Study provides insights into how Zika virus suppresses the host immune system

Anonymous — Thu, 03 Sep 2020 17:34:54 +0000

Study provides insights into how Zika virus suppresses the host immune system Anonymous (not verified) Thu, 09/03/2020 - 10:34 More News Iqbal Pittalwala August 12, 2020

A research team led by scientists at the University of California, Riverside, has outlined how the Zika virus, which constituted an epidemic threat in 2016, suppresses the immune system of its host.

The Zika virus, or ZIKV, spreads through mosquito bites and sexual intercourse. Currently, no approved vaccine or antivirals against ZIKV exist.

“Suppressing host immunity is a common strategy employed by viruses to achieve successful infection,” said Jikui Song, a professor of biochemistry at UCR, who co-led the study. “Our work provides valuable structural and functional information on the interaction between ZIKV and its host and offers a framework for the development of vaccines and antivirals.”

The study appears in Nature Structural & Molecular Biology.

Jikui Song (left) and Rong Hai. (UCR/Song lab)

Song explained the steps involved in suppressing the host immune response. ZIKV encounters the first line of defense by way of a type I interferon, or IFN, response in the host. Secreted by infected cells, IFNs are natural substances that help the host’s immune system fight infection. Once ZIKV infects the cell, it presents a nonstructural protein, NS5, which interacts with a key player in the type I IFN pathway: the STAT2 protein. The interaction between ZIKV NS5 and STAT2 degrades STAT2, which inhibits the type I IFN response.

The research involved first solving the crystal structure of a complex between a large fragment of ZIKV NS5 and STAT2. This crystal structure guided the researchers in solving the cryo-EM structure of ZIKV NS5 and STAT2, which then led them to come up with a model for how ZIKV NS5 suppresses human STAT2.

“Understanding the interaction, at the molecular level, between ZIKV NS5 and the host immune factor STAT2, opens up a new window for the rational design of live attenuated vaccines and antivirals” said study co-leader Rong Hai, an assistant professor of virology at UCR. “Targeting the virus-host interaction may also provide an important approach for drug development against SARS-CoV-2, the virus that causes COVID-19.”

The researchers also generated a panel of mutant ZIKV viruses.

“To our knowledge, these are the first NS5-based ZIKV mutants, which have the potential to be used as live attenuated ZIKV vaccines,” Hai said.

Next, the researchers will work on the structure and function of SARS-CoV-2 proteins to identify new targets against COVID-19.

Song and Hai were joined in the study by Z. Hong Zhou at UCLA, also a senior author of the research paper. Other coauthors include UCR’s Boxiao Wang and Stephanie Thurmond. Kang Zhou at UCLA and Maria T. Sánchez-Aparicio at the Icahn School of Medicine at Mount Sinai share co-first authorship with Wang and Thurmond.

Song was supported by a grant from the National Institutes of Health, or NIH, and a University of California Cancer Research Coordinating Committee Faculty Seed Grant. A second NIH grant funded both Song and Hai.

The research paper is titled “Structural basis for STAT2 suppression by flavivirus NS5.”

Header image credit: Manuel Almagro Rivas on Wikimedia Commons.

Scientists Decode DNA Secrets of World's Toughest Bean

Anonymous — Tue, 21 Jan 2020 18:18:38 +0000

Scientists Decode DNA Secrets of World's Toughest Bean Anonymous (not verified) Tue, 01/21/2020 - 10:18 More News January 21, 2020

UC Riverside scientists have decoded the genome of black-eyed peas, offering hope for feeding Earth’s expanding population, especially as the climate changes.

Understanding the genes responsible for the peas’ drought and heat tolerance eventually could help make other crops tougher too. Black-eyed peas are small beans with dark midsections. They’ve been a global dietary staple for centuries due to their environmental toughness and exceptional nutritional qualities, such as high protein and low fat. In sub-Saharan Africa they remain the number one source of protein in the human diet.

A genome is the full collection of genetic codes that determine characteristics like color, height, and predisposition to diseases. All genomes contain highly repetitive sequences of DNA that UCR Professor of Computer Science and project co-leader Stefano Lonardi likens to “hundreds of thousands of identical jigsaw puzzle pieces.”

Lonardi described the process of figuring out how the jigsaw puzzle sequences fit together as “computationally challenging.” In order to do so, Lonardi’s team assembled the genome many times with different software tools and parameters. Then they created new software capable of merging these various genome solutions into a single, complete picture.

With the success of this project, the black-eyed pea joins only a handful of other major crops whose genomes have been fully sequenced. The team’s work on the project was published in the June issue of The Plant Journal, where it was featured as the cover story, and Lonardi’s free software can be downloaded online.

Research on black-eyed peas, a legume also known as cowpea, started at UC Riverside more than 40 years ago. But cowpeas’ presence in Riverside predates the university by about 200 years.

“The cowpea has been here supporting people since early colonial times,” said project co-leader Timothy Close, a UCR professor of botany and plant sciences. ‘It’s nice that we’ve brought this plant with so much local history up to state of the art for scientific research.”

This is the first high-quality reference genome for the cowpea. Work on it began three years ago, made possible mainly by a $1.6 million grant from the National Science Foundation, or NSF. An additional $500,000 NSF grant also supported the computational efforts.

A clue to the complexity of the project is the size of the research team. In addition to Close and Lonardi, the many other UCR scientists on the team included María Muñoz-Amatrían, Qihua Liang, Steve Wanamaker, Sassoum Lo, Hind Alhakami, Rachid Ounit, Philip Roberts, Jansen Santos, Arsenio Ndeve, and Abid Md. Hasan. Additional team members inside the U.S. came from UC Davis, the Department of Energy’s Joint Genome Institute in California, the National Center for Genome Resources in New Mexico, and the U.S. Department of Agriculture in Iowa. International team members came from Finland, France, Brazil, and the Czech Republic.

As with humans, there are differences between individual cowpeas. Knowing which genes are responsible for qualities in individuals such as color, size, or pathogen resistance will help breeders develop new varieties even better able to withstand external challenges.

“Having the genome sequence helps scientists make decisions about the choice of parent plants to crossbreed in order to produce their desired progeny,” Close said.

One of the cowpea traits that scientists are now trying to understand is its remarkable ability to recover from drought stress.

“We’re trying to figure out why cowpeas are so resilient to harsh conditions,” said Close. “As we move into a world with less water available to agriculture, it will be important to capitalize on this ability and expand on it, taking the lead from cowpeas to guide improvements in other crops that are vulnerable to climate change.”