Single mutation turned Zika from irritant to horror

The Zika virus, declared in February 2016 by the World Health Organisation to be a Public Health Emergency of International Concern, made the jump from irritant to serious problem as a result of a single DNA mutation which caused it to induce microcephaly – an abnormally small head — in human foetuses, research has found.

In a paper in the journal Science researchers conclude that the mutation emerged at some time in May 2013, a few months ahead of a Zika outbreak in French Polynesia.

The study, led by Ling Yuan of the Chinese Academy of Sciences in Beijing, uncovers the mechanism by which Zika changed from a mostly harmless mosquito-borne virus into a serious pathogen capable of causing devastating birth defects. 

The virus was first isolated from a sentinel monkey in the Zika forests of Uganda in 1947. It was considered a mild disease, similar to dengue fever.

After several “explosive” outbreaks, in 2007 in Micronesia, and 2013-14 in French Polynesia, Zika swept through South and Central America in 2015, prompting the WHO declaration, “owing to its unexpected causal link to congenital brain abnormalities, especially microcephaly during pregnancy”.

The researchers identified a single amino acid substitution on a DNA strand that boosted the virulence of the virus when it was introduced into human and mouse cell lines in the laboratory. Viruses carrying the changed amino acid also correlated with microcephaly cases in mice foetuses. 

Zika can be divided into African and Asian lineages, the researchers say. The strains that affected Pacific islands and the Americas are “likely to have evolved from a common ancestral strain in south-east Asia”.

However, there is evidence that this ancestral strain had been circulating in the region for many years, without being linked to birth defects.

After investigating three contemporary Zika strains and comparing them to the originating Asian strain (which was isolated in Cambodia in 2010), they found the contemporary strains caused far more brain damage than did their ancestor. Genome sequencing revealed several substitutions of amino acids that arose before the South American outbreaks and were maintained in contemporary epidemic strains.

They eventually narrowed their search down to one specific mutation strain, potentially providing a vaccine target.

However, Yuan and his colleagues warn that Zika may not yet have revealed all its secrets. The paper notes that studies have identified other amino acid substitutions in some virus populations that appear to increase its ability to infect new hosts.

The scientists urge more research into “the potential relationship between epidemic potential and disease severity”.