Lab experiments have identified a mutation that would make the mosquito-borne Zika virus more infectious and virulent, a finding that will inform genomic surveillance
A single mutation could make the mosquito-borne Zika virus a lot more infectious and dangerous.
Zika typically causes few symptoms, if any, in adults, but if infection occurs during pregnancy it can cause microcephaly, a condition in which babies are born with a small head and sometimes brain damage. An outbreak in late 2015 led to the virus being linked to microcephaly in over 30 countries.
Sujan Shresta at La Jolla Institute for Immunology in California and her colleagues wanted to mimic the infection cycle of the virus to see how it could mutate in the future. To do this, they repeatedly switched the virus back and forth between mosquito and mouse cells.
The researchers also wanted to see if the virus evolved differently in mice that had been previously exposed to dengue virus, which causes dengue fever.
Zika virus is more common in countries where dengue virus is also prevalent, says Shresta. This is probably because both viruses are spread by the same types of mosquitoes and both are part of the flavivirus family. “People who have been exposed to dengue fever have short-term protection against Zika,” says Shresta.
The researchers found that the same mutant form of the Zika virus developed in mouse cells that had been exposed to dengue virus and those that hadn’t. The fact it happened in both groups suggests this part of the virus’s genome is a mutation hotspot, says Shresta.
The team then infected several pregnant mice with the mutant virus, and found that it was more infectious and more virulent. This means that the virus has a greater chance of crossing the placenta and infecting fetuses, says Shresta.
The team also infected human fetal cells in the lab, and found that the mutant virus could replicate more easily than the original virus. The researchers are now trying to figure out how exactly this mutation is making the virus more infectious.
There is no guarantee that the mutant virus will also arise in the real world, but by identifying what potential mutants may look like, we can take quicker action if they do appear, says Shresta. “We need to increase scientific capabilities in different parts of the world and monitor the emergence of these variants,” she says.
“Zika virus remains a complicated disease to study as its presence is often hidden,” says Henrik Salje at the University of Cambridge. “Most infections go undetected or are misdiagnosed due to the similarity of symptoms with other diseases. We therefore only have a limited understanding of the underlying viral diversity of circulating strains.
“Studies such as this one help to identify changes in the virus that could lead to increased virulence and will help guide genomic surveillance efforts,” says Salje.
Journal reference: Cell Reports, DOI: 10.1016/j.celrep.2022.110655
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