A multinational team led by Weill Cornell Medicine investigators developed a test that will help measure the persistence of HIV in people affected by viral strains found predominantly in Africa—a vital tool in the search for an HIV cure that will benefit patients around the world.
The study, published in Nature Communications on July 2, helps fill a major gap in human immunodeficiency virus (HIV) research. Most HIV studies have focused on strains circulating in Western countries, predominantly in men who have sex with men affected by subtype B. Few studies have examined strains circulating in Africa, where women are disproportionately affected.
“HIV cure research tends to focus on viral strains circulating in developed countries, but to achieve a cure that is globally applicable, we must study viral strains that are affecting other regions of the world,” said lead author Dr. Guinevere Lee, assistant professor of virology in medicine in the Division of Infectious Diseases and assistant professor of microbiology and immunology at Weill Cornell Medicine.
The findings show—like other studies in developed countries—that HIV strains circulating in Africa establish viral reservoirs in the human body. Although antiretroviral therapy can reduce the level of HIV in the blood to an undetectable level, these dormant reservoirs continue to survive.
They contain a large number of defective proviral DNA genomes which can’t produce new infectious viruses, but a small number of genomes remain genetically intact and ready to produce active viruses if antiretroviral treatment is interrupted.
The large proportion of defective viral genomes obscures researchers’ attempts to accurately quantify the copies of intact proviruses.
“We are looking for a needle in a haystack: To achieve an HIV cure, we need to first find out whether any genome-intact proviruses remain in the body during antiretroviral treatment. Our new assay allows us to do this. Then we need to target and eliminate the intact proviral DNA capable of producing new viruses,” Dr. Lee explained.
Broadening the lens of HIV research with a new assay
Dr. Lee and her colleagues analyzed DNA from immune cells called CD4+ T cells, where viral DNA hides, of 16 women and seven men receiving antiretroviral HIV treatment in Uganda. Genetic sequencing of the virus revealed two predominant HIV-1 subtypes: A1 and D (a notoriously aggressive strain). The study also identified viral hybrids of A1 and D.
The team then modified existing laboratory tests that identify HIV subtype B proviruses to detect proviruses that are subtypes A1 and D. “The new assay we’ve developed will help researchers home in on the intact proviral genomes relevant to HIV cure research for patients affected by these under studied strains,” Dr. Lee said.
Dr. Lee and her multinational, multi-institution collaborators are already using the new assay to study long-term viral persistence in Uganda. Their findings show that the composition of the HIV proviral genomic landscape is broadly comparable between subtypes A1, D and B suggesting that approaches to target intact HIV reservoirs in Africa will face similar “needle-in-a-haystack” challenges as in North America and Europe.
Future studies will also need to evaluate differences in non-B subtypes to understand whether subtype-specific factors impact persistence, reactivation or clearance in viral reservoirs.
Researchers from Simon Fraser University, Canada; British Columbia Center for Excellence in HIV/AIDS, Canada; Rakai Health Sciences Program, Uganda; University of Cape Town, South Africa; and Johns Hopkins University School of Medicine also contributed to this study.
More information: Lee, G.Q., et al. HIV-1 subtype A1, D, and recombinant proviral genome landscapes during long-term suppressive therapy. Nature Communications (2024). DOI: 10.1038/s41467-024-48985-9
News
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
Tiny Metal Nanodots Obliterate Cancer Cells While Largely Sparing Healthy Tissue
Scientists have developed tiny metal-oxide particles that push cancer cells past their stress limits while sparing healthy tissue. An international team led by RMIT University has developed tiny particles called nanodots, crafted from a metallic compound, [...]
Gold Nanoclusters Could Supercharge Quantum Computers
Researchers found that gold “super atoms” can behave like the atoms in top-tier quantum systems—only far easier to scale. These tiny clusters can be customized at the molecular level, offering a powerful, tunable foundation [...]
A single shot of HPV vaccine may be enough to fight cervical cancer, study finds
WASHINGTON -- A single HPV vaccination appears just as effective as two doses at preventing the viral infection that causes cervical cancer, researchers reported Wednesday. HPV, or human papillomavirus, is very common and spread [...]
New technique overcomes technological barrier in 3D brain imaging
Scientists at the Swiss Light Source SLS have succeeded in mapping a piece of brain tissue in 3D at unprecedented resolution using X-rays, non-destructively. The breakthrough overcomes a long-standing technological barrier that had limited [...]
Scientists Uncover Hidden Blood Pattern in Long COVID
Researchers found persistent microclot and NET structures in Long COVID blood that may explain long-lasting symptoms. Researchers examining Long COVID have identified a structural connection between circulating microclots and neutrophil extracellular traps (NETs). The [...]
This Cellular Trick Helps Cancer Spread, but Could Also Stop It
Groups of normal cbiells can sense far into their surroundings, helping explain cancer cell migration. Understanding this ability could lead to new ways to limit tumor spread. The tale of the princess and the [...]
New mRNA therapy targets drug-resistant pneumonia
Bacteria that multiply on surfaces are a major headache in health care when they gain a foothold on, for example, implants or in catheters. Researchers at Chalmers University of Technology in Sweden have found [...]
Current Heart Health Guidelines Are Failing To Catch a Deadly Genetic Killer
New research reveals that standard screening misses most people with a common inherited cholesterol disorder. A Mayo Clinic study reports that current genetic screening guidelines overlook most people who have familial hypercholesterolemia, an inherited disorder that [...]
Scientists Identify the Evolutionary “Purpose” of Consciousness
Summary: Researchers at Ruhr University Bochum explore why consciousness evolved and why different species developed it in distinct ways. By comparing humans with birds, they show that complex awareness may arise through different neural architectures yet [...]
Novel mRNA therapy curbs antibiotic-resistant infections in preclinical lung models
Researchers at the Icahn School of Medicine at Mount Sinai and collaborators have reported early success with a novel mRNA-based therapy designed to combat antibiotic-resistant bacteria. The findings, published in Nature Biotechnology, show that in [...]
