Back in January 2020, I wrote about a deletion that appeared in the genome of SARS-CoV during the middle and late phase of the epidemic (link to article). A similar deletion has now been detected in the genome of SARS-CoV-2 (link to article).
The deletion in the SARS-CoV genome occurred in a region encoding a protein called Orf8. It was initially suggested that the 29 nucleotide deletion was somehow involved in adaptation of SARS-CoV to humans. This hypothesis was disproven in subsequent experiments which demonstrated that the 29 nucleotide deletion decreases viral replication in a number of different cell types. In other words, this virus has reduced fitness compared with a virus containing a full Orf8.
SARS-CoV-2 viruses with a 382 nucleotide deletion, which encompasses almost the entire open reading frame of Orf8, have now been isolated from eight hospitalized patients in Singapore (image below). These viruses appear to have been circulating in Singapore for at least four weeks.
The authors of the study suggest that the deletion might lead to reduced virulence of SARS-CoV-2. This hypothesis is based on the reduced fitness of SARS-CoV lacking Orf8 in cell culture. In the article that I published here on 23 January 2020, I wrote “The genome sequence of 2019-CoV (the name at the time for SARS-CoV-2) shows that Orf8 is intact. If it is not lost during subsequent virus circulation in humans, the outbreak could be more severe.”
So far the pandemic caused by SARS-CoV-2 has been quite severe with a crude fatality rate globally of ~6%. Whether or not the Orf8 deletion will reduce virulence of the virus in humans is unknown. By analogy with SARS-CoV, the Orf8 deletion likely reduces the fitness of SARS-CoV-2 and therefore the mutant virus might not be able to compete with viruses with the intact gene.
Orf8 deleted SARS-CoV-2 viruses have not yet been reported outside of Singapore. It will be important to look carefully at this region of the genome in future virus isolates to determine if this altered virus is capable of global spread, and if so, whether it is accompanied by reduced virulence.