How virus detectors locate the origins of an outbreak and why it is so complicated


EFor a long time, there has been a major outbreak of disease, one of the first questions scientists and the public ask is, “Where did this come from?”

To predict and prevent future pandemics like COVID-19, researchers must find the source of the viruses that cause them. It is not a trivial task. He origin of HIV it was not clear until 20 years after it spread around the world. Scientists do not yet know the origin of Ebola, although they do caused periodic epidemics since the 1970s.

As a expert in viral ecology, I am often asked how scientists trace the origins of a virus. In my work, I have found many new viruses and some known pathogens that infect wild plants without causing any disease. Plant, animal or human, the methods are largely the same. Tracking the origins of a virus involves a combination of extensive fieldwork, thorough laboratory testing, and good luck.

Viruses jump from wild animal hosts to humans

Many viruses and other disease agents that infect people originate in animals. These diseases are zoonotic, that is, they are caused by animal viruses that jumped on people and adapted to spread through the human population.

It may be tempting to start searching for viral origin by testing sick animals at the site of the first known human infection, but wild hosts often show no symptoms. Viruses and their hosts adapt to each other over time, so viruses often do not cause obvious symptoms of disease until they have done so. jumped to a new host species. Researchers can’t just look for sick animals.

Another problem is that people and their food animals are not stationary. The place where the researchers find the first person infected is not necessarily close to where the virus originated.

In the case of COVID-19, bats were an obvious first place to look at it. They are hosts known to many coronaviruses and are the likely source of other zoonotic diseases such as SARS and MERS.

For SARS-CoV-2, the virus that causes COVID-19, the closest relative scientists have so far found BatCoV RaTG13. This virus is part of a collection of bat coronaviruses discovered in 2011 and 2012 by virologists at the Wuhan Institute of Virology. Virologists were looking for SARS – related coronaviruses in bats after SARS-CoV-1 pandemic in 2003. They collected fecal samples and bat throat swabs at a site in Yunnan Province about 1,500 kilometers from the Wuhan Institute laboratory, where they brought samples back for further study.

To test whether bat coronaviruses could spread to humans, the researchers infected monkey kidney cells and cells derived from human tumors with samples from Yunnan. They found that some of the viruses in this collection could they replicate in human cells, that is, they could potentially be transmitted directly from bats to humans without an intermediate host. However, bats and people do not come into direct contact very often, so there is likely to be an intermediate host.

Find the closest relatives

The next step is to determine what relationship a suspected wildlife virus has with what infects humans. Scientists do this by discovering the genetic sequence of the virus, which is to determine the order of the basic basic blocks, or nucleotides, which form the genome. The more nucleotides shared by two genetic sequences, the more closely they are related.

Genetic sequencing of bat coronavirus RaTG13 showed that it was over 96% identical and SARS-CoV-2. This level of similarity means that RaTG13 is a relatively close relative to SARS-CoV-2, confirming that SARS-CoV-2 probably originated in bats, but is still too far away to be a direct ancestor. There was probably another host who caught the bat virus and transmitted it to humans.

Because some of the first cases of COVID-19 were found in people associated with the Wuhan Wildlife Market, it was speculated that a wild animal from that market was the intermediate host between bats and humans. However, researchers i never found the coronavirus in market animals.

Similarly, when a coronavirus related to pangolins confiscated in an anti-smuggling operation in southern China, many concluded that SARS-CoV-2 had jumped from bats to pangolins to humans. He pangolin virus it was found to be only 91% identical to SARS-CoV-2, although it is unlikely to be a direct ancestor of the human virus.

To identify the origin of SARS-CoV-2, many more wild-type samples need to be collected. This is a difficult task: bat sampling is time consuming and requires strict precautions against accidental infection. Since SARS-related coronaviruses are found bats throughout Asia, including Thailand and Japan, is a very large barn looking for a very small needle.

Creation of a family tree for SARS-CoV-2

In order to sort out the puzzle of origins and viral movements, scientists must not only find the missing pieces, but also find out how they all fit together. This requires collecting viral samples of human infections and comparing these genetic sequences with each other and with other animal-derived viruses.

To determine how these viral samples relate, researchers use computer tools to build the virus’s family tree, or phylogeny. The researchers compare the genetic sequences of each viral sample and construct relationships by aligning and classifying genetic similarities and differences.

The direct ancestor of the virus, which shares the greatest genetic similarity, could be considered its father. Variants that share the same parent sequence but with enough changes to differentiate them are like siblings. In the case of SARS-CoV-2, the The South African variant, B.1.351, and the British variant, B.1.1.7, are brothers.

Building a family tree is complicated by the fact that different analysis parameters can give different results: the same set of genetic sequences can produce two very different family trees.

For SARS-CoV-2, phylogenetic analysis is particularly difficult. But tens of thousands of SARS-CoV-2 sequences they are now available, they do not differ enough from each other form a clear image of how they relate to each other.

The current debate: overflow of the wild host or the lab?

Could SARS-CoV-2 have been released from a research laboratory? Although current tests implies that this is not the case, recently 18 prominent virologists suggested that this question should be more researched.

Although it has been speculated that SARS-CoV-2 has been designed in a laboratory, this possibility seems very unlikely. When comparing the genetic sequence of wild-type RaTG13 with SARS-CoV-2, the differences are randomly distributed across the genome. In a designed virus, there would be clear blocks of changes they represent sequences introduced from a different viral source.

There is a unique sequence in the SARS-CoV-2 genome that encodes a portion of the spike protein that appears to play an important role in human infection. Interestingly, a sequence similar to the MERS coronavirus is found that causes a disease similar to COVID-19.

Although it is unclear how SARS-CoV-2 acquired these sequences, viral evolution suggests that they arose from natural processes. Virus accumulate changes either by genetic exchange with other viruses and their hosts, or by random errors during replication. Viruses that get a genetic change that gives them one reproductive advantage it would normally continue to transmit it through replication. That MERS and SARS-CoV-2 share a similar sequence in this part of the genome suggests that it evolved naturally in both and spread because it helps them infect human cells.

Where to go from here?

Finding out the origin of SARS-CoV-2 could give us clues to understand and predict future pandemics, but we may never know exactly where it came from. Regardless of how SARS-CoV-2 jumped on humans, it is now here and has probably come to stay. In the future, researchers will need to continue to monitor its spread and vaccinate as many people as possible.

Marilyn J. Roossinck, Professor of Plant Pathology and Environmental Microbiology, Penn State

This article is republished from The conversation under a Creative Commons license. Read the original article.

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