How Do Zika Viruses Assemble During an Infection

A viral protein called NS2A orchestrates the Zika virus assembly by protease
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(Zika News)

A new study published by the University of Texas Medical Branch (UTMB) at Galveston has unraveled the mystery of how the Zika virus assembles when they infect human and mosquito hosts.

Prior to this study published in mBio on October 29, 2019, ‘it was not well understood how the viral structural proteins and genome are assembled into virus particles within infected cells,’ said these researchers.

This is important since the Zika virus can cause devastating congenital Zika syndromes in pregnant women and Guillain-Barre syndrome in adults.

The UTMB researchers reported that ‘the Zika virus NS2A plays a central role in recruiting viral RNA, structural protein prM/E, and viral NS2B/NS3 protease to the virion assembly site and orchestrating virion morphogenesis.’

‘This knowledge can now be used to deter or stop the viruses from gaining full strength through inhibiting virus formation.’

“Using biochemical, microscopic imaging and virological methods, we demonstrated that a viral protein called NS2A orchestrates the virus assembly by recruiting the structural proteins, viral genome and viral enzyme called protease to the assembly site,” said Xuping Xie, Ph.D., a UTMB research scientist who co-directed the study, in a November 13, 2019, press release.

“At the assembly site, the viral protease cuts down a structural protein pre-cursor into mature proteins that bind to the viral genome to form a new virus. So, the assembly of these viruses is closely regulated by the viral protease.”

“Virus assembly is an understudied research topic,” says Mariano Garcia-Blanco, M.D., Ph.D., Professor at UTMB, who is not directly involved in the study. “Once the assembly mechanism has been defined, one could design inhibitors to block virus assembly for antiviral development and to rationally engineer virus for vaccine development.”

“It is remarkable to see that the results from dengue and Zika viruses share a common assembly mechanism,” concluded Dr. Garcia-Blanco.

This study’s results are important since closely related flaviviruses cause frequent epidemics around the world, including West Nile, Yellow Fever, and Dengue viruses. These viruses share a common structure containing 180 copies of structural proteins on the virus surface and an interior viral genome. 

“These findings provide new opportunities for antiviral and vaccine development,” said Pei-Yong Shi, Ph.D., UTMB professor in the department of biochemistry & molecular biology.

This study was supported by NIH grants AI142759, AI127744, and AI136126 and awards from the Kleberg Foundation, John S. Dunn Foundation, Amon G. Carter Foundation, Gilson Longenbaugh Foundation, and Summerfield Robert Foundation. No conflicts of interest were disclosed.

Zika Virus news published by Zika News.

Photo thanks to Richard Clyborne of Music Strive