Breaking News
March 23, 2019 - Lung cancer survivor recounts her lifetime struggles
March 23, 2019 - Radial and femoral approach for PCI achieve similar results in terms of survival
March 23, 2019 - Study sheds light on the optimal timing of coronary angiography in NSTEMI patients
March 23, 2019 - Excess hormones could cause a condition that can lead to blindness in women, study finds
March 23, 2019 - Dramatic shifts in first-time opioid prescriptions bring hope, concern
March 23, 2019 - Antidepressant drugs may not work when neurons are out of shape
March 23, 2019 - TTUHSC El Paso to establish endowed chair in neurology through a major grant
March 23, 2019 - New device approved by FDA for treating patients with moderate-to-severe heart failure
March 23, 2019 - People with peripheral artery disease have lower Omega-3 Index, shows research
March 23, 2019 - Trigger warnings have minimal impact on how people respond to content, shows research
March 23, 2019 - Gilead Announces Data From Two Studies Supporting Further Development of GS-6207, a Novel, Investigational HIV-1 Capsid Inhibitor as a Component of Future Long-Acting HIV Therapies
March 23, 2019 - Selfish genetic elements amplify inflammation and age-related diseases
March 23, 2019 - Study provides new understanding of how the brain recovers from damage caused by stroke
March 23, 2019 - CRISPR/Cas libraries could revolutionize drug discovery
March 23, 2019 - Allergic reaction during pregnancy may alter sexual-development in offspring’s brain
March 23, 2019 - Seeing through a robot’s eyes helps those with profound motor impairments
March 23, 2019 - Recent research shows that ease of breastfeeding after C-section differs culturally
March 23, 2019 - Newly discovered parameters offer more control over efficient release of drugs
March 23, 2019 - ‘De-tabooing’ of abortion- Women would like more support from health care community
March 23, 2019 - Anti-TB drugs can increase susceptibility to Mtb reinfection
March 23, 2019 - New survey indicates need of attention to neglected tropical diseases
March 23, 2019 - Innovative in vitro method to develop easy-to-swallow medicine for children and older people
March 23, 2019 - Sugary drinks could raise risk of early deaths finds study
March 23, 2019 - Lian wins ENGINE grant for stem-cell-based therapy to treat Type 1 diabetes
March 23, 2019 - Overall, Physicians Are Happy and Enjoy Their Lives
March 23, 2019 - Researchers discover how blood vessels protect the brain during inflammation
March 23, 2019 - CDC study shows modest improvement in optimal hospital breastfeeding policy
March 23, 2019 - Family-based prevention program to reduce alcohol use among older teens
March 23, 2019 - Remote monitoring of implanted defibrillators in heart failure patients prevents hospitalizations
March 23, 2019 - Appropriate doffing of personal protective equipment may reduce healthcare worker contamination
March 23, 2019 - Window screens can suppress mosquito populations, reduce malaria in Tanzania
March 23, 2019 - Researchers discover new biomarker for postoperative liver dysfunction
March 23, 2019 - Pregnancy history may be linked to cognitive function in older women, finds study
March 23, 2019 - Study shows ticagrelor is equally safe and effective as clopidogrel after heart attack
March 23, 2019 - FDA Approves First Drug for Postpartum Depression, Zulresso (brexanolone)
March 23, 2019 - New guidelines outline new treatment management for psoriasis
March 23, 2019 - Thermally abused cooking oil may promote progression of breast cancer
March 23, 2019 - High-fructose corn syrup fuels growth of colon tumors in mice
March 23, 2019 - Partnership aims at establishing best practices to promote diversity in clinical trials
March 23, 2019 - New study examines presence of microbes in tap water from residences, office buildings
March 23, 2019 - Early life trauma may affect brain structure, contribute to major depressive disorder
March 23, 2019 - NIH starts clinical trial of drug to treat cravings associated with opioid use disorder
March 23, 2019 - Cervix bacteria, immune factors could be a warning signal of premature birth, reports new research
March 23, 2019 - Worst-ever emergency care performance figures underscore the need to focus on staffing
March 23, 2019 - The Current issue of “The view from here” is concerned with Cancer
March 23, 2019 - Mouse model validates how ‘good’ and ‘bad’ bacteria affect acne
March 23, 2019 - Individual amygdala neurons respond to touch, imagery and sounds
March 23, 2019 - Combination of two topical creams can prevent cancer
March 23, 2019 - Study suggests depression screening when assessing African-Americans for schizophrenia
March 23, 2019 - New electronic support system for choosing drug treatment based on patient’s genotype
March 23, 2019 - First-of-its-kind study provides pregnancy statistics of imprisoned U.S. women
March 23, 2019 - Marinus Pharmaceuticals Initiates Phase 3 Study in Children with PCDH19-Related Epilepsy
March 23, 2019 - Laparoscopy: MedlinePlus Lab Test Information
March 23, 2019 - Shellfish allergies: can they be treated?
March 23, 2019 - Toilet seat heart monitoring system
March 23, 2019 - Researchers identify way to improve common treatment for PTSD
March 23, 2019 - High potency cannabis use linked to psychosis finds study
March 23, 2019 - Evoke Pharma Submits Response to FDA Review Letter for Gimoti NDA
March 23, 2019 - Tracking HIV’s ever-evolving genome in effort to prioritize public health resources
March 23, 2019 - Scientists grow most sophisticated brain organoid to date
March 23, 2019 - ADHD drug raising risk of psychosis
March 22, 2019 - FDA approves brexanolone, first drug developed to treat postpartum depression
March 22, 2019 - Gruesome cat and dog experiments by the USDA exposed
March 22, 2019 - Ball pits used in children’s physical therapy may contribute to germ transmission
March 22, 2019 - Long-term use of inexpensive weight-loss drug may be safe and effective
March 22, 2019 - FDA Approves Sunosi (solriamfetol) for Excessive Daytime Sleepiness Associated with Narcolepsy or Obstructive Sleep Apnea
March 22, 2019 - Anti-Müllerian Hormone Test: MedlinePlus Lab Test Information
March 22, 2019 - Finding the right exercise, diet aids for HIV patients
March 22, 2019 - Health Plans For State Employees Use Medicare’s Hammer On Hospital Bills
March 22, 2019 - Researchers develop new tool for imaging large groups of neurons in living animals
March 22, 2019 - Certain bacteria and immune factors in vagina may cause or protect against preterm birth
March 22, 2019 - Research identifies guidelines for prioritizing hepatitis C treatment in U.S. prisons
March 22, 2019 - Novel breath test could pave new way to non-invasively measure gut health
March 22, 2019 - Pharmaceutical and personal care products may result in new contaminants in waterways
March 22, 2019 - New model could revolutionize the way researchers investigate spread of pathogens
March 22, 2019 - MSU professor receives NSF CAREER grant for biosensor diagnostics
March 22, 2019 - High-fat, high-sugar diet in mouse mothers causes problems in the hearts of offspring
March 22, 2019 - ACC: Catheter Ablation Does Not Cut Mortality, Stroke in A-Fib
March 22, 2019 - Wiedemann-Rautenstrauch syndrome – Genetics Home Reference
March 22, 2019 - Health insurance is not assurance of healthcare
Researchers find new way to defeat HIV latency

Researchers find new way to defeat HIV latency

image_pdfDownload PDFimage_print
HIV infecting a human cell. Credit: NIH

HIV, the virus that causes AIDS, has a secret life. Though anti-retroviral therapy can reduce its numbers, the virus can hide and avoid both treatments and the body’s immune response.

Researchers at UC Davis Health, together with colleagues at UC San Francisco and the University of North Carolina at Chapel Hill, have found that increased crotonylation, an epigenetic mechanism that governs gene expression, might be the key to making HIV come out of hiding and become susceptible to anti-HIV drugs. Their study is published in The Journal of Clinical Investigation.

“We have been working on mechanisms that could be used to disrupt HIV latency,” said Satya Dandekar, chair of the UC Davis Department of Medical Microbiology and Immunology and senior author on the paper. “The goal is to force the virus to be expressed so it is visible to the immune system and can be targeted through immuno-therapeutics. This is the first study to identify histone crotonylation as a driver for HIV transcription and de-crotonylation of histone as an epigenetic marker for HIV silencing.”

While medical science has transformed HIV/AIDS from a deadly disease to a chronic one, there are still millions of people living with the virus. HIV’s ability to become dormant makes it invisible to both the immune system and treatments. Researchers have dedicated years to deciphering the mechanisms that help HIV hide and finding ways to reverse that process.

In this study, the researchers focused on histone crotonylation, an epigenetic mechanism that modifies the proteins that package DNA, affecting gene expression.

“Histone crotonylation regulates HIV latency,” said UC Davis associate project scientist Guochun Jiang, first author on the paper. “If we can modulate that, the virus can be more efficiently flushed out.”

To better understand this mechanism, the team focused on an enzyme called ACSS2, which plays an important role in fatty acid metabolism in the gut. HIV has often been linked to impairment of lipid metabolism, making ACSS2 a promising potential target for an HIV cure.

To test it out, the researchers studied peripheral blood samples from HIV-infected patients and several HIV latency cell models. Activating the ACSS2 enzyme increased viral transcription manifold. The results from patient samples were particularly encouraging.

“We examined well-characterized cell models of HIV latency and immune cells from HIV patients who had been undergoing antiretroviral therapy and had undetectable viral loads,” Dandekar said. “In those samples, we were able to disrupt the HIV silencing by inducing histone crotonylation.”

To further validate the results, the researchers treated samples with an ACSS2 inhibitor, which reduced detectable virus levels, highlighting the important role of decrotonylation in establishing HIV latency.

One of the more intriguing findings in the study was that increasing histone crotonylation works synergistically with other known anti-HIV latency molecules, such as the protein kinase C agonist PEP005 and the HDAC inhibitor vorinostat. Dandekar and her colleagues are now searching for more molecules that attack viral latency to develop an overall strategy of combining therapeutic agents to compel HIV expression.

“We are looking for synergistic disruption, by combining histone crotonylation with other mechanisms to reactivate HIV,” Dandekar said. “This research positions us to screen and identify small molecules, which can be optimized to carry out HIV modification.”


Explore further:
Waking up HIV: Two compounds show great potential to rouse latent virus

More information:
Guochun Jiang et al, HIV latency is reversed by ACSS2-driven histone crotonylation, Journal of Clinical Investigation (2018). DOI: 10.1172/JCI98071

Journal reference:
Journal of Clinical Investigation

Provided by:
UC Davis

Tagged with:

About author

Related Articles