Monkeypox is transmitted between humans, and humans transmit COVID-19 to minks... Beware of the "virus interweaving" between animals and humans

The new coronavirus has not yet subsided, and monkeypox has resurfaced. Many new pathogens that disrupt human society come from the animal world. Why are such incidents increasing year by year? Why should we be wary of the "virus interweaving" between animals and humans?

Written by reporter Wang Xueying Edited by Ding Lin

New Media Editor/Li Yunfeng

The shadow of the COVID-19 epidemic has not yet dissipated, and a potential new epidemic has come into people's view.

According to the World Health Organization, monkeypox cases have been reported from many countries recently. As of May 21, 92 confirmed cases and 28 suspected cases of monkeypox have been reported in 12 countries and regions around the world. The WHO reminds that the discovery of monkeypox cases in countries outside Africa is "atypical". Experts predict that as the scope of monitoring expands, the number of global monkeypox cases may increase further in the future.

In addition to the rapid development of the epidemic, what worries people is the new changes in the monkeypox virus itself. Existing information proves that the monkeypox virus has now spread from person to person, which was generally considered rare in the nearly half a century before. From its first discovery in monkeys in 1958, to the diagnosis of the first infected human patient in 1970, to its direct transmission between people today, the monkeypox virus has once again reminded humans that pathogens do not have strict species "isolation zones".

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Monkeypox: From animal disease to zoonosis

In 1958, a group of crab-eating macaques shipped from Singapore to Denmark for polio vaccine research suddenly fell ill. Initially, the monkeys' abnormalities did not attract enough attention until they began to develop blisters that resembled smallpox symptoms. Scientists then isolated a special orthopoxvirus from the pox fluid of these monkeys and named it "monkeypox". At this time, the monkeypox virus was still at the stage of "animal virus".

Twelve years later, in 1970, a patient with a very special condition appeared in the Democratic Republic of the Congo in Africa. The 9-year-old boy seemed to be infected with smallpox, but his region had basically achieved "zero smallpox infection" as early as 1968 due to the promotion of vaccines. In this case, what was the boy infected with? What the researchers did not expect was that they extracted monkeypox virus from the boy's pox fluid sample - the world's first case of monkeypox infection showed that monkeypox had become a zoonosis.

At that time, human-to-human transmission of the monkeypox virus was uncommon. The main routes of transmission include close contact with respiratory secretions, skin lesions, or contaminated objects from an infected person. Face-to-face respiratory droplet transmission takes longer. As the World Health Organization sounded the monkeypox alarm, more African countries began to report cases of monkeypox. At first, most cases were concentrated in rural areas and around the rainforest in the Democratic Republic of the Congo, and later related cases began to appear in West Africa. However, with the exception of an outbreak in the Democratic Republic of the Congo in 1996, human monkeypox outbreaks have been relatively small and controllable, and cases have never "left Africa."

▲Between 1970 and 2017, monkeypox was mainly spread in parts of Africa. Compared with the monkeypox branch in West Africa, the monkeypox branch spreading near the Congo Basin has a higher mortality rate (Image source: World Health Organization)

However, the monkeypox outbreak in the United States in 2003 completely changed people's misconception of the virus's "geographic spread". Data show that this outbreak was the first report of human infection with the monkeypox virus outside of Africa, with a total of 53 confirmed cases involving six states in the United States, and the "source of the virus" was actually several Gambian giant rats and squirrels. They passed the monkeypox virus they carried to pet dogs and pet marmots that were fostered together, and some people were eventually infected because of close contact with these domestic pets.

Although monkeys were first discovered, the natural host of the monkeypox virus is not monkeys. Research evidence shows that although many species have been found to be infected with monkeypox virus, rodents may be the true reservoir host of the virus. Monkeys, like humans, are just hosts after the virus "spills over".

"It's really eye-opening to see (monkeypox virus) spread like this," said Anne Lemon, an epidemiologist at the University of California, in a recent media interview. Lemon, who has been studying monkeypox virus in Africa for more than a decade, believes that the monkeypox outbreak in multiple countries outside Africa almost simultaneously should attract the attention of scientists around the world. "We have never seen a situation like this before."

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Cross-species “spillover” and “backflow” of pathogens

There is a very important concept in infectious disease research, namely the "spill-over" phenomenon of pathogens.

Throughout the history of human development, many pathogens that have "caused chaos in the world" come from other animals, such as the human immunodeficiency virus (HIV) transmitted from primates to humans, and the avian influenza virus (such as H5N1, H7N9, etc.) transmitted from birds to humans... In recent years, many new pathogens that have disrupted human society have also come from the animal world.

(Image source: npr.com)

Take viruses as an example: in order for viruses in nature to spread and replicate in a host, they need a corresponding protein "key" to open a specific protein "lock" in the body. This "one key opens one lock" interaction limits the spread of most viruses to specific hosts.

While the virus is replicating in large quantities, it is also mass-producing the "keys" that can be used to open the door. However, there are always exceptions. The "process" of virus replication occasionally goes wrong, producing a few "keys" that are not so standard - there may be an extra tooth mark or one less tooth mark. Most of these mutations have no practical effect, but the exception is that some mutated keys happen to be able to open the protein "door lock" of another new host species.

If a virus with a mutation "key" infects a completely new species and spreads continuously within it, this process is called the virus "spillover". In this process, it is the occurrence of gene mutations that allows the virus to overcome the barriers between species and achieve cross-species transmission. This also makes it possible for some animal infectious diseases to become zoonotic diseases.

On the other hand, the cross-species transmission of pathogens is not a one-way street. Humans are not only infected by pathogens from animals, but also transmit their own diseases to animals. This process is called the "spillback" phenomenon of pathogens. In this process, animals infected by humans may become new bioreactors - pathogens will accumulate more mutations in order to adapt to new hosts. When the "secondary spillover" phenomenon occurs, these "renovated" pathogens may catch humans off guard again...

(Image source: nyt.com)

"After cross-species transmission occurs, the virus is usually able to quickly adapt to the new host." Simone Kraberg, an assistant researcher in the Department of Immunology and Pathology at Colorado State University, said that this repeated transmission "may further accelerate the evolution of the virus and lead to the emergence of more new strains."

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“Backflow” makes the virus hard to prevent

Compared with the overflow of pathogens, their backflow is more troublesome. Among the many pathogens, viruses may be the most prone to backflow.

Earlier this year, a pet store in Hong Kong, China, had a confirmed case of COVID-19. However, researchers from the University of Hong Kong discovered during routine testing that the source of the outbreak might be pet hamsters. In sample and serum tests, researchers found that 8 of the 16 Syrian hamsters (golden hamsters) in the pet store and 7 of the 12 Syrian hamsters in the warehouse tested positive for COVID-19. Not only that, after sequencing the viral genomes of human infections and hamsters, researchers found that the Delta strain was the cause of the disease.

This incident once again reminds us that in addition to bats, which have always been "guarded against", rodents may also become natural reservoirs of the new coronavirus and may transmit the virus back to humans.

Recently, the emergence of the new coronavirus Omicron variant has pushed the global COVID-19 pandemic to another peak. Researchers have found that there are 35 mutations in the spike protein (S protein) of the Omicron strain, of which 7 mutations may make it better adapted to rodents. Some scientists speculate that these mutations are likely to occur in "special hosts" - the early new coronavirus underwent new mutations during the spillover from "humans to animals", resulting in the Omicron strain.

▲CT images show that experimental hamsters infected with the new coronavirus also have "ground-glass shadows" in their lungs similar to those of human patients (Photo source: University of Wisconsin-Madison)

The academic community has not yet identified the identity of this "special host", but the large number of similar virus spillover phenomena has long aroused widespread concern among scientists. Since the outbreak of the new crown epidemic, some animal groups have also been greatly impacted, one of which is mink.

As of the end of December 2021, the World Organization for Animal Health has recorded 625 cases of COVID-19 outbreaks in animals, with 17 species in 37 countries infected. During this period, more than 700,000 farmed minks died from the coronavirus, the highest number of animals to die from the virus. At the same time, many countries have also launched large-scale culling of farmed minks, with Denmark alone culling as many as 17 million... These "misfortunes never come singly" minks can not only be infected with the coronavirus by humans, but can also transmit the virus to humans. There is evidence that at least three variants of the coronavirus that can be confirmed to be associated with minks have appeared, among which the "Michigan mink variant" may have community transmission among humans.

At the end of 2020, Bu Zhigao's team at the Harbin Veterinary Research Institute of the Chinese Academy of Agricultural Sciences published a paper confirming that the new coronavirus can replicate and cause disease in mink species, and explained the mechanism behind the transmission of the new coronavirus from mink to humans. The researchers found that after minks were infected with the new coronavirus isolated from humans, the virus could replicate at high levels in the nasal cavity and lungs of minks, and cause pathological damage (including pulmonary thrombosis) in the upper and lower respiratory tracts of minks. This process is very similar to the pathological damage after humans are infected with the new coronavirus. At the same time, Bu Zhigao's team also found that the new coronavirus can not only be transmitted efficiently between minks through respiratory droplets, but can also be transmitted asymptomatically, which is very similar to the transmission between humans.

(Image source: nyt.com)

"Every time the virus spreads between species, it changes," French epidemiologist Marisa Pere said in an interview with the media. "If the mutated virus is too different from the widely spread virus, it may mean that any newly developed vaccine or treatment will not meet expectations."

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Everyone is well, then it is a "sunny day"

In recent years, animal diseases have become more frequent infecting humans, and more and more new epidemics are labeled "zoonotic diseases." In response to this trend, Kate Jones, an expert in the interaction between ecosystems and human health at University College London, conducted an analysis. She counted 335 new diseases that emerged between 1960 and 2004 and found that 60.3% of them were zoonotic diseases and 71.8% of them originated from wild animals, and these proportions are increasing year by year.

A recent study published in Nature magazine pointed out that due to global climate change, more and more animal species are forced to leave their habitats and enter new environments, and this migration will also move their parasites and pathogens simultaneously. Scientists predict that the probability of new cross-species contacts will double in the next 50 years, especially in Africa, Asia and tropical regions with a wide variety of species, which may become the "cradle" of terrible epidemics caused by the "overflow" of more animal viruses.

"More and more evidence shows that in the coming decades, the world will not only get hotter, but there will also be more disease," said Gregory Albury, a disease ecologist at Georgetown University in the United States. As the main author of the Nature study, he believes that it is urgent for the world to strengthen monitoring of animal diseases and zoonotic diseases: "Humanity does not have much time to waste."

▲White-tailed deer in the United States and Canada were found to be infected with the new coronavirus. Most animals known to be infected with the new coronavirus are pets or captive animals, and it is relatively easy to detect and isolate these infected animals. Health experts say the real threat comes from wild animals (Image source: nature.com)

Unfortunately, compared with the research on spillover, people have not paid enough attention to the severity of spillover. For a long time, the "human-centered" way of thinking has determined that humans will not pay much attention to epidemics in animals. The few related studies are mainly focused on primates, large captive animals, endangered species, and domestic pets, and long-term scientific monitoring of wildlife diseases is relatively scarce. On the other hand, studying the chain reactions caused by the spillover of pathogens "from humans to animals" and genetic sequencing of animal pathogens are still relatively unpopular research.

Not only may spillover cause “secondary overflow” and endanger human health, but the wildlife populations affected by spillover (especially the more vulnerable ones) may also face greater and sometimes even catastrophic risks.

For example, there are only about 1,000 mountain gorillas left in the world, which is a rare species on the verge of extinction. In order to better protect this endangered population, some scientists have maintained long-term scientific monitoring of it. In 2009, people were surprised to find that a group of mountain gorillas in the Rwanda Wildlife Conservation Park showed symptoms of human metapneumovirus (hMPV) infection. The hMPV virus was also detected in the tissue sample of a dead gorilla, and it matched the tissue sample of an infected patient in South Africa.

As a respiratory pathogen, hMPV generally only causes flu-like infections in humans, but spillovers pose a serious threat to the health and survival of mountain gorillas. Mountain gorillas have died from hMPV infections at parks where outbreaks have occurred.

(Image source: vox.com)

Humans are not independent organisms. The ecological environment around us is closely related to human health and cannot be separated. As global climate change intensifies, more and more species are forced to become "climate immigrants". Some species that once "lived apart" and avoided harming each other will also collide with new "dangerous relationships". What "new surprises" will nature's "blind box" open next time? No one knows the answer, and no one wants to know.

Produced by: Science Central Kitchen

Produced by: Beijing Science and Technology News | Beijing Science and Technology Media

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