DOCTORS may be fretting about concurrent outbreaks of flu and covid-19 this winter,聽but some virologists are worrying about another scenario: a Frankenvirus.
SARS-CoV-2, the virus that causes covid-19, almost certainly originated from the hybridisation of two different coronaviruses. The details remain hazy, but the virus鈥檚 genome sequence suggests that this about a decade ago. The bat was simultaneously infected with two closely related coronaviruses, which merged into a new one.
Such recombination isn鈥檛 unusual for coronaviruses. 鈥淚f you look in the family tree of coronavirus, there鈥檚 recombination everywhere,鈥� says virologist Samuel D铆az-Mu帽oz at the University of California, Davis.
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It occurs for two reasons. First, coronaviruses are tolerant to co-infection. Unlike many other viruses, they allow co-infection of the same cell by other viruses.
Second, the way coronaviruses replicate their genomes makes hybridisation not just possible but likely. They are RNA viruses, which usually have very high rates of mutation 鈥� the highest rate of any known biological entity 鈥� because the enzymes that copy their RNA don鈥檛 have a proofreading function. A high mutation rate can allow a virus to rapidly evolve resistance to the host鈥檚 immune response.
Coronaviruses are the exception, because their replicase enzymes do proofread. SARS-CoV-2 has proved very resistant to mutation. According to D铆az-Mu帽oz, only six mutants have emerged thus far.
The variability in coronaviruses comes from something else: recombination. Their replicase enzymes frequently jump from one part of the RNA template to another. This makes them adept at remixing their own genomes to create variation, and also allows them to steal genetic material from other closely related coronaviruses. 鈥淚t is one of the things that facilitates jumping from one species to another. I think there鈥檚 no doubt that recombination in a bat was involved in the emergence of SARS-CoV-2,鈥� says D铆az-Mu帽oz. The fear is that it could now happen again, inside a human.
Research by Huiguang Yi at the Southern University of Science and Technology in Shenzhen, China, implies that . He has analysed 84 published SARS-CoV-2 genome sequences from human cases and found some that could only have formed through recombination.
There are also many including influenza, rhinovirus, respiratory syncytial virus and the seasonal coronaviruses that cause common colds.
This latter class are especially concerning, because they are quite closely related to SARS-CoV-2 and could potentially hybridise with it.
There are four of these seasonal coronaviruses in general circulation. There is also the original SARS virus, which caused an epidemic from 2002 to 2004. It is no longer in general circulation but virologists . Finally, there is the MERS coronavirus, which emerged in 2012 and still circulates at low levels. The fear is that a human co-infected with SARS-CoV-2 and a second coronavirus could be a crucible for the creation of a new virus, and even another pandemic.
A caveat is needed, however. In medical circles, co-infection means simultaneous infection of an individual host by two or more pathogens, not necessarily of the same cell within that host. We don鈥檛 yet know whether cellular co-infection occurs with SARS-CoV-2, says D铆az-Mu帽oz. But from what is known about coronaviruses, it is likely that it does.
鈥淲e worry about flu, but we should be paying more attention to the seasonal coronaviruses,鈥� says D铆az-Mu帽oz. 鈥淭hey are flying under the radar. Looking at what is going to happen with seasonal corona is one of the most important questions right now.鈥�
It isn鈥檛 known whether SARS-CoV-2 could recombine with a common coronavirus, but we can鈥檛 rule it out. 鈥淭o effectively combine the genomic material of two viruses is more complicated if the viruses are very different,鈥� says Ra煤l Rabad谩n at Columbia University in New York. 鈥淚f there is a co-infection between a common coronavirus and SARS-CoV-2 it is unlikely, although not impossible, that the potential recombinants will be viable.鈥�
鈥淲e worry about flu, but we should be paying more attention to the seasonal coronaviruses鈥�
Yi told New 杏吧原创 that he isn鈥檛 especially worried about a recombination event between SARS-CoV-2 and a cold-causing seasonal coronavirus, because their genomes aren鈥檛 closely related enough. However, the SARS and MERS viruses, or as yet unknown closely related coronaviruses, are a different story. SARS is the most genomically similar and hence the most dangerous, he says.
That sounds worrying, but a hybrid virus wouldn鈥檛 necessarily be worse than SARS-CoV-2, says D铆az-Mu帽oz. It could combine less virulent features of the two parent viruses, and become a mild respiratory virus like the common cold. 鈥淭hat may be evolutionarily advantageous to the virus. If people are no longer sheltering in place, it could spread more easily.鈥�
Even if a mash-up is unlikely, recombination in SARS-CoV-2 is still a huge concern, says Yi. It generates genetic variation that could make the virus more virulent, drug-resistant or better able to evade our immune system. It could also render diagnostics based on RNA assays useless. Doctors and disease control specialists should be concerned about these possibilities, he says.
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