Breaking News
December 11, 2018 - Antioxidants may prevent cognitive impairment in diabetes
December 11, 2018 - Oral cancer prognostic signature identified
December 11, 2018 - How Can I Find Out What Caused My Miscarriage?
December 11, 2018 - Novel personalized medicine tool for assessing inherited colorectal cancer syndrome risk developed
December 11, 2018 - Study uncovers 11 new genes associated with epilepsy
December 11, 2018 - Filling research gaps could help develop more disability-inclusive workplaces
December 11, 2018 - Cartilage tissue engineering brings good news for patients with cartilage defects
December 11, 2018 - Novel 3D printing workflow helps predict leaky heart valves
December 11, 2018 - Imagination can help overcome fear and anxiety-related disorders, shows study
December 11, 2018 - Are caries linked to political regime?
December 11, 2018 - Leader in Diabetes Clinical Trials Wins Naomi Berrie Award
December 11, 2018 - Scientists discover cellular mechanism that triggers pneumonia in humans
December 11, 2018 - Increasing mental health problems related to drug use in over 55’s
December 11, 2018 - High-intensity interval exercise could help combat cognitive dysfunction in obese people
December 11, 2018 - Annual flu shot can save lives of heart failure patients
December 11, 2018 - Researchers compare health outcomes for VA and non-VA hospitals
December 11, 2018 - Recommendations Developed for Psoriatic Arthritis Treatment
December 11, 2018 - Genetic analysis links obesity with diabetes, coronary artery disease
December 11, 2018 - Study shows that having genetic information can affect how the body responds
December 11, 2018 - UNAIDS Report: 9 Million Are Likely HIV Positive And Don't Know It
December 11, 2018 - Lund University researchers succeed in obtaining dendritic cells by direct reprogramming
December 11, 2018 - Breast tumors recruit bone marrow cells to boost their growth, study reveals
December 11, 2018 - Updated breast cancer screening guideline highlights importance of shared decision-making
December 11, 2018 - EHR-related stress associated with physician burnout
December 11, 2018 - AHA: 12-Year-Old Heart Defect Survivor Inspires NFL Player’s Foundation
December 11, 2018 - Breast cancer patients who take heart drug with trastuzumab have less heart damage
December 11, 2018 - Providing aid to those humans – and animals – affected by the California fires
December 11, 2018 - Even without proof, CBD is finding a niche as a cure-all
December 11, 2018 - Drawing leads to better memory than writing
December 11, 2018 - Researchers report novel findings on plant hormone
December 10, 2018 - A Tale of Two Labels
December 10, 2018 - Triple combination cancer immunotherapy improves outcomes in preclinical melanoma model
December 10, 2018 - A 14-year-old explains what it’s like to get a new heart
December 10, 2018 - Team Players Honored with 2018 Baton Awards
December 10, 2018 - Global report highlights how the changing world is affecting children’s physical activity levels
December 10, 2018 - Genes play a role in physical activity and sleep
December 10, 2018 - DDT in Alaskan fish shown to increase risk of cancer
December 10, 2018 - Laws to curb use of cell phones have greatly reduced fatalities for motorcyclists
December 10, 2018 - Argenx Provides Detailed Data from Phase 2 Clinical Trial of Efgartigimod in Immune Thrombocytopenia and Phase 1/2 Clinical Trial of Cusatuzumab in Acute Myeloid Leukemia
December 10, 2018 - University of Maryland doctors treat first breast cancer patients with GammaPod radiotherapy
December 10, 2018 - The heartbeat seat: Demoing new well-being technologies in a car
December 10, 2018 - Leading Cancer Researcher to Direct Herbert Irving Comprehensive Cancer Center
December 10, 2018 - Researchers explore how glial cells develop in the brain from neural precursor cells
December 10, 2018 - Study compares pain-related diagnoses in First Nations and non-First Nations children, youth
December 10, 2018 - Experts address sleep disorders following traumatic brain injury
December 10, 2018 - Scientists find answers to how cancer spreads
December 10, 2018 - Study explores why older people read more slowly
December 10, 2018 - Smart life-collar could save lives of young children
December 10, 2018 - Asbestos found in most NHS hospitals finds BBC inquiry
December 10, 2018 - Researchers use new technique to probe hydrogen bonds
December 10, 2018 - Music improves social communication in autistic children
December 10, 2018 - Some Brain Tumors May Respond to Immunotherapy, New Study Suggests
December 10, 2018 - Banning junk food ads to combat childhood obesity
December 10, 2018 - Skin Autofluorescence Predicts T2DM, Heart Disease, Mortality
December 10, 2018 - Largest autism sequencing study to date yields 102 genes associated with ASD
December 10, 2018 - Statins associated with low risk of side effects
December 10, 2018 - Episodic memory tests help in predicting brain atrophy and Alzheimer’s disease
December 10, 2018 - Study explores how schools address adolescent self-harming practices
December 10, 2018 - Pregnancy in adolescence linked to increased risks of complications in young mothers
December 10, 2018 - Risk Analysis publishes special issue on communicating about Zika virus
December 10, 2018 - Botox May Help Prevent Post-Op A-Fib
December 10, 2018 - African-American mothers rate boys higher for ADHD
December 10, 2018 - Graphic warning labels cancel out cigarettes’ appeal to young people
December 10, 2018 - Australian researchers to study gas inhalational anaesthetic and likelihood of cancer return
December 10, 2018 - Individual neurons located within the brain have implications for psychiatric diseases
December 10, 2018 - Researchers improve bariatric surgery scoring system to extend prediction time for diabetic remission
December 10, 2018 - HPV type 16 or 18 associated with cervical cancer risk in young women
December 10, 2018 - Cervical cancer risk is higher in women with positive HPV, but no cellular abnormalities
December 10, 2018 - Combo therapy not needed if low RA disease activity achieved
December 10, 2018 - Novel therapeutic targets based on biology of aging show promise for Alzheimer’s disease
December 10, 2018 - UC San Diego professor receives NCI Outstanding Investigator Award for cancer research
December 10, 2018 - Study evaluates placental mesenchymal stem cell sheets for myocardial repair and regeneration
December 10, 2018 - Blueprint Medicines Announces Updated Results from Ongoing EXPLORER Clinical Trial of Avapritinib Demonstrating Broad Clinical Activity and Significant Symptom Reductions in Patients with Systemic Mastocytosis
December 10, 2018 - Study clarifies ApoE4’s role in dementia
December 10, 2018 - Eating disorders now a top priority with Australian Government
December 10, 2018 - Neuronal activity in the brain allows prediction of risky or safe decisions
December 10, 2018 - FDA Alerts Health Care Professionals and Patients Not to Use Drug Products Intended to be Sterile from Promise Pharmacy
December 10, 2018 - Improving dementia care and treatment saves thousands of pounds in care homes
December 10, 2018 - Heroin-assisted treatment can offer benefits, reduce harms
December 10, 2018 - People covered by Michigan’s expanded Medicaid program report improvements in health, finds study
Study reveals how dengue virus replicates without triggering the body’s defenses

Study reveals how dengue virus replicates without triggering the body’s defenses

image_pdfDownload PDFimage_print

A new study reveals how dengue virus manages to reproduce itself in an infected person without triggering the body’s normal defenses. Duke researchers report that dengue pulls off this hoax by co-opting a specialized structure within host cells for its own purposes, like a lazy roommate sneaking bits of his laundry into the communal wash.

Unlike other viruses that flagrantly disrupt the functions of the host in favor of their own needs, dengue appears to be more subtle. It slowly and surreptitiously takes over an accordion-shaped structure inside the cell called the endoplasmic reticulum, the production site for a small subset of host proteins, and steers clear of the larger fluid-filled space of the cell called the cytosol, where most cellular proteins are manufactured.

“It is a remarkably clever thing for a mere 10 kilobases of genetic information,” said Christopher V. Nicchitta, Ph.D., senior study author and professor of cell biology at Duke University School of Medicine. “The virus takes over the machinery and makes a ton of itself, but so slowly and inefficiently that it doesn’t set off any of the sensors the host cell uses to detect when something is awry.”

The study, which appeared January 10 in the Journal of Virology, could point to new strategies to thwart the mosquito-transmitted virus.

According to the World Health Organization, approximately half of the world’s population is at risk of dengue and each year, about 96 million people are sickened by it. No specific treatment for dengue fever currently exists. Decades of vaccine research have been met with disappointment, and recent reports indicate that a new vaccine for dengue could actually worsen the disease rather than prevent it.

“If you can’t make a vaccine, the approach you are left with involves understanding the precise molecular details of the life cycle of these viruses and how they are able to secure and manipulate the host machinery, so you can identify potential drug targets,” said Nicchitta. “It is a more difficult path, but we are beginning to map it out.”

Viruses like dengue are curious entities that exist in a realm between the living and the dead. Though they possess a few hallmarks of life — like proteins and genetic material (DNA or RNA) — they are missing a key one: the ability to reproduce. That’s where host cells come in. Shortly after a virus infects a living cell, it taps into the host’s replication machinery to make more copies of itself. In the case of dengue, one infected host cell can churn out as many as 10,000 viral offspring.

In this study, Nicchitta and his colleagues infected tissue culture cells with a common strain of dengue virus. They then sorted out the cell contents to focus on the two areas where proteins are typically synthesized, the endoplasmic reticulum and the neighboring cytosol. Using advanced molecular techniques, the researchers mapped out the location of the tiny factories known as ribosomes that produce proteins, as well as the RNA template that provides a blueprint for their production.

They found that all the action took place on the surface of the endoplasmic reticulum. The entire genome of the dengue virus is translated in one fell swoop, and then cut up into ten separate proteins. Adding such a complex product to the workload of the endoplasmic reticulum would typically set off its stress sensors. But the researchers discovered that the viral RNA template was translated into protein in such an inefficient, lackadaisical manner, that it didn’t trip those alarms.

“There are features of the RNA that makes it inefficiently translated, so it doesn’t turn on these stress pathways,” Nicchitta said. “Dengue keeps the host cells happy as long as it can. At some point it does gradually overburden the system and the cells will die, but by then the virus has already made tens of thousands of copies of itself.”

Nicchitta is currently trying to pinpoint which features of dengue — its sequence or structure, or both — underlie the slow and steady approach. It may sound counterintuitive, but he says that if the virus were translated more efficiently, it could no longer hide in plain sight. The host cell would notice, and the jig would be up.

Source:

https://today.duke.edu/2018/01/dengue-takes-low-and-slow-approach-replication

Tagged with:

About author

Related Articles