The recent discovery by University of Virginia School of Medicine scientists has brought researchers closer to finding ways to flush out the dormant HIV virus and eliminate it for good. The study reveals a key reason why HIV remains so difficult to cure: subtle variations in the viral control system, known as the Rev-RRE axis, influence how efficiently the virus replicates and how easily it reactivates from latency.

HIV treatment has made remarkable progress, allowing the virus to be suppressed to undetectable levels in the blood. However, the virus never truly goes away; instead, it hides in the body in a dormant or “latent” state, and if medications are ever stopped, it can reemerge. This stealth mode poses one of the biggest challenges to finding a cure.

“The HIV treatment is lifesaving but also lifelong,” said Patrick Jackson, MD, one of the two lead authors on the paper. “Understanding how the virus stays latent in cells could help us develop a lasting cure for HIV.”

UVA’s new findings reveal a critical clue to how HIV controls this hiding act. The research shows that small changes in the Rev-RRE axis regulatory system directly impact HIV’s ability to replicate and emerge from latency. The study found that viruses with low Rev activity had a disadvantage in both replication and latency reactivation.

This variability helps explain why HIV persists despite aggressive treatment. To develop a cure, future therapies may need to account for these subtle variations that allow the virus to shift its behavior, the researchers say.

“Rev has often been overlooked in the context of latency, even though it’s essential for HIV replication,” said Godfrey Dzhivhuho, PhD, the other lead author of the study. “Our work helps explain why some current ‘shock and kill’ approaches struggle to fully reactivate the virus.”

If a portion of the viral reservoir has low Rev-RRE activity, it will be more resistant to reactivation. By enhancing the Rev-RRE axis, we may be able to induce a stronger and more complete latency reversal and bring us closer to strategies that can truly clear the virus.

The researchers hope this work brings them one step closer to a cure, not just by uncovering how the virus works, but by helping design smarter strategies to finally eliminate it. That’s what drives them every day in this research.

This work was supported by the Myles H. Thaler Research Support Gift to UVA and by the National Institutes of Health, grants R21 AI134208 and K08 AI136671.

The plague, caused by the bacterium Yersinia pestis, has been a persistent threat to human populations for centuries. A recent study published in the journal Science sheds light on how a single gene in the bacterium allowed it to adapt and survive for hundreds of years. The research, conducted by scientists at McMaster University and France’s Institut Pasteur, reveals that changes in the copy number of the pla gene led to a reduction in virulence and an increase in the length of time it took to kill its victims.

The study examines the evolution of the plague during three major pandemics: the Plague of Justinian, the Black Death, and the third plague pandemic. The researchers found that strains of the Justinian plague became extinct after 300 years of ravaging European and Middle Eastern populations. Strains of the second pandemic emerged from infected rodent populations, causing the Black Death, before breaking into two major lineages.

One lineage is the ancestor of all present-day strains, while the other re-emerged over centuries in Europe and ultimately went extinct by the early 19th century. The researchers used hundreds of samples from ancient and modern plague victims to screen for the pla gene and perform extensive genetic analysis.

Their findings suggest that a reduction in the copy number of the pla gene led to a decrease in virulence and an increase in the length of time it took to kill its hosts. In mice models of bubonic plague, this change resulted in a 20% reduction in mortality and increased the length of infection, allowing the hosts to live longer before dying.

The scientists also identified a striking similarity between the trajectories of modern and ancient strains, which independently evolved similar reductions in pla in the later stages of the first and second pandemic. This suggests that when the gene copy number dropped, the infected rats lived longer, spreading the infection farther and ensuring the reproductive success of the pathogen.

The researchers propose that this evolutionary change may reflect the changing size and density of rodent and human populations. They also found three contemporary strains with pla depletion in a collection at the Institut Pasteur.

This study provides valuable insights into the evolution of the plague and its impact on human history. It highlights the importance of understanding the complex relationships between pathogens, their hosts, and their environments, as well as the need for continued research into the causes and consequences of pandemics.

The findings also underscore the ongoing threat posed by the plague in regions like Madagascar and the Democratic Republic of Congo, where cases are regularly reported.

Overall, this study sheds new light on the evolution of a single gene that allowed the plague to adapt and survive for centuries. It emphasizes the importance of continued research into the causes and consequences of pandemics and highlights the need for effective strategies to combat infectious diseases that continue to pose significant threats to global health.

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Ancient Arctic Nursery: 73 Million-Year-Old Bird Fossils Discovered in Alaska

For half of the time birds have existed on Earth – a staggering 150 million years – they’ve been nesting in the Arctic, according to a groundbreaking paper featured in Science. The study reveals that millions of birds gathered in the polar regions 73 million years ago, raising their young amidst dinosaurs and other prehistoric creatures.

The research, led by Lauren Wilson from Princeton University, is based on dozens of tiny fossilized bones and teeth found at an Alaska excavation site. These ancient bird fossils, which include diving birds resembling loons, gull-like birds, and various types of ducks and geese, push back the record of birds breeding in the polar regions by 25 to 30 million years.

Prior to this study, the earliest known evidence of birds reproducing in either the Arctic or Antarctic was about 47 million years ago. This new discovery sheds light on the evolution of modern bird species and highlights the importance of the Arctic as a nursery for these animals.

The fossil collection is part of the University of Alaska Museum of the North’s collections, and the research team used an uncommon excavation and analysis approach to recover the tiny bones and teeth. By examining every bone and tooth they could find, from the visible to the microscopic, the scientists were able to identify multiple types of birds that coexisted with dinosaurs in the Arctic.

This study has significant implications for our understanding of bird evolution and the behavior of ancient species. As Pat Druckenmiller, senior author of the paper and director of the University of Alaska Museum of the North, notes, “The Arctic is considered the nursery for modern birds. It’s kind of cool when you go to Creamer’s Field [a Fairbanks-area stopover for migrating geese, ducks, and cranes] to know that they have been doing this for 73 million years.”

While further research is needed to confirm whether these ancient bird fossils belong to the Neornithes group (which includes all modern birds), this study has already pushed back the record of birds breeding in the polar regions by millions of years. The findings are a testament to the value of an uncommon approach to fossil hunting and highlight the importance of continued research into the evolution and behavior of ancient species.