Science & Technology

A Small Mutation Can Make Zika Virus Even Extra Harmful – And Potentially Breakthrough Pre-Present Immunity


Zika Malaria Mosquito Virus Concept Illustration

How Zika outbreaks might occur, even in areas with prior immunity.

Researchers at La Jolla Institute for Immunology (LJI) have found that the Zika virus can mutate to grow to be extra infectious—and doubtlessly breakthrough pre-existing immunity.

“The world should monitor the emergence of this Zika virus variant,” says LJI Professor Sujan Shresta, Ph.D., who co-led the Cell Reports examine with Professor Pei-Yong Shi, Ph.D., of the University of Texas Medical Branch (UTMB).

Microcephaly is a beginning defect the place a child’s head is smaller than anticipated compared to different infants of the identical intercourse and age. Babies with microcephaly regularly have smaller brains which may not have developed correctly.

Zika virus is unfold by mosquitoes, and the signs of Zika an infection in adults are normally delicate. However, the virus can infect a creating fetus, leading to main beginning defects akin to microcephaly.

Zika virus and dengue virus overlap in lots of international locations worldwide. Like Zika, the dengue virus is a mosquito-borne flavivirus, and thus shares many organic properties. In truth, the viruses are related sufficient that the immune response sparked by prior dengue publicity can provide safety in opposition to 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,” says Shresta.

Unfortunately, each viruses are additionally fast to mutate. “Dengue and Zika are RNA viruses, which means they can change their genome,” explains Shresta. “When there are so many mosquitoes and so many human hosts, these viruses are constantly moving back and forth and evolving.”

Zika Infection Cycle

Repeatedly switching forwards and backwards between mosquito cells and mice supplied scientists with a window into how Zika virus naturally evolves because it encounters extra hosts. Credit: La Jolla Institute for Immunology. Credit: La Jolla Institute for Immunology

To examine Zika’s fast-paced evolution, the LJI workforce recreated an infection cycles that repeatedly switched forwards and backwards between mosquito cells and mice. This work gave the LJI scientists a window into how Zika virus naturally evolves because it encounters extra hosts.

The researchers discovered it’s comparatively straightforward for Zika virus to amass a single amino acid change that enables the virus to make extra copies of itself—and assist infections take maintain extra simply. This mutation (referred to as NS2B I39V/I39T mutation) boosts the virus’s potential to copy in each mice and mosquitoes. This Zika variant additionally confirmed elevated replication in human cells.

“This single mutation is sufficient to enhance Zika virus virulence,” says examine first writer Jose Angel Regla-Nava, Ph.D., former postdoctoral researcher at LJI and present Associate Professor on the University of Guadalajara, Mexico. “A high replication rate in either a  mosquito or human host could increase viral transmission or pathogenicity—and cause a new outbreak.”

Adds Shresta, “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.”

So how can we put together for this type of variant? Shresta’s laboratory is already taking a look at methods to tailor Zika vaccines and coverings that counteract this harmful mutation. She may also proceed to work carefully with Regla-Nava to raised perceive precisely how this mutation helps Zika replicate extra effectively.

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

Reference: “A Zika virus mutation enhances transmission potential and confers escape from protective dengue virus immunity” by Jose Angel Regla-Nava, Ying-Ting Wang, Camila R. Fontes-Garfias, Yang Liu, Thasneem Syed, Mercylia Susantono, Andrew Gonzalez, Karla M. Viramontes, Shailendra Kumar Verma, Kenneth Kim, Sara Landeras-Bueno, Chun-Teng Huang, Daniil M. Prigozhin, Joseph G. Gleeson, Alexey V. Terskikh, Pei-Yong Shi and Sujan Shresta, 12 April 2022, Cell Reports.
DOI: 10.1016/j.celrep.2022.110655

Additional authors of the examine, “A Zika Virus Mutation Enhances Transmission Potential and Confers Escape from Protective Dengue Virus Immunity,” embody first writer Jose Angel Regla-Nava, Ying-Ting Wang, Camila R Fontes-Garfias, Yang Liu, Thasneem Syed, Mercylia Susantono, Andrew Gonzalez, Karla Viramontes, Shailendra Verma, Kenneth Kim, Sara Landeras-Bueno, Chun-Teng Huang, Daniil M Prigozhin, Joseph G Gleeson, and Alexey V Terskikh.

This analysis was supported by the the National Institutes of Health (R01 AI153500, R01 AI163188, R56 AI148635, U01 AI151810, R01 NS106387, R01 AI134907, R43 AI145617, and UL1 TR001439), the Sealy & Smith Foundation, the Kleberg Foundation, the John S. Dunn Foundation, the Amon G. Carter Foundation, the Gilson Longenbaugh Foundation, and the Summerfield Robert Foundation.





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