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The world must guard against the Zika virus

T + T – normal size

Researchers at the La Jolla Institute of Immunology have found that the mosquito-borne Zika virus can mutate to become more contagious, potentially eliminating previously acquired immunity.

“The world should be watching for the emergence of the Zika virus variant,” said Professor Sujan Shrestha, a professor at the La Jolla Institute of Immunology in California, who co-led the study published in Cell Reports with Professor Bai Yong Shi of the University of Texas Medical Branch (UTMB). .

Zika virus is transmitted by mosquitoes, and symptoms of Zika infection are usually mild in adults. However, the virus can infect a developing fetus, leading to birth defects, such as microcephaly.

Zika virus and dengue virus overlap in many countries around the world. Dengue virus, like Zika virus, is a mosquito-borne flavivirus, and thus shares many biological characteristics.

In fact, Zika and dengue are two viruses similar enough that a person previously exposed to dengue becomes immune to Zika thanks to the interaction of T cells and antibodies.

“In areas where Zika is common, the vast majority of people have already been exposed to the dengue virus and have both T cells and antibodies that react,” Shrestha explains.

Unfortunately, both viruses mutate rapidly as well. “Dengue and Zika are RNA viruses, which means they are able to alter their genomes. And when there are a lot of mosquitoes and many human hosts, these viruses are constantly moving back and forth and evolving,” Shrestha explains.

To study the rapid evolution of the Zika virus, the La Jolla Institute of Immunology team re-established cycles of infection that repeatedly moved back and forth between the cells of mosquitoes and mice.

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This work gave researchers at the La Jolla Institute of Immunology a window into how the Zika virus naturally evolved as it encounters more hosts.

The team found that it is relatively easy for the Zika virus to acquire a single amino acid change that allows the virus to make more copies of itself – and helps the infection to control more easily.

This mutation (called the NS2B I39V/I39T mutation) enhances the virus’s ability to replicate in both mice and mosquitoes. This Zika variant also showed increased proliferation in human cells.

Study first author Dr. José Angel Regla Nava, a former postdoctoral researcher at the La Jolla Institute of Immunology and currently Associate Professor at the University of Guadalajara in Mexico, says:

“This single mutation is sufficient to enhance the virulence of Zika virus. A high reproductive rate in mosquitoes or the human host could increase virus transmission or pathogenicity, and cause new outbreaks.”

“The Zika variant we identified has evolved to the point where the protective immunity provided by previous dengue infection is no longer effective in mice. Unfortunately, if this variant becomes dominant, we may face the same problems in real life,” Shrestha adds.

So how do we prepare for these kind of variables?

To deal with the new mutation of the Zika virus, Shrestha’s lab is already looking at ways to design Zika vaccines and treatments to counter this dangerous mutation, as well as working to determine how exactly changing the genome helps the pathogen reproduce faster.

She will also continue to work closely with Dr. Regla Nava to better understand how this mutation can help Zika reproduce more efficiently.

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“We want to understand at what point in the viral life cycle this mutation makes a difference,” Shrestha explains.

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