Breaking News
March 19, 2019 - Heart attack patients who are taken to heart care centres directly survive longer
March 19, 2019 - IVF babies have increased in birthweight over the past 25 years, study reveals
March 19, 2019 - Study highlights the need for psychiatric care to be integrated into cancer treatment
March 19, 2019 - Testosterone treatment lowers recurrence rates in low-risk prostate cancer patients
March 19, 2019 - Caterpillars could hold the secret to new treatment for Osteoarthritis
March 19, 2019 - Parkinson’s treatment delivers a power-up to brain cell ‘batteries’
March 19, 2019 - Stanford launches new Institute for Human-Centered Artificial Intelligence
March 19, 2019 - Wireless earphones may cause cancer
March 18, 2019 - ACC/AHA guideline for prevention of cardiovascular disease released
March 18, 2019 - UTA nursing professor receives $6.575 million to attack musculoskeletal diseases
March 18, 2019 - Gene medication shows promise to treat spinal cord injuries
March 18, 2019 - First Human Study of “Robotic” RaniPill™ Capsule to Replace Injections Announced by Rani Therapeutics
March 18, 2019 - Food Allergy Testing: MedlinePlus Lab Test Information
March 18, 2019 - Altered brain activity patterns of Parkinson’s captured in mice
March 18, 2019 - Apple Heart Study demonstrates ability of wearable technology to detect atrial fibrillation | News Center
March 18, 2019 - Cardiovascular benefits of diabetes drug extend across a wide spectrum of patients, shows study
March 18, 2019 - Novel cardiac pump shows superior outcomes in patients with advanced heart failure
March 18, 2019 - U.S. FDA Grants Priority Review for Fedratinib New Drug Application in Myelofibrosis
March 18, 2019 - Living like a caveman won’t make you thin—but it might make you healthy
March 18, 2019 - Modified immune cells issue alert when detecting cancer in mice | News Center
March 18, 2019 - Dementia caregivers design robots for alleviating stress and increasing joyful moments
March 18, 2019 - VR technology could help improve balance in humans
March 18, 2019 - Study demonstrates effective way to slow progression of cerebrovascular disease in older adults
March 18, 2019 - Premature babies also have protective anti-viral antibodies
March 18, 2019 - Painkillers taken by pregnant mothers unlikely to cause asthma in the child
March 18, 2019 - Fibromyalgia can be reliably detected in blood samples
March 18, 2019 - Marijuana use has dropped among most teens after legalization
March 18, 2019 - Legacy Pharmaceutical Packaging, LLC Issues Voluntary Nationwide Recall of Losartan Potassium Tablets, USP, 25mg, 50mg, And 100mg Due to The Detection of Trace Amounts Of N-Nitroso N-Methyl 4-Amino Butyric Acid (NMBA) Impurity Found in The Active Pharmaceutical Ingredient (API)
March 18, 2019 - Researchers identify early home and family factors that contribute to obesity
March 18, 2019 - Fate and festivity: Match Day 2019
March 18, 2019 - Study finds TAVR to be as good as open-heart surgery for patients at low surgical risk
March 18, 2019 - EU-funded project is developing new tools for diagnosing cancer
March 18, 2019 - Gluten, lactose, food dyes in pills could be causing side effects finds study
March 18, 2019 - Taking painkillers during pregnancy is not responsible for asthma risk in children, study shows
March 18, 2019 - Prediagnosis Psychiatric Care Linked to Worse Cancer Mortality
March 18, 2019 - Paris hospital halts stool study after donor deluge
March 18, 2019 - Partial oral antibiotic therapy shows efficacy and safety in patients with infectious endocarditis
March 18, 2019 - Olympus improves access to science education through BioBus collaboration
March 18, 2019 - Depression screening does not improve quality of life in heart attack patients
March 18, 2019 - Echocardiography may aid in patient selection for TMVR
March 18, 2019 - Are ‘Inactive’ Ingredients in Your Drugs Really So Harmless?
March 18, 2019 - Wearable technology can safely identify atrial fibrillation
March 18, 2019 - Scientists tackle rare retinal disease in unique research project
March 18, 2019 - Death By A Thousand Clicks
March 18, 2019 - Absorbable, antibiotic-eluting envelope can reduce rate of cardiac device infections
March 18, 2019 - Hormonal treatment associated with depression in men with prostate cancer
March 18, 2019 - Porvair Sciences launches reinforced 96-well deep round microplate
March 18, 2019 - Simplified catheter ablation could slash waiting lists for atrial fibrillation patients
March 18, 2019 - BFR therapy as part of rehabilitation following ACL surgery may slow bone loss
March 18, 2019 - A human model to test implants for cataract surgery
March 18, 2019 - New risk adjustment model could reduce financial penalty for safety net hospitals
March 18, 2019 - NHS cancer patients’ wait to start treatment worrying
March 18, 2019 - Inventiva Announces Results from Phase IIb Clinical Trial with Lanifibranor in Systemic Sclerosis
March 18, 2019 - Cologuard
March 18, 2019 - Researchers find evidence of prenatal environment tuning genomic imprinting
March 18, 2019 - Dolomite Bio launches novel Nadia product family for single-cell research
March 18, 2019 - Intellipharmaceutics Announces Resubmission of New Drug Application to the U.S. FDA for its Oxycodone ER
March 18, 2019 - Excessive gestational weight gain tied to maternal morbidity
March 18, 2019 - RCEM issues position statement on metrics to supplement four-hour standard target
March 17, 2019 - Noncontrast Brain MRI Effective for Monitoring Multiple Sclerosis
March 17, 2019 - Brain region plays key role in regulation of parenting behavior, study finds
March 17, 2019 - Natural speed limit on DNA replication sets pace for life’s first steps
March 17, 2019 - New research reveals overlooked impact of herbicide glyphosate on the environment
March 17, 2019 - Molecular patterns could help predict relapse risk in breast cancer patients
March 17, 2019 - Study confirms sensitivity of microbiological cultures for detecting cholera
March 17, 2019 - Scientists Spot Clues to Predicting Breast Cancer’s Return
March 17, 2019 - Scientists identify gene that keeps PTSD-like behavior at bay in female mice
March 17, 2019 - New method would allow doctors to detect earliest stages of cancers in the lymph nodes
March 17, 2019 - Cholesterol protein discovery raises hope for smarter drugs
March 17, 2019 - New insect medium delivers high viable cell density growth and protein yield
March 17, 2019 - Opioid crisis brings concerns about heart dangers
March 17, 2019 - Resistance Training May Prevent Type 2 Diabetes Progression
March 17, 2019 - Bioluminescence sensors make new approaches to drug discovery possible
March 17, 2019 - New FDA Rules Aim to Keep Kids From Flavored E-Cigarettes
March 17, 2019 - Vitamin B3 analogue boosts production of blood cells
March 17, 2019 - Government cuts to stop smoking services have detrimental impact on public health
March 17, 2019 - Common tool to assess potential adoptive parents lags behind societal changes
March 17, 2019 - Patients’ own cells could be the key to treating Crohn’s disease
March 17, 2019 - Diagnostic delays common in inflammatory bowel disease
March 17, 2019 - Study uncovers dramatic differences in the brains of Hispanics with dementia
Focus on resistance to HIV offers insight into how to fight the virus

Focus on resistance to HIV offers insight into how to fight the virus

image_pdfDownload PDFimage_print
HIV
Credit: CC0 Public Domain

Of the 40 million people around the world infected with HIV, less than one per cent have immune systems strong enough to suppress the virus for extended periods of time. These special immune systems are known as “elite controllers.” But how do they actually fight HIV? Canadian scientists think they’ve found an important clue.

Working in collaboration with a team from the Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), researchers at the Laboratory of Antiviral Immunity of Université du Québec à Trois-Rivières (UQTR) have found that genetic mutations affecting the capsid, the structure surrounding the HIV genome, make it possible for a protein called TRIM5α to trigger the immune system of elite controllers.

This discovery, recently published in PLOS Pathogens, sheds light on the role that TRIM5α plays in the human body. In elite controllers, the protein sets off a mechanism that protects against HIV-1, the type of HIV responsible for the global pandemic. “In most infected individuals, TRIM5α’s triggering ability is so weak that it has no effect on the virus, but in elite controllers, TRIM5α seems to play a role in naturally inhibiting HIV-1,” said lead author Natacha Mérindol, a postdoctoral researcher at the UQTR lab.

There is no vaccine or cure for HIV-1. That’s why it’s important to understand why the virus is naturally inhibited in elite controllers, said Mérindol, who works under the direction of UQTR medical biology professor Lionel Berthoux, head of the lab, and Dr.Cécile Tremblay, a professor at Université de Montréal’s Faculty of Medicine and a clinical researcher at CRCHUM.

Different from the vast majority

Elite controllers are HIV-infected people whose immune system performs better at fighting HIV-1 than in the vast majority of HIV patients. They are infected with the virus, but the infection is much weaker than usual. “They have very strong immune systems that can control the infection – it’s as if they were receiving treatment, even when they aren’t,” said Mérindol.

“Our HIV-positive patients played an essential role in making this research possible and we would like to thank them for their incredible generosity and availability,” said Tremblay, a microbiologist and infectious disease specialist at the CHUM. “It’s an important study that could advance research on HIV vaccines.”

“Thanks to the dedicated patients and researchers from different universities, we were able to learn more and advance the fight against HIV,” added Mohamed El-Far, a fellow researcher at CRCHUM.

Studies had previously suggested that TRIM5α helps protect against HIV-1, prompting the researchers to analyze the virus found in many elite-controller patients who are part of the Canadian Cohort of HIV+ Slow Progressors, a group administered by the Fonds de Recherche du Québec – Santé’s AIDS and Infectious Disease Network (FRQS-SIDA/MI). The researchers compared blood samples of patients from two cohorts (elite controllers and normal progressors) who weren’t undergoing retroviral treatment.

TRIM5α: under the microscope

“Our goal was to examine a specific part of the virus: the capsid – it’s the ‘virus coat,’ which determines sensitivity to TRIM5α,” explained Berthoux, who directed the study. The capsid’s role is to protect the virus’s ribonucleic acid (RNA), which holds its genetic information, but the body’s immune system attacks it through a variety of mechanisms.

Those attacks lead to mutations that help them escape some of the immune mechanisms involved. The research team observed that the capsid’s gene carries a high number of mutations, but that these mutations made HIV-1 sensitive to TRIM5α activity, leading the team to wonder about the effects of a TRIM5α attack on the capsid in elite controllers.

They found that, in these patients, the interaction between TRIM5α and the capsid triggers an antiviral state that reduces cellular sensitivity to HIV-1. The signal sent by TRIM5α is strong enough for the cell to become resistant in this subset of the patient population, whereas TRIM5α’s signal is not as effective in normal patients.

This mechanism could be used to develop immunity strategies that inhibit HIV-1. One possible therapeutic strategy would be to genetically modify TRIM5α to increase its triggering ability, which would ultimately protect people from HIV. Since TRIM5α’s activation capacity is too weak in normal patients, this would mean mutating TRIM5α to increase its capacity to target HIV-1, which would therefore reduce the capacity of HIV-1 to propagate in the patient.


Patients with rare natural ability to suppress HIV shed light on potential functional cure


More information:
Natacha Merindol et al. HIV-1 capsids from B27/B57+ elite controllers escape Mx2 but are targeted by TRIM5α, leading to the induction of an antiviral state, PLOS Pathogens (2018). DOI: 10.1371/journal.ppat.1007398


Provided by
University of Montreal

Citation:
Focus on resistance to HIV offers insight into how to fight the virus (2018, November 30)
retrieved 12 January 2019
from https://medicalxpress.com/news/2018-11-focus-resistance-hiv-insight-virus.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Tagged with:

About author

Related Articles