Researchers have found that Zika virus has the potential to mutate and increase its infectivity, potentially breaking through pre-existing immunity.
“The world should monitor the emergence of this Zika virus variant,” said LJI Professor Sujan Shresta, PhD, who co-led the La Jolla Institute for Immunology (LJI) study which is published in Cell Reports.
A mosquito-borne virus, symptoms of Zika infection are usually mild in adults. However, in a developing foetus, infection can cause birth defects such as microcephaly.
Zika virus and dengue virus occur together in a number of countries. Both viruses are a mosquito-borne flavivirus, sharing biological similarity: similar enough that prior dengue exposure can offer immune protection against Zika.
“In areas where Zika is prevalent, a vast majority of people have already been exposed to dengue virus and have both T cells and antibodies that cross-react,” said Prof Shresta.
Unfortunately, both viruses share the trait of rapid mutation. “Dengue and Zika are RNA viruses, which means they can change their genome,” she further explained. “When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.”
To study Zika’s fast-paced evolution, the researchers simulated infection cycles that repeatedly switched back and forth between mosquito cells and mice. This painted a picture of how Zika virus naturally evolves as it encounters more hosts.
The LJI team found that an easy change of a single amino acid allows the virus to make more copies of itself — and help infections take hold more easily. This mutation (called NS2B I39V/I39T mutation) boosts viral replication in both mice and mosquitoes – and also in human cells.
“This single mutation is sufficient to enhance Zika virus virulence,” commented study first author Jose Angel Regla-Nava, PhD. “A high replication rate in either a mosquito or human host could increase viral transmission or pathogenicity – and cause a new outbreak.”
Prof Shresta added, “The Zika variant that we identified had evolved to the point where the cross-protective immunity afforded by prior dengue infection was no longer effective in mice. Unfortunately for us, if this variant becomes prevalent, we may have the same issues in real life.”
To help prepare for this variant, Dr Shresta’s laboratory is already looking at ways to tailor Zika vaccines and treatments that counteract this dangerous mutation.
“We want to understand at what point in the viral life cycle this mutation makes a difference,” said Dr Shresta.
