Breaking News
February 17, 2019 - Support from trusted adults can reduce risk of dying in suicidal teens, finds study
February 17, 2019 - Heart attack awareness improved since 2008
February 17, 2019 - Exercise gives a better brain boost to older men than women
February 17, 2019 - New research disproves previous assumptions of how looks influence personality
February 17, 2019 - Cannabis use as a teenager linked to depression later in life
February 17, 2019 - Sinks by Toilets in ICU Patient Rooms Harbor Harmful Bacteria
February 17, 2019 - Cancer cells’ plasticity makes them harder to stop
February 17, 2019 - Young cannabis users have increased risk of depression and suicidal behavior
February 17, 2019 - Tasmanian Devils Likely to Survive Cancer Scourge
February 17, 2019 - Neoadjuvant PD-1 blockade seems effective in glioblastoma
February 17, 2019 - Personal, social factors play role in enabling sustainable return to work after ill health
February 17, 2019 - Mouse studies show ‘inhibition’ theory of autism wrong
February 17, 2019 - Study shows how neuroactive steroids inhibit activity of pro-inflammatory proteins
February 17, 2019 - Use of liver grafts from older donors decreased despite better outcomes in recipients
February 17, 2019 - MUSC researchers discover new mechanism for a class of anti-cancer drugs
February 17, 2019 - HPV misconceptions are causing women to miss smear tests
February 17, 2019 - Sanofi and Regeneron Offer Praluent (alirocumab) at a New Reduced U.S. List Price
February 17, 2019 - Researchers say auditory testing can identify children for autism screening
February 17, 2019 - New method analyzes how single biological cells react to stressful situations
February 17, 2019 - WVU gynecologic oncologist investigates novel treatment for cervical and vaginal cancers
February 17, 2019 - ADHD diagnoses poorly documented
February 17, 2019 - Majority of gender minority youth do not identify with traditional sexual identity labels
February 17, 2019 - AbbVie, Teneobio enter into strategic transaction to develop potential treatment for multiple myeloma
February 17, 2019 - Lower Birth Weight May Up Risk for Psychiatric Disorders
February 17, 2019 - Scientists identify reversible molecular defect underlying rheumatoid arthritis
February 17, 2019 - Moffitt researchers shed light on how CAR T cells function mechanistically
February 16, 2019 - Female Anatomy May Play Big Role in Sperm’s Success
February 16, 2019 - BMI may mediate inverse link between fiber intake, knee OA
February 16, 2019 - Movement impairments in autism can be reversed through behavioral training
February 16, 2019 - Studies address racial disparities in postpartum period and cardiovascular health
February 16, 2019 - Scientists implicate hidden genes in the severity of autism symptoms
February 16, 2019 - Decreased deep sleep linked to early signs of Alzheimer’s disease
February 16, 2019 - Neuroscientists show how the brain responds to texture
February 16, 2019 - Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
February 16, 2019 - What Can I Do About Sweating? (for Teens)
February 16, 2019 - Companies navigate dementia conversations with older workers
February 16, 2019 - Newly developed stem cell technologies show promise for treating PD patients
February 16, 2019 - Collaborative material research could advance self-assembling nanomaterials
February 16, 2019 - Researchers take major step in creating technology that mimics the human brain
February 16, 2019 - Erasing memories associated with cocaine use reduces drug seeking behavior
February 16, 2019 - Artificial intelligence can accurately predict prognosis of ovarian cancer patients
February 16, 2019 - Racial disparities in cancer deaths on the decline for America
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Children with ASD more likely to face maltreatment, study finds
February 16, 2019 - Study finds genetic vulnerability to use of menthol cigarettes
February 16, 2019 - Promising drug developed to rejuvenate muscle cells
February 16, 2019 - H-RT should be the standard of care for men with low risk prostate cancer, study shows
February 16, 2019 - New technique using patients’ own modified cells could help treat Crohn’s disease
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
Researchers use CRISPR to identify gene that helps cells resist flavivirus infection

Researchers use CRISPR to identify gene that helps cells resist flavivirus infection

image_pdfDownload PDFimage_print

UT Southwestern researchers today report the first use of CRISPR genome-wide screening to identify a gene that helps cells resist flavivirus infection. That nasty class of pathogens includes West Nile virus, dengue fever, Zika virus, and yellow fever.

In a study published in Nature Microbiology, the team led by Dr. John Schoggins, Assistant Professor of Microbiology, used the cutting-edge CRISPR technology to identify the IFI6 gene as a potent antiviral gene targeting flaviviruses. The researchers then used traditional cell culture studies to confirm the gene’s role in protecting against infection by Zika, West Nile, dengue, and yellow fever viruses.

“Other studies have used CRISPR genetic screens to identify cellular genes that are required for flavivirus infection. Our study is the first to use this technology to identify cellular genes that inhibit infection,” said Dr. Schoggins, a Nancy Cain and Jeffrey A. Marcus Scholar in Medical Research, in Honor of Dr. Bill S. Vowell, and a Clayton Foundation Investigator.

“In mammals, cells naturally defend against viral infection through interferon, a molecule that sets off a warning system that a virus has been detected and that the cells need to engage their viral defense systems. The cells do this by activating hundreds of interferon-stimulated genes,” he said. “Flaviviruses cause substantial human disease, and interferon is involved in the body’s innate immune response to these viruses.”

Dr. Schoggins said the team used recently developed genome-wide CRISPR screening technology to identify which of the interferon-induced genes played a major role in suppressing flavivirus infection. He praised the work of graduate student and lead author Blake Richardson and of co-author Dr. Maikke Ohlson, a senior research scientist in his laboratory. “Blake performed all the phenotypic and mechanistic work on how IFI6 inhibits flaviviruses and Dr. Ohlson performed the CRISPR screen that allowed us to uncover IFI6 as a potent suppressor of flavivirus infection,” he said.

“In the CRISPR screen, we used human liver cells and knocked out every gene in the genome – about 19,000 genes – one at a time. We then stimulated the cells with interferon, knowing that this stimulation would normally allow the cells to resist viral infection. For the cells that did not resist infection – because they were missing a gene due to the CRISPR knockout – we used next-generation sequencing to figure out the identity of the relevant genes,” he said.

Dr. Schoggins explained that the CRISPR gene-editing technology made such a study extremely efficient, uncovering the prominent flavivirus-inhibiting role of IFI6.

“The brilliance of the technology is that all of these CRISPR-targeted cells are pooled together in just a few big cell culture dishes. The cells are also bar-coded so you know which gene is missing from each cell when you observe how they respond to the addition of interferon,” he said.

“The technology is super cool,” he added.

In cell culture studies, the IFI6 gene – apparently working via its protein product, also called IFI6 – inhibited yellow fever, a flavivirus known to infect the liver. Cells with a working IFI6 gene also inhibited dengue, Zika, and West Nile viruses, he said. The researchers confirmed those results in liver cells by repeating the experiment in kidney and skin cell lines and in neurons.

Future work will entail drilling down into the molecular mechanism of the IFI6 protein, with the hope that this knowledge may provide a foundation for developing therapies that could target flavivirus infection.

Sporadic West Nile cases have been reported this summer in the United States, he said, adding, “Zika has waned, but I think people still remember it quite well; dengue is an ongoing problem in tropical climates, and there’s currently an outbreak of yellow fever virus in Brazil.”

In earlier studies, Dr. Schoggins and other researchers identified other possible flavivirus resistance proteins using non-CRISPR screening techniques, but the CRISPR technology makes IFI6 appear to play a more prominent role, he said.

Questions still to be answered include whether CRISPR screens in other cell types would give different results. This study focused on liver cells because it began as an investigation of yellow fever, which is known to attack the liver. Zika is known to affect cells in the brain but CRISPR genetic screening in neurons presents logistical challenges, he explained.

Source:

https://www.utsouthwestern.edu/newsroom/articles/year-2018/crispr-west-nile-zika.html

Tagged with:

About author

Related Articles