HIV is a chronic viral infection that attacks the immune system, eventually incapacitating its ability to fight infection leaving the person vulnerable to the development of AIDS, which often leads to death. Anti-retroviral therapies can help to control the virus, but complete eradication of the virus has been tricky to achieve due its stealthy ability to hide from the immune system.
HIV is unable to reproduce itself, so it relies on hijacking cellular machinery in order to ensure its survival. Medical advancements have allowed HIV/AIDS to become less deadly, but the virus has not yet been completely eradicated, and millions of people all over the world still suffer.
Scientists from UC Davis, UC San Francisco, and UNC at Chapel Hill have collaborated on a study to uncover the secrets of HIV latency and how to bring the sneaky virus out of hiding to enable successful treatments. Epigenetics has been at the forefront of the combat against HIV, and in this study published in the Journal of Clinical Investigation, the research team discovered that an epigenetic mechanism called crotonylation may hold the key to accomplishing this feat.
Crotonylation is a recently discovered post translational histone modification to lysine, and is a main factor in the control of gene expression, much like its cousin acetylation. Discovered by Dr. Yingming Zhao in 2011, crotonylation is the process of increasing the concentration of enzyme crotonyl-CoA at the lysine in order to increase transcriptional activity, ultimately enhancing gene expression.
This is done through crotonyltransferase p300, which is also a catalyst in histone lysine . Crotonylation has been shown to increase transcriptional activity more potently than acetylation, making it a promising research subject, especially in the future of HIV latency research.
The team led by Satya Dandekar, chair of the UC Davis Medical Microbiology and Immunology Department, examined blood samples from HIV positive patients and HIV latency cell models that were undergoing anti-retroviral therapies.
Satya Dandekar, chair of the UC Davis Department of Medical Microbiology and Immunology and senior author on the paper. Image Credit: UC Davis Health
They aimed their focus at a gut enzyme called ACSS2, which is one of the enzymes responsible for fatty acid metabolism in the digestive tract. HIV has often been associated with difficulties in metabolizing lipids, making this enzyme the perfect target for developing a potential cure.
They found that the induction of ACSS2 has a direct impact on stimulating histone crotonylation, which reinstated viral transcription, ultimately exposing the virus from hiding. The researchers then treated the blood samples with an ACSS2 inhibitor to limit the activity of the enzyme, which decreased the amount of histone crotonylation. In this environment, transcription of the virus could not be reactivated and remained dormant, further confirming the importance that crotonylation has in defeating HIV latency.
The researchers also learned that histone crotonylation can work in harmony alongside the HDACinhibitor vorinostat, and the protein kinase C agonist PEP005, both of which have had success in anti-HIV latency. Dandekar hopes to utilize this information to help create a super-immunotherapy that will prevent HIV latency.
“We are looking for synergistic disruption, by combining histone crotonylation with other mechanisms to reactivate HIV,” she said.
The data uncovered in this study provide valuable insights on future treatments for HIV. The elusiveness of the virus has previously hindered the success of various treatments. Hopefully, future studies can highlight the importance of histone crotonylation in rejuvenating the virus to present itself to the immune system in the effort to achieve complete HIV eradication.
Source: Satya Dandekar et al. (2018) HIV latency is reversed by ACSS2-driven histone crotonylation. Journal of Clinical Investigation, 128 (3): 1190.
Reference: UC Davis Health. “UC Davis researchers find new way to defeat HIV latency” UC Davis. 7 March 2018. Web.
- What is Epigenetics?
- Viruses Could Epigenetically Modify a Person’s DNA
- Harnessing Epigenetics to Prevent the Immune System from Attacking Itself
- Epigenetics, Nutrition, and Our Health: How What We Eat Could Affect Tags on Our DNA
- Click to share on Tumblr (Opens in new window)
- Click to share on Pocket (Opens in new window)
- Click to print (Opens in new window)
- Click to email this to a friend (Opens in new window)
- Click to share on StumbleUpon (Opens in new window)
- Click to share on Reddit (Opens in new window)
- Click to share on WhatsApp (Opens in new window)
- Click to share on Telegram (Opens in new window)
- Click to share on Facebook (Opens in new window)
- Click to share on Twitter (Opens in new window)
- Click to share on Pinterest (Opens in new window)
- Click to share on Skype (Opens in new window)
Published by dreddymd
Dr Eddy Bettermann MD focus on Biological Medicine (Biologische Medizin), Darkfield Microscopy (Dunkelfeld Mikroskopie), Orthomolecular Medicine (Orthomolekulare Medizin), Ayurvedic Medicine (Ayurveda), Psychosomatic Medicine (Psychosomatische Medizin), raw food (Rohkost), fasting (Fasten): Our primary integrative medicine goal is the maintenance of your health and wellness, and we are committed to safe and effective healthcare. Our specialties include online integrative medicine education by alternative doctor: food and allergy management through the use of Integrative medical therapy, Environmental Medicine, General Family Medicine, Ayurveda, Panchakarma, Chronic Fatigue, ADHD, autism, Fibromyalgia, Yeast/Fungus related diseases – Candidacies, mercury dental replacement and detoxification, Natural Thyroid Replacement, Weight loss, Lyme Disease, Irritable Bowel Disease, Attention Deficit Disorder, Pervasive Developmental Disorders, Multiple Chemical Sensitivities, Addiction related programs, Intestinal Dysbiosis, as well as trigger point therapy using Neural Therapy. Dr. Eddy Bettermann MD, physician from Germany, consultant and teacher in biological medicine, especially dark field microscopy known as Live Blood Analysis in Thailand, Malaysia, Hon Kong, Singapore and the Philippines. But he lecture also in the USA, Canada and the U.A.E. He speaks english and german. https://dreddymd.com/2017/01/17/the-interactive-live-blood-cd-and-the-certified-training-live-blood-analysis-online-course/ https://dreddymd.com/courses/ https://dreddymd.com/2017/01/17/live-blood-microscopy-analysis-darkfield-course/ “Let thy Food be thy Medicine and thy Medicine be thy Food.” — Hippocrates Physician Member of the Medical Board at AOX Singapore, Medical Doctor at Nurse Mobile Clinic and Physician at DrEddy Clinic Our Mission: The mission of the Integrative Medicine is to search for the most effective treatments for patients by combining both conventional and alternative approaches that address all aspects of health and wellness – biological, psychological, social and spiritual. Biological Medicine is a big part of my work and so is Dark field Microscopy, what I use in my daily practice and what I teach more then 15 years in Asia and around the world: Live Blood Analysis in dark field based on Haematology. We utilize Live blood analysis since 2004, conventional as well as specialty laboratories for a thorough diagnostic work up of the disease in question. Our integrative medicine treatment regimens are especially unique and are tailored specifically to the individual needs of each patient. Our Mission: don’t harm, prevent, use food as medicine We are a reliable partner for integrative medicine in Medical Spa & Clinic Development and integrative medicine Education Training for alternative doctors – we bring different holistic approaches, like Integrative Medicine, Traditional Chinese Medicine and Ayurveda Medicine together. On your request we offer our service in your place as well. Heavy metal poisoning Heavy metal poisoning is much more common than most people realize, and if you’re thinking that it doesn’t apply to you because you haven’t been exposed to any, think again. If you’ve eaten fish regularly, had amalgam fillings, received vaccinations, drank contaminated water, or done industrial or agricultural work or pharmaceutical manufacturing, there’s a good chance that you have a fair amount of toxic metals in your system.. We are here to help and to educate! Wishing your health and happiness Dr Eddy Bettermann MD Protect you and your family from harmful radiation https://bit.ly/synergyscience-dreddymd More information about 5G and EMF: https://dreddymd.com/?s=5G+and+EMF View all posts by dreddymd