Breaking News
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Catalyst Biosciences Presents Updated Data from Its Phase 2/3 Trial of Subcutaneous Marzeptacog Alfa (Activated) in Individuals with Hemophilia A or B with Inhibitors at the 12th Annual EAHAD Congress
February 16, 2019 - Rerouting nerves during amputation reduces phantom limb pain before it starts
February 16, 2019 - A Hormone Produced When We Exercise Might Help Fight Alzheimer’s
February 16, 2019 - Millions of British people breathe toxic air travelling to GPs
February 16, 2019 - Conformance of genetic characteristics found to be crucial for longer preservation of kidney graft
February 16, 2019 - Researchers use optogenetic tool to control, visualize receptor signals in neural cells
February 16, 2019 - New reversible antiplatelet therapy could reduce risk of blood clots, prevent cancer metastasis
February 16, 2019 - Testosterone is not the only hormone needed for penis development
February 16, 2019 - FDA Advisory Committee Recommends Approval of Spravato (esketamine) Nasal Spray for Adults with Treatment-Resistant Depression
February 15, 2019 - Heart surgery technology developed at Baptist Health debuts after years of secrecy
February 15, 2019 - Prescription Opioids Double Risk of Triggering Fatal Car Crash
February 15, 2019 - New study helps doctors better understand high blood pressure in pregnant women
February 15, 2019 - Beta wave control in Parkinson’s diseased brain could be a potential therapy
February 15, 2019 - Media representations of love may justify gender-based violence in young people
February 15, 2019 - Yoga May Help With Rheumatoid Arthritis Symptoms, Severity
February 15, 2019 - Obstructive sleep apnea linked to inflammation, organ dysfunction
February 15, 2019 - Master your mind: A challenge from WELL for Life
February 15, 2019 - Why Some Brain Tumors Respond to Immunotherapy
February 15, 2019 - Must-Reads Of The Week From Brianna Labuskes
February 15, 2019 - Researchers uncover novel mechanism and potential new therapeutic target for Alzheimer’s
February 15, 2019 - Genetic variations in a fourth gene associated with higher ALL risk in Hispanic children
February 15, 2019 - Disruptive behavioral problems in kindergarten linked with lower employment earnings in adulthood
February 15, 2019 - New bioengineered device enhances the production of T-cells
February 15, 2019 - HDL proteome behaves like a tiny Velcro ball that is rolling on surfaces
February 15, 2019 - Puerto Rican children more likely to have poor or decreasing use of asthma inhalers
February 15, 2019 - Quality of patient care does not improve after physician-hospital integration
February 15, 2019 - Synopsys release new software for implant design and patient-specific planning
February 15, 2019 - 6 out of 10 hip replacements last 25 years or longer
February 15, 2019 - Health Tip: What You Should Know About Antibiotics
February 15, 2019 - New research challenges medical consensus that adenoids and tonsils significantly shrink during teenage years
February 15, 2019 - Discovery of weakness in a rare cancer could be exploited with drugs
February 15, 2019 - UVA scientists find potential explanation for mysterious cell death in Alzheimer’s, Parkinson’s
February 15, 2019 - New rules requiring female athletes to lower testosterone levels are based on flawed data
February 15, 2019 - Researchers comprehensively sequence the human immune system
February 15, 2019 - Researchers study animal venoms to identify new medicines for treating diseases
February 15, 2019 - Movement of wrist bones revealed by MRI and computer modeling
February 15, 2019 - Philips introduces new premium digital X-ray room to help shorten patient wait times
February 15, 2019 - Women fare worse than men following aortic heart surgery, study finds
February 15, 2019 - High-protein and low-calorie diet helps older adults lose weight safely, shows study
February 15, 2019 - Drug microdosing effects may not measure up to big expectations
February 15, 2019 - Discharged, Dismissed: ERs Often Miss Chance To Set Overdose Survivors On ‘Better Path’
February 15, 2019 - A digitized lab environment to be showcased at smartLAB 2019
February 15, 2019 - Scientists uncover main mechanisms of fluconazole drug resistance
February 15, 2019 - New study seeks to understand how colibactin causes cancer
February 15, 2019 - Photoacoustic imaging accurately measures the temperature of deep tissues
February 15, 2019 - Large study finds no association between phthalate exposure and breast cancer risk
February 15, 2019 - New research explains presence of ‘natural’ magnetism in human cells
February 15, 2019 - Bio-Rad launches new digital PCR system and kit for monitoring treatment response in CML patients
February 15, 2019 - Excessive daytime sleepiness in OSA patients linked to greater risk for cardiovascular diseases
February 15, 2019 - Scientists shed light on damaging cell effects linked to aging
February 15, 2019 - Celiac disease may be caused by stomach bug in childhood
February 15, 2019 - NHS performance figures highlight the true scale of Emergency Department crisis
February 15, 2019 - High intensity exercise may improve health by increasing gut microbiota diversity
February 15, 2019 - Apellis’ APL-2 Receives Orphan Drug Designation from the FDA for the Treatment of Autoimmune Hemolytic Anemia
February 15, 2019 - Couples creating art or playing board games release ‘love hormone’
February 15, 2019 - Glimpsing The Future At Gargantuan Health Tech Showcase
February 15, 2019 - Common herbicide found to increase the risk of lymphoma
February 15, 2019 - Over-abundance of energy to cells could increase cancer risk
February 15, 2019 - Oxford Genetics appoints Jocelyne Bath as new Chief Operating Officer
February 15, 2019 - Castration-resistant metastatic prostate cancer responds to combination of immune checkpoint inhibitors
February 15, 2019 - Large-scale clinical trial begins to study liver transplantation between people with HIV
February 15, 2019 - Cannabis use among adolescents linked with increased risk of depression in adulthood
February 15, 2019 - Fractures, head injuries common in electric scooter accidents, UCLA study finds
February 15, 2019 - Prenatal maternal depression has important consequences for infant temperament, study shows
February 15, 2019 - Stereotactic body radiotherapy effective in treating men with low- or intermediate-risk prostate cancer
February 15, 2019 - Zogenix Submits New Drug Application to U.S. Food & Drug Administration for Fintepla for the Treatment of Dravet Syndrome
February 15, 2019 - Certain birthmarks warrant quick treatment, pediatricians say
February 15, 2019 - New machine learning method predicts if atypical ductal hyperplasia will turn cancerous
February 15, 2019 - Whole-genome sequencing and sharing real-time data could limit spread of foodborne bacteria
February 15, 2019 - FDA warns doctor for illegally marketing unapproved implantable device
February 15, 2019 - New injury documentation tool may provide better evidence for elder abuse cases
February 15, 2019 - Physiological age is a better predictor of survival than chronological age, shows study
February 15, 2019 - New study reveals high success rate for hip and knee replacements
February 15, 2019 - Prenatal exposures to BPA may pose threat to human ovarian function
February 15, 2019 - Suspicious spots on the lungs of children with rhabdomyosarcoma do not behave like metastases
February 15, 2019 - Diet drinks daily could raise stroke risk says study
February 15, 2019 - Many Systematic Reviews Do Not Fully Report Adverse Events
February 15, 2019 - Seven tips to protect your child from burns
February 15, 2019 - Keynote speakers announced for CBD Expo MIDWEST
Liver immune cells contain inert HIV and are unlikely to reproduce infection, study reveals

Liver immune cells contain inert HIV and are unlikely to reproduce infection, study reveals

image_pdfDownload PDFimage_print

In a proof-of-principle study, researchers at Johns Hopkins revealed that certain immune system cells found in the human liver, called liver macrophages, contain only inert HIV and aren’t likely to reproduce infection on their own in HIV-infected people on long-term antiretroviral therapy (ART). ART is a regimen containing combinations of HIV-targeting drugs that prevents the growth of the virus but does not eradicate it.

The report on the findings, published in the October issue of the Journal of Clinical Investigation, revealed that although inactive, HIV can remain in liver immune cells after more than 10 years of ART. However, the researchers say there is no evidence that it can be considered an HIV reservoir in this state because the virus can’t replicate at high levels.

This revelation supports the idea that when developing HIV treatments, liver macrophages can be ruled out as a cell type that may act as a reservoir of the virus. The researchers argue that it may not be important to address curing liver macrophage infection, thereby narrowing targets for treatment.

“Our study was the first, to our knowledge, that looked at whether liver macrophages also served as reservoirs, similar to CD4+ T cells, in ART-suppressed, HIV-infected people,” says Ashwin Balagopal, M.D., associate professor of medicine in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine and senior author of the study. “We zeroed in on the liver since liver macrophages comprise 80 to 90 percent of all macrophages in the body,” notes Balagopal.

According to the Centers for Disease Control and Prevention, 36.7 million people worldwide and 1.1 million people in the United States are infected with HIV. Commonly, ART is used to suppress the replication of HIV and control the progression of AIDS in humans. The virus infects the body’s immune system–the white blood cells also referred to as T cells and macrophages.

The most common reservoirs in humans are in immune cells called resting memory CD4+ T cells. Even when ART suppresses HIV, the virus can remain hidden in cellular reservoirs. The interruption or discontinuation of ART can spread HIV to new cells because the virus becomes active and begins replicating again.

“Although it is well-established that macrophages are a natural target for HIV infection, for many years researchers have not known whether macrophages also harbor HIV in a reservoir during long-term ART, similar to the resting memory CD4+ T cells,” adds Balagopal.

The inability to wipe out reservoirs of infectious HIV has for decades frustrated efforts to completely cure the infection. In addition, it means that the interruption or discontinuation of ART at any time reactivates HIV replication, spreading the virus to new cells.

Balagopal and his team examined if any HIV reservoirs remained in populations of tissue macrophages that reside in livers; specifically, he looked for latent HIV-1, the most common strain of the virus, in liver macrophages.

“The other organs we could have examined that contain macrophages include the brain, heart, lungs and skin,” says Abraham Kandathil, Ph.D., research associate in the Division of Infectious Diseases at the Johns Hopkins University School of Medicine, who performed all key experiments. “Macrophages can be scarce in these organs in comparison to the liver, and therefore are even more difficult to obtain than liver macrophages in sufficiently large numbers,” concludes Kandathil.

To determine if liver macrophages serve as a reservoir of infection-capable HIV-1 after ART, liver tissue samples were taken from nine HIV-1 infected persons, seven of whom underwent liver transplantation at The Johns Hopkins Hospital and otherwise would have had their livers discarded because they were no longer functional and/or cancerous.

Eight of the nine persons were on ART for periods ranging from eight months to approximately 12 years.

Using lab techniques that separate out the liver macrophages, the researchers found HIV-1 to be present in the macrophages even after exposure to longstanding virus-suppressing ART.

“However, when we tried to simulate virus “rebound” by activating liver macrophages to see if the virus was infectious or noninfectious, we found HIV-1 at low levels, without the ability to replicate at high levels needed to re-establish infection,” says Kandathil.

By examining the virus in these liver samples and separating out the liver macrophages, the researchers found HIV-1 to be present in the macrophages of one person among the group who took suppressive ART for almost 12 years. However, the virus was still determined to be inert, otherwise unable to replicate itself and spread.

The researchers conclude that while liver macrophages might harbor HIV-1 for a long time, it’s unlikely these viruses could continue an infection on their own, and they are unlikely to function as a reservoir because the viruses were not able to replicate.

In the future, Balagopal says, more research is needed to determine if the inert HIV-1 infected liver macrophages have any functional significance in people taking ART because expression of defective HIV-1 proteins can confuse the immune system and cause tissue inflammation.

“While we have potentially ruled out the liver as an infectious reservoir, it’s important to identify all of the relevant virus reservoirs in the body, such as the brain, since it’s likely that the virus hides in the DNA of different cell types and will require different strategies to cure,” says Balagopal. “Then we can move forward to finding a ‘functional’ HIV-1 cure that’s comprehensive.”

The researchers caution that their study is limited because of the small number of liver macrophages and human samples studied. In addition, the small number of CD4+ T cells (less than or equal to 1 percent) in the liver macrophage cultures may affect the researchers’ ability to detect them, although they say it is virtually impossible for contamination of 1 percent or less to have confounded the findings.

Source:

https://www.hopkinsmedicine.org/news/newsroom/news-releases/hiv-in-liver-cells-found-to-be-inactive-narrowing-potential-treatment-targets

Tagged with:

About author

Related Articles