HIV-protective mutation may boost influenza risk

The controversial birth of the world’s first gene-edited babies continues to make news and inspire follow-up work.

In a new study, US and Danish researchers show that the gene mutation Chinese scientist Jiankui He artificially created to try to prevent twin girls contracting their father’s HIV may actually increase their chances of dying prematurely.

Xinzhu Wei, from the University of California, Berkeley, US, and Rasmus Nielsen, from the University of Copenhagen, Denmark, analysed genotype and death register information for over 400,000 individuals in the UK Biobank and found that people with a naturally occurring mutation called Δ32 are around 20% less likely to reach age 76. 

And that, they suggest, highlights the need to better understand how the unintended consequences of introducing mutations in humans may impact health.

Their findings are published in the journal Nature Medicine. 

In November 2018, He announced that he had used CRISPR to edit the CCR5 gene in human embryos, which resulted in two live births. The introduced mutations were aimed at mimicking the effect of the naturally occurring CCR5-Δ32 mutation. 

The mutation has been shown to protect against HIV infection in Europeans, but previous studies also suggest that people who have it may be at risk for certain infectious diseases, such as influenza.

“It is perhaps not unexpected that homozygosity for a deletion in a functional gene is associated with reduced fitness,” Wei and Nielsen write. 

“It underscores the idea that introduction of new or derived mutations in humans using CRISPR technology, or other methods for genetic engineering, comes with considerable risk even if the mutations provide a perceived advantage. 

“In this case, the cost of resistance to HIV may be increased susceptibility to other, and perhaps more common, diseases.”

They note, however, that it remains to be seen if their findings can be replicated in other populations.

In January 2019, two months after the birth of He’s genetically-modified twins, Lulu and Nana, the Chinese news agency Xinhua announced that preliminary investigations had revealed that, among other things, the researcher had worked alone and forged review papers. He has not been heard from since.