Imagine a silent threat lurking within, a fire waiting to be rekindled. That’s the reality for individuals living with HIV. This persistent virus, much like a wildfire, can wreak havoc on the immune system, leaving it vulnerable to infections and diseases. HIV targets and destroys CD4+ T cells, the very orchestrators of our immune defenses. But here’s where it gets controversial… even with effective treatment, the fire isn’t entirely extinguished. Antiretroviral therapy (ART) acts as a crucial fire suppressant, protecting healthy cells from infection. However, it doesn’t eliminate the cells already harboring the virus. These cells, known as latently infected cells, can harbor the virus for years, potentially reactivating and causing viral rebound if treatment is stopped. This means people with HIV must adhere to lifelong ART to prevent the virus from resurfacing and causing further damage to their immune systems.
Researchers at the Cohn lab, affiliated with the Vaccine and Infectious Disease Division, are dedicated to understanding these latent cells and how the immune system interacts with them. Their goal? To uncover potential strategies for an HIV cure. In a recent study published in The Journal of Infectious Diseases, the team investigated the immune response during viral rebound in individuals who paused their ART treatment. The study’s lead researcher, Anna Farrell-Sherman, highlighted the complexity of this immune response: “We don’t understand how the immune system responds to this pathogen that it’s seen fairly frequently at very low levels for perhaps decades but hasn’t had to directly tackle in a very long time.” This unique scenario raises critical questions: What parts of the immune system detect the returning virus? How do they react?
To address these questions, the team closely monitored the immune function of individuals living with HIV during a controlled treatment interruption. Participants temporarily stopped ART while under close medical supervision. All participants experienced a brief HIV rebound before restarting ART. The researchers meticulously analyzed blood samples collected throughout the process, measuring RNA and protein expression across various immune cell types to identify changes in immune activity.
The study yielded a fascinating discovery: in all 10 participants evaluated, a specific type of immune cell, CD16+ monocytes, increased in abundance before the standard clinical tests could detect viral rebound. Think of monocytes as the early warning system of the immune system. They are innate immune cells, meaning they recognize and attack pathogens in general. They play a crucial role in killing invading pathogens and communicating with other immune cells about the infection. CD16+ monocytes, also known as non-classical monocytes, specialize in surveillance of pathogens and production of antiviral signals. The increase of CD16+ monocytes early in HIV rebound may speed up viral detection throughout the body and amplify the signals alerting other immune cells to the virus.
Furthermore, the study revealed that CD16+ monocytes not only increased in number but also heightened their expression of genes that promote inflammation and antiviral activity. This suggests that these cells are actively detecting and suppressing the rebounding virus before it becomes clinically apparent. They’re the first line of defense, the first to react to the ‘smoke’ of the reactivating virus.
This finding is a significant step forward in HIV immunology. As Farrell-Sherman noted, “Monocytes in general are not well studied in the context of HIV and AIDS.” The results highlight the need for further investigation into the role of these cells in controlling the virus.
Looking ahead, the Cohn lab is exploring whether CD16+ monocytes contribute to the immune system’s ability to control latently infected cells. And this is the part most people miss… In a small number of individuals, the immune system can naturally suppress HIV to very low levels without treatment. “We know that some people can live without taking ART and control their own virus, and if we can figure out how and why, we can help more people do that,” Farrell-Sherman shared.
This research was supported by the National Institute of Allergy and Infectious Disease and the Bill and Melinda Gates Foundation.
What are your thoughts on this research? Do you think focusing on the early responders in the immune system is a promising avenue for HIV cure research? Share your opinions in the comments below!