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

Date:
August 12, 2020
Source:
University of California - Riverside
Summary:
A research team has outlined how the Zika virus, which constituted
an epidemic threat in 2016, suppresses the immune system of
its host. The 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.



FULL STORY ==========================================================================
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.

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.


========================================================================== Story Source: Materials provided by
University_of_California_-_Riverside. Original written by Iqbal
Pittalwala. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Boxiao Wang, Stephanie Thurmond, Kang Zhou, Maria
T. Sa'nchez-Aparicio,
Jian Fang, Jiuwei Lu, Linfeng Gao, Wendan Ren, Yanxiang Cui,
Ethan C.

Veit, HeaJin Hong, Matthew J. Evans, Sea'n E. O'Leary, Adolfo
Garci'a- Sastre, Z. Hong Zhou, Rong Hai, Jikui Song. Structural
basis for STAT2 suppression by flavivirus NS5. Nature Structural &
Molecular Biology, 2020; DOI: 10.1038/s41594-020-0472-y ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200812153632.htm

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