In July, Japan was hit by its largest COVID-19 wave yet. Driven by the introduction of the more infectious Delta variant, cases surged to a record of nearly 26,000 daily cases, over four times that of the wave before it. Then, as quickly as cases rose, they fell once again, and within two months of the peak, cases now rest at around 140 per day. Scientists are aware the rapid rise was due to the Delta variant, but they failed to understand how cases plummeted back down while other nations continue to battle against the virus.
Now, researchers from Japan’s National Institute of Genetics have proposed that the Delta variant may have fallen victim to its own success – the rapidly-mutating strain may have mutated itself into extinction within Japan. According to the Japan Times, Ituro Inoue and colleagues believe the virus gained a mutation in its error-correcting protein, allowing for genetic errors to accumulate to such a degree that it could no longer replicate.
While it would likely not be the first time a virus has "self-destructed" under the weight of its own rapid evolution, it is a phenomenon poorly-documented and a lucky escape for the nation.
“We were literally shocked to see the findings,” Inoue told The Japan Times in an interview.
“The delta variant in Japan was highly transmissible and keeping other variants out. But as the mutations piled up, we believe it eventually became a faulty virus and it was unable to make copies of itself. Considering that the cases haven’t been increasing, we think that at some point during such mutations it headed straight toward its natural extinction.”
The idea began when the researchers delved into the genomic profiles of the Delta variant and compared them to the Alpha variants. The expectation was that the Delta variant would be extremely diverse, with multiple lines branching out from the original strain. Instead, they discovered the Delta variant actually had just two major groups, before it seemed to abruptly halt. The Delta variant, at least in Japan, was no longer mutating and diverging into sublineages.
Looking deeper, the researchers examined the viral protein nsp14. This protein has been previously shown to be a proofreading enzyme in RNA viruses – that is to say every time the genetic code of the virus replicates, nsp14 scans through the newly-created genetic material to make sure no errors have cropped up. Mutations in proofreading enzymes spell disaster for organisms that don’t replicate often, so in a virus (which enters the cell, replicates into thousands of virions, and bursts from the host cell in around 10 hours), a faulty enzyme would spell utter catastrophe.
They found multiple genetic changes at a site within nsp14, called A394V. These mutations appear to contribute to a crippled virus that is unable to replicate, which could explain how the Delta variant simply vanished from Japan in a matter of months.
The theory is certainly interesting but doesn’t quite explain why the crippled virus would outcompete the dominant strain. There are of course other explanations – Japan has one of the highest vaccination rates and people are extremely disciplined at wearing masks, meaning outbreaks in populated areas are likely to be quashed fast. However, it certainly highlights a possible reason behind the decline in cases, and even suggests a possible therapeutic against RNA viruses.