Why do we find the middle host of the virus? To find out this, you understand a lot of problems.

The outbreak of pneumonia caused by the new coronavirus (SARS-CoV-2) in Wuhan, Hubei Province, at the end of 2019 has touched the hearts of the people of the whole country and once again pushed virological research and prevention and control to the forefront. The best way to eliminate fear is to face fear, and today we start with the concept of the host of the virus and talk about how the scandalous virus has entered human society from nature.

众所周知,病毒无法独立生长和复制,只能在宿主的活细胞内进行自我复制。

A virus host is a creature that provides an environment for a virus to survive. Viruses acquire the material and energy needed for life’s activities through the energy and metabolic system, thereby amplifying in the host body, and the host carrying the virus can spread the virus in a variety of ways.

Depending on the route of the virus’s propagation, the host can be divided into natural, intermediate, and end-host.

These three sounds simple and unpretentious names, in fact, implied “university questions.”

Is the bat really “a hundred poisons not to invade”? Are natural hosts so “powerful”?

First, natural host refers to organisms in nature that provide a place for nourishment and replication of viruses, except humans, and are the living environment in which viruses naturally inhabit and reproduce (in this case only for animal viruses).

Bats, for example, are known as the world’s top ten most dangerous viruses, bats are at least six of the natural hosts (Marburg virus, Ebola virus, rabies virus, SARS coronavirus, Hendra virus, Nipa virus), called “poison”.

However, bats have been able to keep up with these viruses for a long time and become the “condensate” of highly pathogenic diseased diseases, mainly because bats have evolved two “superpowers”.

(1) Bats are the only mammals that can fly. During the flight, the bat’s body temperature can be as high as 40 degrees Celsius. While most viruses are killed, a small number of viruses evolve, no longer afraid of the immune system’s “fever and enemy strategy.”

(2) The study found that bats have less sensitivity to identifying foreign bodies than other mammals, and that attacks on viruses do not trigger an excessive immune response, so bats are far more symbiotic with the virus than other mammals.

So does this mean that viruses tend to coexist peacefully with natural hosts?

In fact, in addition to bats, there are indeed other situations where natural hosts coexist peacefully with parasitic viruses, which often do not exhibit obvious clinical symptoms, but this is not a common phenomenon.

Viruses that continue to grow in the host body often damage the host, making it sick and even dead, just as seemingly powerful bats can die from rabies infections.

At the same time, the host is not just passively receiving the damage from the pathogen, its own immune system has the ability to actively resist, moderate and foreign invasion. If the host’s resistance is strong, the pathogen is difficult to invade or quickly be eliminated or eliminated after invasion.

Why do we find the middle host of the virus? To find out this, you understand a lot of problems.

Chinese chrysanthemum manta rays in a cave in Yunnan Province (Photo: Zhang Libiao/Guangdong Institute of Biological Resources Application)

There are more than 10 kinds of SARS in an intermediate host like this!

The intermediate host, as the name implies, is the host in the middle stage, which can provide temporary nutrition and protection for the virus, and the intermediate host often acts as a vector to “transport” the virus to the “end point”, that is, the final host.

It should be noted that the intermediate host is a relative concept, not an absolute concept. An intermediate host can include multiple species.

In the case of SARS coronavirus, studies have shown that more than 10 mammals are susceptible to the virus, and it is now widely believed that fruit beavers are the main intermediate hosts of its transmission because early infected people have been in close contact with beavers. And the SARS coronavirus isolated from the fruit beaver is highly homogenous with the SARS virus isolated in humans. There is also evidence that animals other than beavers are involved in the spread of SARS coronavirus to humans.

Is the new coronavirus coming from bats?

At present, the new coronavirus (SARS-CoV-2) that is ravaging the country is under way. On January 23, 2020, Shi Zhengli’s team at the Wuhan Virus Research Institute of the Chinese Academy of Sciences published an article on the bioRxiv preplate platform reporting that SARS-CoV-2 has a 96% consistency with the coronavirus sequence in a bat.

In the evolutionary tree location, SARS-CoV-2 is adjacent to the SARS coronavirus and SARS-like coronavirus groups, but does not belong to the SARS and SARS virus groups. Since the evolutionary neighbors of the new coronavirus have been found in all types of bats, it is speculated that their natural host may also be bats.

Related reports, the network on eating bats to get pneumonia video, views on a time very much on the dust, caused the national attention.

In fact, as long as you understand the difference between a virus in a natural host and a middle host, you won’t believe this easily.

Why do we find the middle host of the virus? To find out this, you understand a lot of problems.

At this stage, although the possibility of virus transmission directly from a natural host to humans cannot be completely ruled out, the odds can be said to be slim in fact.

Studies have shown that progenitorviruses present in natural host bodies cannot effectively use human susceptibility cell receptors and open the intrusion portal, which is the main factor limiting the direct transmission of protovirus to humans.

Why do we have to find the middle host?

This raises another important question, why do we have to find the middle host?

According to our current understanding of viruses, if a virus that was not previously infected with humans, and wanted to become able to infect humans, there must be intermediate hosts that led to its rapid evolution, which is divided into gene recombination and gene adaptability mutations. Gene recombination here refers to the physical exchange of heritage substances when two or more viruses replicate within the host cell, which can lead to new phenotypes.

We take SARS-CoV-2’s nearest neighbor SARS coronavirus as an example, the original bat carrying SARS-like coronavirus can not infect humans, but the bat SARS-like coronavirus and another can infect human coronavirus may be jointly infected with the middle host, in the middle host’s body, Bat SARS-like coronavirus “steals” the skills of infected people, they recombination to obtain another virus ACE2 (SARS coronavirus receptor) binding site, through which they become able to bind to human susceptibility cells.

Another form of evolution is continuous evolution that does not depend on recombination. Coronary viruses in bats can acquire or improve the ability of the proviral to bind to human ACE2 by adapting (i.e. point mutations) in more than one intermediate host before it can effectively infect a person. The researchers found that there were at least three highly variable genomic regions between SARS coronavirus escloser and SARS-like coronavirus, suggesting that the second evolutionary mechanism was more likely.

This also explains why SARS coronavirus can cause a human pandemic, while the closely related bat SARS-like coronavirus can not.

Coronavirus as an RNA virus, its genome replication required RNA replication enzyme lack of correction function, so the error rate of replication is high gene mutation rate, coupled with different coronavirus RNA and RNA recombination rate is also very high, so coronavirus mutation is not difficult.

Therefore, it is particularly important to find the intermediate host of SARS-CoV-2.

It is the intermediate host that provides the virus with the opportunity to mutate and develop and touch humans, and only by isolating the intermediate host is the source of infection is truly isolated.

Since the outbreak of new coronary pneumonia, the research on sars-CoV-2 intermediate host has been widely discussed. On January 24, 2020, Professor Zhu Wai-ball, a professor in the Department of Biomedical Engineering at Peking University’s School of Engineering, published a research paper on the bioRxiv preplate platform, using the VHP (Viral Host Prediction) method developed based on deep learning algorithms to suggest that otters may be intermediate hosts of SARS-CoV-2.

Immediately after, South China Agricultural University announced on February 7: After a number of research teams jointly identified through virus isolation identification and molecular biology testing methods found that the virus isolated from pangolins and the current infected human strains of the series similarity of up to 99%, suggesting that pangolin is a potential intermediate host of SARS-CoV-2.

Why do we find the middle host of the virus? To find out this, you understand a lot of problems.

Otters (Photo Source: Open Source)

Why do we find the middle host of the virus? To find out this, you understand a lot of problems.

Pangolins (photo source: https://www.naturepl.com/stock-photos-manis-pentadactyla-nature-image00551471.html)

Although, the current study of intermediate hosts has not been conclusive, but so far, we can roughly sort out SARS-CoV-2 from nature into human society a possible route: a coronavirus parasitic in the natural host bat infected in some way, such as otters, pangolins and other potential intermediate hosts. The progenitor virus is constantly adapted to mutations or genetic recombination with other coronaviruses in the intermediate host body, thus gaining the ability to infect humans. When an infected intermediate host enters the market, it transmits the virus to someone with whom he has been in close contact.

The road ahead is long, but we never lack the courage to face difficulties.

Is this the end of the story? In fact, it’s far from.

After the discovery of a new type of human-animal co-disease that can infect people, the top priority of prevention and control is undoubtedly to determine whether the new virus has the ability to spread from person to person, that is, the story of the virus occurring in the end-host body.

In fact, when an animal-derived virus evolves to acquire the ability to infect humans, it does not necessarily mean that it can spread among people.

In the case of the H5N1 subtype avian influenza virus, which we know as a subtype, H5N1 is transmitted from its natural host, wild waterfowl, to poultry, and from poultry to very few humans, without causing a pandemic of disease, because H5N1 has not been adapted to evolution in the human body.

Resusiting with SARS coronavirus in 2003, molecular epidemiological analysis showed that human SARS coronavirus isolates could be divided into 3 groups according to the early, medium and late stages of the outbreak, and the early isolation strains were more closely related to animal strains.

That is to say, the virus into the human body will continue to mutate to better adapt to the human environment, and eventually gain the ability to spread widely in the population, so that the virus is completed its ultimate “mission.”

From the deep underground caves to the sparsely-visited Sahara Desert to the deep-water waters of the Antarctic ice sheet, the newly discovered viruses are everywhere, and the sheer number of giants is destined to be a protracted battle between humans and viruses.

Since the outbreak of new coronapneumonia, we are saddened by the rising number of confirmed cases and deaths, we are moved by the national justice of one side with the support of all sides, and we admire the selfless dedication of front-line medical staff and researchers! I believe that with the joint efforts of the people of the whole country, we will eventually win the battle of the epidemic!