Breaking News
November 17, 2018 - New study finds less understanding and implementation of patient engagement
November 17, 2018 - New shoe insole technology could help diabetic ulcers heal better while walking
November 17, 2018 - New method to extend cell division and immortalization of avian-derived cells
November 17, 2018 - Australian Academy of Science urges parents to vaccinate children against meningococcal disease
November 17, 2018 - Hot water treatment may help improve inflammation and metabolism in sedentary people
November 17, 2018 - Researchers produce 3D chemical maps of small biological samples
November 17, 2018 - Must Blood Pressure Rise Wth Age? Remote Tribes Hold Clues
November 17, 2018 - Noonan Syndrome
November 17, 2018 - Interventions to delay and prevent type 2 diabetes are underused, researchers say
November 17, 2018 - Hackathon prize winner seeks to remotely monitor patient skin conditions
November 17, 2018 - Research team identifies Ashkenazi Jewish founder mutation for Leigh syndrome
November 17, 2018 - Gene editing could be used to halt kidney disease in patients with Joubert syndrome
November 17, 2018 - Study uncovers link between gut disruption and aging
November 17, 2018 - Teens more likely to pick up smoking after exposure from friends and family
November 17, 2018 - Nicoya designate the Institute for Stem Cell Biology and Regenerative Medicine as the OpenSPR Centre of Excellence
November 17, 2018 - new horizon in dental, oral and craniofacial research
November 17, 2018 - How does poor air quality affect your health?
November 17, 2018 - New device can regulate children’s blood glucose more like natural pancreas
November 17, 2018 - Game-Changers in Western Blotting and Protein Analysis
November 17, 2018 - FDA announces new actions to limit sale of e-cigarettes to youth
November 17, 2018 - Warmer winter temperatures related to higher crime rates
November 17, 2018 - MCO places increasing emphasis on helping people find and access healthy food
November 17, 2018 - Group of students aim to improve malaria diagnosis using old smartphones
November 17, 2018 - Transplantation of feces may protect preterm children from deadly bowel disease
November 17, 2018 - Researchers explore whether low-gluten diets can be recommended for people without allergies
November 17, 2018 - New and better marker for assessing patients after cardiac arrest
November 17, 2018 - For 7-year-old with failing bone marrow, a life-saving transplant | News Center
November 17, 2018 - New first-line treatment for peripheral T-cell lymphoma approved by FDA
November 17, 2018 - Artificial intelligence could be valuable tool to help young victims disclose traumatic testimony
November 17, 2018 - Breakthrough in the treatment of Restless Legs Syndrome
November 16, 2018 - FDA Approves Keytruda (pembrolizumab) for the Treatment of Patients with Hepatocellular Carcinoma (HCC) Who Have Been Previously Treated with Sorafenib
November 16, 2018 - Eagle Books | Native Diabetes Wellness Program
November 16, 2018 - Patients with common heart failure more likely to have lethal heart rhythms
November 16, 2018 - How AI could help veterinarians code their notes | News Center
November 16, 2018 - Bias-based bullying does more harm to students than generalized bullying
November 16, 2018 - Researchers find first direct evidence that cerebellum plays role in cognitive functions
November 16, 2018 - Non-coding genetic variant plays key role in endothelial function and disease incidence
November 16, 2018 - EMA recommends first all-oral treatment to tackle deadly sleeping sickness
November 16, 2018 - Drug used to treat dizziness may slow down growth of triple-negative breast cancer
November 16, 2018 - AHA: Icosapent Ethyl Cuts CV Risk From Elevated Triglycerides
November 16, 2018 - ‘Orphan’ RNAs make cancer deadlier, but potentially easier to diagnose
November 16, 2018 - Air Cube touches down at hospital | News Center
November 16, 2018 - CRISPR-based tool shown to enhance cell-based immunotherapy
November 16, 2018 - Mechanisms that govern HIV latency differ in the gut and blood, finds study
November 16, 2018 - Researchers unravel mystery of NPM1 protein in acute myeloid leukemia
November 16, 2018 - High school students less likely to select milk, fruit for lunch when fruit juice is available
November 16, 2018 - Football coaches with great emotional competence are more successful
November 16, 2018 - Researchers awarded $10 million grant to address root causes of asthma in Puerto Rico
November 16, 2018 - Health Tip: Manage Morning Sickness
November 16, 2018 - Long term exposure to road traffic noise linked with greater obesity risk
November 16, 2018 - Infant gut microbes altered by mother’s obesity may increase risk for future disease
November 16, 2018 - Immunotherapy combination and chemotherapy show encouraging results in Phase II acute myeloid leukemia study
November 16, 2018 - ACC Latin America Conference brings experts to discuss latest cardiovascular science
November 16, 2018 - Pooled analysis of Intersect ENT’s steroid releasing implants in patients after frontal sinus surgery to be published
November 16, 2018 - Expectations about pain intensity can become self-fulfilling prophecies
November 16, 2018 - NIH awards $3.4 million to UC researchers to study gastrointestinal lymphatic system
November 16, 2018 - Highlighting Advances in Bioengineering and Analytical Technologies with eBooks
November 16, 2018 - Scientist Dr David Taylor of MR Solutions is a finalist in the BMW i UK Tech Founder Awards
November 16, 2018 - Earlier treatment could help reverse autistic-like behavior in tuberous sclerosis
November 16, 2018 - Sucking your baby’s pacifier could improve their health
November 16, 2018 - Vegetables and salad may include bacteria that are resistant to antibiotics
November 16, 2018 - Autism linked to prolonged connection between brain regions
November 16, 2018 - Endocrine Society chooses four Diabetes Caucus leaders as winners of Diabetes Champion Award
November 16, 2018 - Brain and muscle cells found within kidney organoids
November 16, 2018 - Person’s sex hormones may play key role in trauma survival, finds study
November 16, 2018 - PTEN Genetic Test: MedlinePlus Lab Test Information
November 16, 2018 - Toxic metal pollution linked with development of autism spectrum disorder
November 16, 2018 - Calcified nodules in the retina increase risk for progression to late stages of AMD
November 16, 2018 - ZEISS teams up with arivis AG to offer complete 3D imaging solutions
November 16, 2018 - Georgia State professor receives $1.2 million grant to study how the brain controls eating behavior
November 16, 2018 - Specific bacterial toxins reduce number of cells suppressing immune response
November 16, 2018 - Review by ID physician improves outcomes for outpatient parenteral antimicrobial therapy
November 16, 2018 - Conditions that produce signs similar to arthritis
November 16, 2018 - New artificial intelligence-based method predicts treatment effectiveness
November 16, 2018 - AHA: Dapagliflozin Noninferior to Placebo for MACE in T2DM
November 16, 2018 - Surgery remains best treatment for appendicitis, Stanford study finds
November 16, 2018 - Non-surgical fistula creation system Ellipsys becomes key focus of attention at CiDA
November 16, 2018 - Researchers find no link between ‘allergy friendly’ dogs and lower risk of asthma
November 16, 2018 - Researchers elucidate new rules of connectivity of neurons in the neocortex
November 16, 2018 - Treating children with ‘bubble baby disease’
Discovery may help broaden the scope of defenses against HPV

Discovery may help broaden the scope of defenses against HPV

image_pdfDownload PDFimage_print

Yale Cancer Center (YCC) scientists have filled in a key gap in understanding the unusual route by which the Human papillomavirus (HPV) infects cells. Their findings, published online today in the journal Cell, may eventually help to broaden the scope of defenses against HPV and provide valuable clues for delivering drugs into cells.

HPV is a family of killers. Although there are effective vaccines against these viruses, they still cause about 5% of cancer deaths worldwide, including more than 250,000 women who die of cervical cancer each year.

“As viruses go, HPV is relatively simple,” said Daniel DiMaio, M.D., Ph.D., deputy director of YCC and professor of genetics, molecular biophysics and biochemistry, and therapeutic radiology at Yale School of Medicine. “HPV’s circular DNA is stored inside a protein capsule containing only two viral proteins. Most of this capsule is made up of a protein called L1, with smaller numbers of a protein called L2 largely buried in the L1 protein shell.”

This simple virus, however, follows a complicated path to get into a cell and then its nucleus.

In previous experiments, DiMaio and his colleagues showed that after HPV enters the cell in a membrane-bound sac called an endosome, the virus latches on to a cellular protein in the cytoplasm called retromer. The retromer protein carries the virus into a cellular transport mechanism known as the retrograde pathway, which then delivers the virus to the nucleus. The YCC team also found that retromer binds directly to the end of the HPV L2 protein.

But how does the L2 protein cross the endosome membrane into the cytoplasm in the first place, so that it can bind to the retromer?

In their latest study, the investigators discovered that a short segment of the L2 protein transfers the protein across the endosome membrane into the cytoplasm. The short segment turns out to be one of a group of peptides called cell-penetrating peptides (CPPs), named for their ability to carry cargoes into cells.

“CPPs were discovered 30 years ago, but we don’t have a clear idea what the vast majority of them do,” DiMaio said. “In our case, we’ve shown that this CPP carries a protein segment through an intracellular membrane and into the cytoplasm, where it can bind to another protein.”

“We are trying to exploit this new knowledge to develop novel ways to block HPV infection,” he said. As one important part of the work, his team developed an assay that can determine whether the L2 protein has crossed the endosome membrane. “You can imagine using the assay as a drug screen, to look for compounds that block that particular step of infection,” he noted

Many researchers have been intrigued by the possibility of using CPPs to deliver proteins and other molecules into cells as drugs. DiMaio pointed out that genomic sequencing of about 350 types of HPV has identified hundreds of variants of the L2 CPP, all evolved for their membrane-penetrating role over millions of years.

“With this study, we have uncovered an entirely new universe of CPPs,” he said. “Some of them may have very interesting and useful properties as drug delivery tools.”

Source:

https://www.yalecancercenter.org/

Tagged with:

About author

Related Articles