image: Three-dimensional structure of Zika envelope and membrane proteins. The critical mutation V473M in the envelope protein is located at the transmembrane region (indicated by an arrow). view more
Credit: The University of Texas Medical Branch at Galveston
GALVESTON, Texas - A multidisciplinary team from The University of Texas Medical Branch at Galveston has uncovered a Zika virus mutation that may be responsible for the explosive viral transmission in 2015/2016 and for the cause of microcephaly (babies with small heads) born to infected pregnant women. The study is currently available in Proceedings of National Academy of Sciences.
The Zika virus caused a global epidemic in 2015 and 2016. Like West Nile, dengue, yellow fever, and chikungunya viruses, the Zika virus is primarily transmitted by mosquitoes. These viruses pose constant threats to populations living in areas with mosquitoes. Dengue virus alone causes 390 million human infections each year. Because these viruses circulate between mosquitoes and animals/humans, they are prone to genetic mutations, making them highly capable of emerging and causing epidemics.
In this study, the UTMB team has identified a mutation in the Zika envelope protein that can enhance mother-to-baby transmission in pregnant mice, increase neurological disease and lethality in newborn mice and elevate virus levels in the blood of infected non-human primates. When a mosquito bites an individual with the Zika virus, the elevated virus level in the blood increases the potential of transmitting the virus to mosquitoes, consequently promoting the establishment of urban transmission of the virus between mosquitoes and humans.
"Our study demonstrates that the Zika envelope mutation V473M, which just occurred before the 2015 epidemic in the Americas, enhances Zika virus particle assembly in infected cells. The enhanced virus assembly leads to increased human disease and maternal transmission," said Pei-Yong Shi, I.H. Kempner professor of Human Genetics at UTMB. "The viral genetic change reported here, combined with the naïve herd immunity, may have accounted for the Zika epidemic and severe diseases in 2015 and 2016."
"There are over 500 known arboviruses, among which 100 of these can cause human diseases," said Chao Shan, a former UTMB Research Scientist who co-senior authored the study. "Because arbovirus polymerase - an enzyme responsible for amplifying the viral genetic footprint - lacks proofreading capability, these viruses are prone to high mutation frequencies. So, these viruses often emerge and reemerge. During the past two decades, we have witnessed the emergence of West Nile, dengue, yellow fever, chikungunya viruses, and Zika viruses."
"RNA viruses are the pathogens most often responsible for outbreaks and epidemics, including Ebola virus and SARS-CoV-2, the virus causing COVID-19" said Shi. "Understanding the mechanisms of viral emergence and transmission is essential to detect and respond to future outbreaks. Although the world is currently focusing on COVID-19, I am certain that COVID-19 will not be the last emerging virus we face. Moving forward, building public health capacity and countermeasure technology are the only effective means to overcome these threats."
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Other UTMB authors and external collaborators include Hongjie Xia, Sherry Haller, Sasha Azar, Yang Liu, Jianying Liu, Antonio Muruato, Rubing Chen, Shannan Ross, Maki Wakamiya, Nikos Vasilakis, Rongjuan Pei, Camila Fontes-Garfias, Sanjay Kumar Singh, Xuping Xie and Scott Weaver.
To study emerging viruses, the UTMB team has received grants from the National Institutes of Health and philanthropic support from the Sealy & Smith Foundation; Robert J. Kleberg, Jr. and Helen C. Kleberg Foundation; John S. Dunn Foundation; Amon G. Carter Foundation; Gillson Longenbaugh Foundation; Summerfield G. Roberts Foundation.
Journal
Proceedings of the National Academy of Sciences