Breaking News
November 21, 2017 - Simple test could help predict best treatment for cystic fibrosis patients
November 21, 2017 - Diabetes patients’ immune system can regulate insulin production
November 21, 2017 - Simple mirror technique boosts the performance of diSPIM, study says
November 21, 2017 - FDA raids Florida stores that consumers use to buy drugs from Canada
November 21, 2017 - FDA Alert: Limbrel Capsules by Primus Pharmaceuticals: FDA Advisory
November 21, 2017 - Exploring the genetics of glaucoma and retinal development
November 21, 2017 - Study finds sensors to detect biomarkers
November 21, 2017 - Researchers develop simple test to predict T2D remission after bariatric surgery
November 21, 2017 - Penn researchers find evidence of new malaria species in wild bonobos
November 21, 2017 - Review examines effectiveness of lipid-based products to treat dry eye disease
November 21, 2017 - Pioneering research project aims to develop better diagnostic tests for NAFLD
November 21, 2017 - The Best and Worst Ways to Say ‘I Love You’
November 21, 2017 - Even Partial Breast-Feeding for First Few Months Lowers SIDS Risk: MedlinePlus Health News
November 21, 2017 - Researchers identify protein that plays key role in diabetic blindness
November 21, 2017 - Sensors for identifying biomarkers could help detect myriad of diseases at early stages
November 21, 2017 - Scientists develop new method to study Creutzfeldt-Jakob disease in the lab
November 21, 2017 - Researchers identify previously unknown breast cell types
November 21, 2017 - Probing living cells with AFM
November 21, 2017 - Streamlined method for using CGM helps patients with diabetes maintain safe, stable glucose levels
November 21, 2017 - Even Advanced Breast Cancer Patients Gain From Exercise: MedlinePlus Health News
November 21, 2017 - Study in mice finds dietary levels of genistein may adversely affect female fertility
November 21, 2017 - Disordered eating has detrimental effects to long-term health of young adults, study finds
November 21, 2017 - Babies know more than we think they do find researchers
November 21, 2017 - New technique may reveal clues about role of centromeres in Down syndrome, other birth defects
November 21, 2017 - IUD May Lower Cervical Cancer Risk: MedlinePlus Health News
November 21, 2017 - U.S. preemie birth rates rise two years in a row
November 21, 2017 - Heart rate variability measured by electrocardiogram can help differentiate bipolar from major depression
November 21, 2017 - $10 million gift creates new center at Northwestern University to study effects of environment on genes
November 21, 2017 - Uncontrolled lung diseases could lead to costly A&E visits and hospital stays
November 21, 2017 - New study explores patients’ and family members’ views on overlapping surgeries
November 21, 2017 - KNAUER celebrates 55th anniversary and awards science prize
November 21, 2017 - Researchers find new way to boost cancer-destroying ability of T-cells
November 21, 2017 - Maintaining adequate vitamin D may help prevent onset of inflammatory diseases
November 21, 2017 - What NPs Can Do in the Opioid Crisis
November 21, 2017 - Gun Injuries Getting More Severe, Experts Say: MedlinePlus Health News
November 21, 2017 - That music playing in your head is a real conundrum for scientists
November 21, 2017 - Researcher awarded $1.5 million to study role of tumor necrosis factor in IBD
November 21, 2017 - Digital pills can help track opioid use patterns
November 21, 2017 - UZH leads Europe’s largest research on aging
November 21, 2017 - Experts endorse recommendations for restrictive blood transfusions
November 21, 2017 - New Hemophilia A Treatment, Hemlibra (Emicizumab-kxwh), Stems Bleeding Episodes
November 21, 2017 - Shining a light on the nervous system to thwart disease
November 21, 2017 - Use of Prostate Health Index cuts down need for uncomfortable biopsies
November 21, 2017 - Drugstore pain pills as effective as opioids in ER patients
November 21, 2017 - Experts explain why lead found in fidget spinners is no idle threat
November 21, 2017 - Over-the-counter decongestant found to be effective inhibitor of tumor stroma
November 21, 2017 - Anticholinergic Cognitive Burden Scale shows dose-response relationship with adverse outcomes
November 21, 2017 - Non-vitamin K antagonist oral anticoagulants linked to reduced kidney risks
November 21, 2017 - New technique holds promise to screen cancer cells for drug susceptibility
November 21, 2017 - AstraZeneca wins US approval for lymphoma drug
November 21, 2017 - Mother’s diet can protect nursing newborns against food allergies, research shows
November 21, 2017 - Cystic fibrosis patients have more good and bad bacteria in their lungs, study finds
November 21, 2017 - Patient-centered medical home model effective at improving chronic disease outcomes
November 21, 2017 - Enterovirus vaccine protects against virus-induced diabetes in mouse model
November 20, 2017 - First-of-its-kind study combines smoking cessation with personalized medicine
November 20, 2017 - FDA Approves Sutent (sunitinib malate) for Adjuvant Treatment of Adult Patients at High Risk of Recurrent Renal Cell Carcinoma
November 20, 2017 - Researchers produce the first draft cell atlas of the small intestine
November 20, 2017 - Study explores feasibility of mainstreaming genetic counseling for ovarian cancer
November 20, 2017 - AAP and The Obesity Society jointly address weight stigma in childhood obesity
November 20, 2017 - Researchers identify three specific molecules that accurately indicate pre-diabetes
November 20, 2017 - Study estimates health care costs, injuries, and deaths due to motorcycle accidents
November 20, 2017 - Face It: Drinking, Smoking Takes Toll on Looks
November 20, 2017 - Women have lower tolerance to alcohol following gastric sleeve surgery, study finds
November 20, 2017 - Salt, inflammation and hypertension
November 20, 2017 - Electrochemistry method provides easy access to important classes of compounds
November 20, 2017 - Cancer drugs may offer new way to control high blood pressure
November 20, 2017 - Small molecules in saliva may offer clues to diagnose and predict duration of concussions
November 20, 2017 - New poll demonstrates challenge of finding childcare options that meet parent’s safety criteria
November 20, 2017 - Canadians root for an underdog U.S. health policy idea
November 20, 2017 - KAIST researchers identify principles of gene network for colon tumorigenesis
November 20, 2017 - Pregnant mother in a coma wakes three months after delivery
November 20, 2017 - VTT researcher develops disposable optical test substrate for microbial detection
November 20, 2017 - Benzodiazepines linked to increased risk of death among Alzheimer’s disease patients
November 20, 2017 - Women are advised that sleeping on their side could reduce stillbirth risk
November 20, 2017 - The skinny on lipid immunology
November 20, 2017 - Study sheds light on changes in young people’s sexual practices
November 20, 2017 - Study highlights need for early identification, treatment of PTSD in cancer survivors
November 20, 2017 - FDA approves remote programming feature for Nucleus Cochlear Implant System via telemedicine
November 20, 2017 - The One Patient That We Neglect Too Often
November 20, 2017 - The battle between cancer and the immune system—who switches the off signals off?
Specific way of spelling out genetic code likely allows viruses to evade our cellular defenses

Specific way of spelling out genetic code likely allows viruses to evade our cellular defenses

image_pdfDownload PDFimage_print

For millions of years, humans and viruses have engaged in a constant tug of war: as our cells evolve new ways to defend us from our viral enemies, these pathogens in turn acquire new traits to sidestep those defenses.

Now, scientists have found that a key similarity between our genes and those of many viruses–a way of spelling out the genetic code – has likely allowed viruses to evade our cellular defenses. Paul Bieniasz, a Rockefeller professor and Howard Hughes Medical Institute Investigator who led the work, says it began as an effort to understand how the viral genome affects the infectious potency of HIV, the virus that causes AIDS.

Reported in Nature, his lab’s recent findings offer insight into our cellular defense mechanisms, and suggest novel avenues for vaccine development.

Surprisingly enough, it all comes down to a matter of spelling.

There are a handful of words in the English language whose spellings can vary without changing their meaning: colour and color, for example, or traveler and traveller. Our genome is no different: there are many different ways of spelling the molecular code that makes up our genes without changing the proteins those genes produce. But Bieniasz and his colleagues found that for HIV and other viruses, certain spellings, or specific variants in the genetic code, are critical for viral replication and infection.

Two adjacent letters, lost in evolution

All genomes are strings of small molecules, known as bases, that are represented by letters such as C, G, and A. String those letters out in a particular order, and they spell a word, or gene, that produces a particular protein. In seeking to identify parts of the HIV genome that enable infection, the researchers generated mutant versions of the virus. But rather than changing the proteins spelled out through its genetic letters, they introduced alternate spellings for the genes, keeping the proteins unchanged.

The research team found that some of these viral mutants were unable to grow and replicate. “Intuitively, this is unexpected, because all of the proteins–the workhorses of the virus–are exactly the same,” Bieniasz explains.

The defective mutant viruses had one thing in common, however: they all contained multiple instances of a particular two-letter sequence: CG.

That two-letter sequence doesn’t seem like a terribly unlikely occurrence. There are just four letters in the genetic code, so the probability of finding any two letters together is high–1 in 16, to be exact. And yet, by an odd coincidence of evolution, the CG sequence is rare in human DNA. When placed side by side, the letter C can be modified in a chemical reaction that ultimately leads to its replacement by a different letter.

“Because of this evolutionary loss, the human genome now has about 80 percent fewer CG sequences than we would expect by chance,” explained graduate student Matthew A. Takata, lead author of the new paper.

A bull’s eye for the immune system

We humans are not alone in lacking CG sequences: normal HIV and many other viruses lack them too, but for different reasons. “Many viral genomes cannot go through the same chemical modification process that vertebrate genomes like our own have experienced,” Bieniasz said. “This led us to ask: How and why did HIV and other viruses lose their CG sequences?”

The researchers hypothesized that a cellular surveillance system might exist to identify and destroy CG sequences, thereby preventing viral infection. Bieniasz, Takata, and the research team exploited novel gene editing technology to search for proteins that might serve as such a defense mechanism. They found that in human cells, an antiviral protein called “ZAP” (Zinc-finger Antiviral Protein) can recognize molecules that have many CG sequences. ZAP binds to the sequences, identifying them as the mark of a foreign invader. These viral genomes are then destroyed.

The results offer insight into what caused HIV and other viruses to lose their CG sequences over time. These viruses have likely adapted to mammalian defense mechanisms, evolving to remove CG sequences and avoid surveillance by ZAP.

Although many animal viruses like HIV contain few CG sequences, and hence don’t get destroyed by ZAP, the researchers speculate that the protein still serves to protect us against other pathogens. “Its activity enables cells to recognize foreign invaders as ‘non-self,'” Bieniasz says, ” and may provide defense against viruses from other species, such as biting insects, whose genomes still have high numbers of CG sequences.”

Practically, the discovery may be useful in developing the weakened, or attenuated, viruses that are often used to make vaccines. By genetically engineering a virus to contain an increased number of CG sequences, researchers could potentially come up with a version that would prompt people’s immune systems to produce immunity against the pathogen without actually making them sick.

“Recoding a virus with many additional CG sequences,” says Takata, “is likely to be an effective, adjustable and largely irreversible way of attenuating it, making vaccine development faster and safer.”

Source:

https://www.rockefeller.edu/news/20795-in-the-fight-against-viral-infection-spelling-counts/

Tagged with:

About author

Related Articles