends on how well it resists the host’s immune attacks. Poxviruses have a relatively large complement of about 200 genes, and about half of them disrupt the host’s immune response. “Some viruses run, hide, or hide without being in direct contact with elements of the immune system,” McFadden said. “Poxviruses basically get up and fight.”

Their defense against host immunity is based on a family of genes scattered around their genomes that encode poorly understood proteins, including domains known as ankylosing spondylitis. Poxvirus proteins that contain these replicates act as “molecular fly paper,” Evans said, referring to proteins that coordinate the immune response. “Orthopoxviruses have recurrent arrays of ankylosing spondylitis, and we don’t know what most of them are aimed at,” Evans said. “But most importantly, those who try to understand why some of these viruses have their host range hold the key.”

Variola, the smallpox virus, seems to have lost most of these immune escape genes. It is only stored in humans and there is no reservoir for animals, so a global vaccination campaign can destroy it. Monkeys are more corrupt. But many questions about it say nothing about whether it forms reservoirs in non-African wildlife. Lisa Hensley, a microbiologist with the U.S. Department of Agriculture who began studying smallpox as part of a U.S. Army lab in 2001, says one of the challenges was a lack of interest.

Hensley, who has worked with NIAID for nearly a decade on monkey disease and worked with Remoin, encourages people to think openly about how the virus is behaving and what it can do next. “We understand that this is a disease we need to worry about and that we can’t know as much as we think we know.”

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