skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Validation of Novel and Known Host Factors in CRISPR Genome-wide Screening for Zika Virus.

Abstract

Abstract not provided.

Authors:
; ; ;
Publication Date:
Research Org.:
Sandia National Lab. (SNL-CA), Livermore, CA (United States)
Sponsoring Org.:
USDOE National Nuclear Security Administration (NNSA)
OSTI Identifier:
1373052
Report Number(s):
SAND2016-6993D
645962
DOE Contract Number:
AC04-94AL85000
Resource Type:
Conference
Resource Relation:
Conference: Proposed for presentation at the Symposium.
Country of Publication:
United States
Language:
English

Citation Formats

Techel, Jessica, Grant, Christopher, Bird, Sara, and Negrete, Oscar. Validation of Novel and Known Host Factors in CRISPR Genome-wide Screening for Zika Virus.. United States: N. p., 2016. Web.
Techel, Jessica, Grant, Christopher, Bird, Sara, & Negrete, Oscar. Validation of Novel and Known Host Factors in CRISPR Genome-wide Screening for Zika Virus.. United States.
Techel, Jessica, Grant, Christopher, Bird, Sara, and Negrete, Oscar. Fri . "Validation of Novel and Known Host Factors in CRISPR Genome-wide Screening for Zika Virus.". United States. doi:. https://www.osti.gov/servlets/purl/1373052.
@article{osti_1373052,
title = {Validation of Novel and Known Host Factors in CRISPR Genome-wide Screening for Zika Virus.},
author = {Techel, Jessica and Grant, Christopher and Bird, Sara and Negrete, Oscar},
abstractNote = {Abstract not provided.},
doi = {},
journal = {},
number = ,
volume = ,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2016},
month = {Fri Jul 01 00:00:00 EDT 2016}
}

Conference:
Other availability
Please see Document Availability for additional information on obtaining the full-text document. Library patrons may search WorldCat to identify libraries that hold this conference proceeding.

Save / Share:
  • Abstract not provided.
  • Abstract not provided.
  • Abstract not provided.
  • We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retardingmore » ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. - Highlights: •Hemin treatment protected monocyte-derived macrophages against Zika virus (ZIKV) infection. •Innate cellular protection against ZIKV infection correlated with Nrf2-dependent HO-1 expression. •Stimulation of innate cellular responses may provide a therapeutic strategy against ZIKV infection.« less
  • Zika flavivirus infection during pregnancy appears to produce higher risk of microcephaly, and also causes multiple neurological problems such as Guillain–Barré syndrome. The Zika virus is now widespread in Central and South America, and is anticipated to become an increasing risk in the southern United States. With continuing global travel and the spread of the mosquito vector, the exposure is expected to accelerate, but there are no currently approved treatments against the Zika virus. The Zika NS2B/NS3 protease is an attractive drug target due to its essential role in viral replication. Our studies have identified several compounds with inhibitory activitymore » (IC50) and binding affinity (KD) of ~5–10 μM against the Zika NS2B-NS3 protease from testing 71 HCV NS3/NS4A inhibitors that were initially discovered by high-throughput screening of 40,967 compounds. Competition surface plasmon resonance studies and mechanism of inhibition analyses by enzyme kinetics subsequently determined the best compound to be a competitive inhibitor with a Ki value of 9.5 μM. We also determined the X-ray structure of the Zika NS2B-NS3 protease in a “pre-open conformation”, a conformation never observed before for any flavivirus proteases. This provides the foundation for new structure-based inhibitor design.« less