Breaking News
February 20, 2019 - Over Half of Hip Replacements Expected to Last 25 Years
February 20, 2019 - Microscopic eye movements affect how we see contrast
February 20, 2019 - Computer vs. patient: Fighting for residents’ attention | News Center
February 20, 2019 - New “Smart Drug” Shows Promise for Metastatic Triple-Negative Breast Cancer
February 20, 2019 - Researchers develop large-scale window material for high-efficiency PM2.5 capture
February 20, 2019 - Widespread confusion among consumers on food date labels lead to unnecessary discards
February 20, 2019 - Researchers unlock plant’s secret of producing specialized metabolites
February 20, 2019 - Newly released national framework identifies obstacles to improving EMS systems
February 20, 2019 - Exercise can shift human body clock depending on time when people work out
February 20, 2019 - Female adolescent blood donors more likely to have iron deficiency and related anemia
February 20, 2019 - Rubicon level linked to inhibition of autophagic process
February 20, 2019 - Researchers find potential therapeutic strategy to treat Alzheimer’s
February 20, 2019 - New forms of older anti-cancer agent appear to enhance immune response to fight melanoma
February 20, 2019 - Health Tip: Eat Less Saturated Fat
February 20, 2019 - Sleeping in contact lenses puts you at risk of dangerous infection
February 20, 2019 - “We should study that!”: How a nurse-scientist found her passion
February 20, 2019 - Cervical microbiome may influence HPV infection more than previously thought
February 20, 2019 - Sausage mislabeling in Canada is down, new study finds
February 20, 2019 - Study shows blood pressure benefits of morning exercise for older overweight/obese adults
February 20, 2019 - New screening method could catch organ rejection much earlier without a biopsy needle
February 20, 2019 - Study may have important implications for refining parenting during child’s adolescence
February 20, 2019 - Study sheds new light on how antibiotic resistance genes are transferred between bacteria
February 20, 2019 - Chronic Wasting Disease may soon spread to humans, warns CDC
February 20, 2019 - Scientists identify new genetic causes linked to abnormal pregnancies and miscarriages
February 20, 2019 - Using LyoSpeed technology to avoid residual solvent when drying HPLC fractions
February 20, 2019 - Scientists join forces to identify a new approach to fight African sleeping sickness
February 20, 2019 - New screening tool more likely to identify sexual and labor exploitation of youth
February 20, 2019 - Newly licensed nurses work for long hours, also have a second paid job
February 20, 2019 - Physicists identify simple mechanism used by deadly bacteria to fend off antibiotics
February 20, 2019 - FDA Grants Priority Review to Genentech’s Personalized Medicine Entrectinib
February 20, 2019 - Exposure to chemicals before and after birth is associated with a decrease in lung function
February 20, 2019 - Neuroscientists reveal that simple brain region can guide complex feats of mental activity
February 20, 2019 - Study finds new link between food allergies and multiple sclerosis
February 20, 2019 - First gene therapy operation for macular degeneration is a success
February 20, 2019 - Physicians graduated outside the U.S. offer better care for Medicare patients with complex needs
February 20, 2019 - Study shows therapeutic potential of VEGF-A mRNA for regenerative angiogenesis in humans
February 20, 2019 - FDA Approves Keytruda (pembrolizumab) for the Adjuvant Treatment of Patients with Melanoma with Involvement of Lymph Node(s) Following Complete Resection
February 20, 2019 - Study identifies brain cells that modulate behavioral response to threats
February 20, 2019 - Researchers take closer look at how viruses bind cells and cause infection
February 20, 2019 - Newly developed gene therapy helps decelerate aging process
February 20, 2019 - Study suggests new treatment strategy for deadly brain cancer
February 20, 2019 - Scientists develop unique hybrid implant that imitates bone structure
February 20, 2019 - Push-ups can be tailored to meet specific needs of individuals
February 20, 2019 - Early-career job loss has long term health implications
February 20, 2019 - CVD Does Not Modify Depression-Mortality Link in Elderly
February 20, 2019 - Electrical activity early in fruit flies’ brain development could shed light on how neurons wire the brain
February 20, 2019 - Machine learning technique helps predict which asthma patients respond to corticosteroid therapy
February 20, 2019 - Self-reported sleep duration is a useful tool to measure sleep in children, study suggests
February 20, 2019 - T-cells play key role in how the body fights follicular lymphoma
February 20, 2019 - Study shows how 3D organization of genetic material helps perpetuate the species
February 20, 2019 - Researchers engineer stem cell with ‘suicide genes’ to induce cell death in all but beta cells
February 20, 2019 - Study reveals major sex differences in management of cardiovascular risk factors among U.S. adults
February 20, 2019 - Health Tip: Get Your Child to School on Time
February 20, 2019 - Shortcut strategy for screening compounds with clinical potentials for drug development
February 20, 2019 - Common acid reflux drugs tied to elevated risk for kidney disease
February 20, 2019 - Microbiome could be culprit when good drugs do harm
February 20, 2019 - Prenatal exposure to forest fires causes stunted growth in children
February 20, 2019 - Gene therapy restores hearing in mice with congenital genetic deafness
February 20, 2019 - First molecular test predicts treatment response for kidney cancer
February 20, 2019 - New method for improved visualization of single-cell RNA- sequencing data
February 20, 2019 - Researchers capture altered brain activity patterns of Parkinson’s in mice
February 20, 2019 - A possible blood test for detecting Alzheimer’s disease before symptoms show
February 20, 2019 - Primary care physicians associated with longevity, new research finds
February 19, 2019 - New study identifies many key lessons to establish sanctioned safe consumption sites
February 19, 2019 - Single CRISPR treatment can safely and stably correct genetic disease
February 19, 2019 - Multinational initiative to study familial primary distal renal tubular acidosis
February 19, 2019 - Breakthrough study highlights the promise of cell therapies for muscular dystrophy
February 19, 2019 - Subsymptom Threshold Exercise Speeds Concussion Recovery
February 19, 2019 - Midline venous catheters – infants: MedlinePlus Medical Encyclopedia
February 19, 2019 - Searching for side effects
February 19, 2019 - Humanity is all right, probably, although human extinction remains quite possible, researcher says
February 19, 2019 - Having Anesthesia Once as a Baby Does Not Cause Learning Disabilities, New Research Shows
February 19, 2019 - Anti-cancer immunotherapy could be used to fight HIV
February 19, 2019 - Customized Micropatterning for Improved Physiological Relevance
February 19, 2019 - Unique gene therapy approach paves new way to tackle rare, inherited diseases
February 19, 2019 - Activating gene that helps excite neurons reverses depression in male mice
February 19, 2019 - Science Puzzling Out Differences in Gut Bacteria Around the World
February 19, 2019 - Cells that destroy the intestine
February 19, 2019 - On recovery, vulnerability and ritual: An exhibit in white
February 19, 2019 - Scientific Duo Gets Back To Basics To Make Childbirth Safer
Discovery of how HIV hedges its bets opens the door to new therapies

Discovery of how HIV hedges its bets opens the door to new therapies

image_pdfDownload PDFimage_print
Credit: CC0 Public Domain

A stem cell is one with infinite possibilities. So, for decades, scientists have puzzled over how the cell chooses to keep being a stem cell and continue dividing, or specialize into a specific cell type, like a heart or brain cell.

The same type of decision is made by HIV. When the virus infects a cell, it can either turn on and start multiplying, or turn off so it can hide in the cell until a later date.

“Biology can hedge its bets in a similar way to how you might diversify financial investments,” explained Leor S. Weinberger, Ph.D., the William and Ute Bowes Distinguished Professor and director of the Center for Cell Circuitry at the Gladstone Institutes. “Diversifying investments by placing some funds in high-risk, high-yield stocks and others in low-risk, low-yield savings accounts helps protect against volatility in the market. Similarly, HIV covers its bases in a volatile environment by generating both active and dormant infections.”

But if HIV is randomly switching between these two fates, how does it ever commit to remaining in one state? Weinberger’s laboratory has now answered this longstanding question and potentially uncovered how biological systems make such decisions. Their findings are published today in the prominent scientific journal Cell.

The Virus Rigs the System to Its Advantage

HIV benefits from maintaining both an active state and a dormant, or latent, state.

The active state allows the virus to spread and infect more cells, whereas virus in the latent state can survive in hiding for long periods of time. While the active virus can be killed by antiviral drugs, latent virus lies in wait and can rapidly reactivate when drugs are stopped. Because the latent virus cannot be treated by current therapies, it represents the main obstacle to curing HIV.

Weinberger’s team previously showed that HIV generates these two categories of infection by exploiting random fluctuations in gene expression.

“Even when two cells are genetically identical, one can produce a large amount of a protein, while the other can produce a much smaller amount,” said Maike Hansen, postdoctoral scholar in Weinberger’s laboratory and one of the first authors of the study. “These random fluctuations, called noise, can determine the fate and function of the cell. HIV uses noise to create both active and latent virus.”

To express its genes, HIV uses a mechanism known as alternative splicing, which essentially allows the virus to cut up parts of its genome and arrange them in different combinations. By observing individual cells over time, the researchers discovered that HIV hijacks an exotic form of splicing to tune random noise. This tuning of noise dictates whether the virus will remain stably active or latent.

“We found that HIV uses a particularly inefficient form of splicing to control noise,” added Hansen. “Surprisingly, if it worked efficiently, this mechanism would produce much less active virus. But, by seemingly wasting energy through an inefficient process, HIV can actually better control its decision to remain active.”

Weinberger’s team used a combination of mathematical modeling, imaging, and genetics to show that this type of alternative splicing occurs after transcription, during which genetic information in DNA is copied into a molecule called RNA. Previously, scientists thought that splicing occurred at the same time as transcription. This study represents the first function for post-transcriptional splicing.

Unexplored Targets for HIV Cure Strategies

The study demonstrates that HIV conserved a highly inefficient process on purpose, and by correcting it, scientists could significantly harm the virus. These findings could reveal unexplored targets for the development of novel HIV cure strategies.

“The splicing circuit may give us an opportunity to therapeutically attack the virus in a different way,” said Weinberger, who is also a professor of pharmaceutical chemistry at UC San Francisco. “For a while, there have been proposals to ‘lock’ HIV in latency and ‘block’ it from reactivating, but how to do this wasn’t clear.”

Researchers may now be able to continually force HIV back into latency by exploiting the virus’s splicing circuit and achieve the “lock and block” therapy.

By revealing a new fundamental mechanism, this study also has broader implications in biology. Inefficient splicing likely occurs in 10-20 percent of genes. So, this circuitry may be generally employed to minimize random fluctuations in gene expression and could explain how other biological decisions are stabilized.

The paper “A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization” was published by Cell on May 10, 2018.


Explore further:
Study challenges ‘shock and kill’ approach to eliminating HIV

More information:
Maike M.K. Hansen et al. A Post-Transcriptional Feedback Mechanism for Noise Suppression and Fate Stabilization, Cell (2018). DOI: 10.1016/j.cell.2018.04.005

Journal reference:
Cell

Provided by:
Gladstone Institutes

Tagged with:

About author

Related Articles