Breaking News
February 18, 2019 - New dental adhesive prevents tooth decay around orthodontic brackets
February 18, 2019 - New eHealth tool shows potential to improve quality of asthma care
February 18, 2019 - New Australian initiative helps emergency clinicians to improve patient care
February 17, 2019 - Apellis Pharmaceuticals’ APL-2 Receives Fast Track Designation from the FDA for the Treatment of Patients with Paroxysmal Nocturnal Hemoglobinuria
February 17, 2019 - Researchers identify faulty ‘brake’ that interferes with heart muscle’s ability to contract and relax
February 17, 2019 - Support from trusted adults can reduce risk of dying in suicidal teens, finds study
February 17, 2019 - Heart attack awareness improved since 2008
February 17, 2019 - Exercise gives a better brain boost to older men than women
February 17, 2019 - New research disproves previous assumptions of how looks influence personality
February 17, 2019 - Cannabis use as a teenager linked to depression later in life
February 17, 2019 - Sinks by Toilets in ICU Patient Rooms Harbor Harmful Bacteria
February 17, 2019 - Cancer cells’ plasticity makes them harder to stop
February 17, 2019 - Young cannabis users have increased risk of depression and suicidal behavior
February 17, 2019 - Tasmanian Devils Likely to Survive Cancer Scourge
February 17, 2019 - Neoadjuvant PD-1 blockade seems effective in glioblastoma
February 17, 2019 - Personal, social factors play role in enabling sustainable return to work after ill health
February 17, 2019 - Mouse studies show ‘inhibition’ theory of autism wrong
February 17, 2019 - Study shows how neuroactive steroids inhibit activity of pro-inflammatory proteins
February 17, 2019 - Use of liver grafts from older donors decreased despite better outcomes in recipients
February 17, 2019 - MUSC researchers discover new mechanism for a class of anti-cancer drugs
February 17, 2019 - HPV misconceptions are causing women to miss smear tests
February 17, 2019 - Sanofi and Regeneron Offer Praluent (alirocumab) at a New Reduced U.S. List Price
February 17, 2019 - Researchers say auditory testing can identify children for autism screening
February 17, 2019 - New method analyzes how single biological cells react to stressful situations
February 17, 2019 - WVU gynecologic oncologist investigates novel treatment for cervical and vaginal cancers
February 17, 2019 - ADHD diagnoses poorly documented
February 17, 2019 - Majority of gender minority youth do not identify with traditional sexual identity labels
February 17, 2019 - AbbVie, Teneobio enter into strategic transaction to develop potential treatment for multiple myeloma
February 17, 2019 - Lower Birth Weight May Up Risk for Psychiatric Disorders
February 17, 2019 - Scientists identify reversible molecular defect underlying rheumatoid arthritis
February 17, 2019 - Moffitt researchers shed light on how CAR T cells function mechanistically
February 16, 2019 - Female Anatomy May Play Big Role in Sperm’s Success
February 16, 2019 - BMI may mediate inverse link between fiber intake, knee OA
February 16, 2019 - Movement impairments in autism can be reversed through behavioral training
February 16, 2019 - Studies address racial disparities in postpartum period and cardiovascular health
February 16, 2019 - Scientists implicate hidden genes in the severity of autism symptoms
February 16, 2019 - Decreased deep sleep linked to early signs of Alzheimer’s disease
February 16, 2019 - Neuroscientists show how the brain responds to texture
February 16, 2019 - Gilead Announces Topline Data From Phase 3 STELLAR-4 Study of Selonsertib in Compensated Cirrhosis (F4) Due to Nonalcoholic Steatohepatitis (NASH)
February 16, 2019 - What Can I Do About Sweating? (for Teens)
February 16, 2019 - Companies navigate dementia conversations with older workers
February 16, 2019 - Newly developed stem cell technologies show promise for treating PD patients
February 16, 2019 - Collaborative material research could advance self-assembling nanomaterials
February 16, 2019 - Researchers take major step in creating technology that mimics the human brain
February 16, 2019 - Erasing memories associated with cocaine use reduces drug seeking behavior
February 16, 2019 - Artificial intelligence can accurately predict prognosis of ovarian cancer patients
February 16, 2019 - Racial disparities in cancer deaths on the decline for America
February 16, 2019 - FDA authorizes new interoperable insulin pump for children, adults with diabetes
February 16, 2019 - Coexisting Medical Conditions, Smoking Explain PTSD-CVD Link
February 16, 2019 - Skin Cancer Screening: MedlinePlus Lab Test Information
February 16, 2019 - ‘Happiness’ exercises can boost mood in those recovering from substance use disorder
February 16, 2019 - Cell manipulation could soon halt or reverse aging
February 16, 2019 - Pumped Breast Milk Falls Short of Breastfed Version
February 16, 2019 - Men’s porn habits could fuel partners’ eating disorders, study suggests
February 16, 2019 - Rapid progression of age-related diseases may result from formation of vicious cycles
February 16, 2019 - Immune checkpoint molecule protects against future development of cancer
February 16, 2019 - New method produces hydrogels that have properties similar to cells’ environment
February 16, 2019 - $4.1 million funding for heart research on Valentine’s Day
February 16, 2019 - General anesthesia in early infancy unlikely to have lasting effects on developing brains
February 16, 2019 - New breakthroughs for muscular dystrophy research
February 16, 2019 - First Opinion: Embryo editing for higher IQ is a fantasy. Embryo profiling for it is almost here
February 16, 2019 - Vapers develop cancer-related gene deregulation as cigarette smokers
February 16, 2019 - Bringing Antimicrobial Susceptibility Testing (AST) to the Community
February 16, 2019 - Decolonization protocol after hospital discharge can prevent dangerous infections
February 16, 2019 - Children with ASD more likely to face maltreatment, study finds
February 16, 2019 - Study finds genetic vulnerability to use of menthol cigarettes
February 16, 2019 - Promising drug developed to rejuvenate muscle cells
February 16, 2019 - H-RT should be the standard of care for men with low risk prostate cancer, study shows
February 16, 2019 - New technique using patients’ own modified cells could help treat Crohn’s disease
February 16, 2019 - Therapeutic endoscopy has an expanding role in the treatment of IBD
February 16, 2019 - Blood clot discovery could lead to development of better treatments for blood diseases
February 16, 2019 - Intervention can increase exclusive breastfeeding rates
February 16, 2019 - New project explores how gaming technologies can help cancer patients communicate better
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
HIV begins to yield secrets of how it hides in cells

HIV begins to yield secrets of how it hides in cells

image_pdfDownload PDFimage_print
Credit: CC0 Public Domain

UC San Francisco scientists have uncovered new mechanisms by which HIV hides in infected cells, resting in a latent state that evades the body’s immune system and prevents antiviral drugs from flushing it out.

The findings, published online February 28, 2018, in Science Translational Medicine, could help scientists design and test new therapies aimed at curing a virus that still affects more than 1 million Americans.

Typically, HIV commandeers immune system cells called CD4 T cells and turns them into factories that can produce more virus. But for reasons that remain mysterious, a tiny fraction of these infected cells become dormant and do not make virus. Finding these “silent” HIV-infected cells is extremely challenging.

“We can’t even separate out uninfected from infected cells, let alone latently infected cells,” said Steven A. Yukl, MD, associate professor of medicine at UCSF and a staff physician at the San Francisco Veterans Affairs Medical Center. “Latently infected cells are extremely rare—one in 1 million CD4 T cells—and we don’t know how to identify them.”

Latently infected cells can remain dormant for decades—perhaps indefinitely—before encountering certain natural stimuli that cause them to start producing viral particles. Current antiretroviral therapies (ARTs) cannot kill latently infected cells, nor can they prevent them from reactivating. At best, ARTs can keep the virus at bay, but it usually rebounds as soon as patients stop taking the drugs.

“Knowing what mechanisms keep these latently infected cells silent would help us develop a therapy to either wake them up and kill them or silence them permanently,” Yukl said. “Until we figure out what keeps them latent, we can’t cure HIV.”

Scientists at the UCSF-affiliated Gladstone Institutes had previously developed a device that could track HIV inside cloned laboratory CD4 cells, allowing them to scrutinize the entire course of an HIV infection, including the latency stage. But, since laboratory systems do not necessarily show what is really happening inside a human body, Yukl’s team set out to examine cells taken from 18 HIV-infected patients.

Previously, researchers thought that latency stemmed from CD4 cells’ inability to convert HIV DNA into viral RNA. It was thought that some unknown cellular mechanism was blocking the start of this DNA-to-RNA conversion process, called transcription, which meant that while the viral DNA persisted, it was never translated into viral proteins that would trigger a response from the body’s immune system.

Yukl and his colleagues discovered that this wasn’t the case. Using a panel of tests for different regions of the viral RNA (based on an amplification and quantification method called droplet digital PCR), the team detected multiple fragments of viral RNA, meaning that the process of converting the viral DNA to RNA was at least starting in latently infected cells.

These RNA fragments were almost all short or incomplete, however, which meant that the transcription process was stalling out at various stages. Infected cells were unable to make longer, full-length, or spliced viral RNAs, and the transcription process was never completed. These problems with transcription were reversed, however, when researchers activated the infected T cells.

“It’s not that the cells aren’t making viral RNA, but that the RNA isn’t finished,” Yukl said. To wake up latent cells, he added, the full viral transcription process needs to take place, and none of the currently available drugs can effectively complete this process. “Now we can start developing drugs that will make them finish the viral RNA, which can then be made into viral proteins so that the body can recognize and kill the infected cells.”

Researchers have experimented with various ‘latency-reversing’ agents, although they are not yet used in the clinic. In the new study, the researchers discovered that each of these agents helped the cells at different steps along the process of making viral RNA, so a combination of them may be needed to completely activate the CD4 cells from their latent state.

“One of the nice things about knowing all these mechanisms is that we can look for new drugs or combinations and test how well they can overcome these transcription blocks,” Yukl said. “It provides a roadmap to design and evaluate new therapies.”


Explore further:
Using viruses to fight viruses: New approach eliminates ‘dormant’ HIV-infected cells

More information:
Steven A. Yukl et al. HIV latency in isolated patient CD4 + T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing, Science Translational Medicine (2018). DOI: 10.1126/scitranslmed.aap9927

Journal reference:
Science Translational Medicine

Provided by:
University of California, San Francisco

Tagged with:

About author

Related Articles