Understanding how HIV, Kaposi’s sarcoma herpesvirus and hepatitis C virus interact to influence cancer risk
Researchers from the University of California have explored how immune system dysfunction linked to Kaposi’s sarcoma-associated herpesvirus (KSHV) — the virus commonly tied to Kaposi’s sarcoma — can drive cancer development in people who are also living with HIV. The new findings, which shed light on the biological pathway behind this risk, were detailed in the journal PLOS Pathogens.
For years, clinicians have recognized that co-infections can complicate the clinical picture for individuals with HIV. In particular, hepatitis C virus (HCV) has been associated with an increased cancer risk in people who are HIV-positive. While the exact mechanism remained unclear, researchers hypothesized that the immune system’s response to these infections could become dysregulated, leading to chronic inflammation and opportunities for cancerous changes. The latest study advances this understanding by applying modern laboratory techniques to map the immune alterations that occur when these pathogens intersect.
The investigative team employed a combination of sophisticated cell sequencing, mass cytometry, and a herpesvirus model to simulate and study the immune system’s behavior in the presence of both HIV and KSHV. These methods allowed the scientists to observe how immune cells respond at the single-cell level, revealing shifts in the activity and function of key cellular players in the immune network.
A central finding is that HCV infection can influence monocytes, a type of white blood cell that patrols the bloodstream and tissues. When these monocytes encounter HCV, they can differentiate into macrophages, cells whose primary job is to engulf and digest bacteria, dead cells, and other foreign particles. However, the study showed that these macrophages, shaped by the viral environment, may become less effective at presenting antigens to T cells — the immune cells that coordinate targeted responses against infected or cancerous cells.
With macrophages less capable of properly engaging T cells, the overall T-cell activation diminishes. This reduction in T-cell vigor weakens the body’s surveillance against abnormal cells that could transform into cancer. The resulting state of immune dysfunction fosters a pro-inflammatory milieu. Chronic inflammation is a well-known driver of genomic instability and tumor progression, creating an environment where cancer cells can emerge and grow more easily.
The researchers emphasize that this cascade does not arise from a single faulty step but from a network of interactions among HIV, KSHV, and HCV that collectively reshape immune responses. The altered signaling and cell-to-cell communication observed in the study help explain why co-infection with these viruses may carry a higher cancer risk than infection with any one virus alone. In practical terms, this work points to potential biomarkers that could identify individuals at greater risk and to avenues for therapeutic strategies aimed at restoring proper T-cell activation and macrophage function in affected populations.
From a clinical perspective, these results underscore the importance of comprehensive infection management in people living with HIV. Regular monitoring for liver disease and hepatitis C co-infection remains crucial, as does attention to conditions associated with KSHV. By better understanding how these pathogens disrupt immune balance, clinicians can tailor interventions to reduce inflammation and bolster immune-mediated cancer surveillance. In the larger scope of HIV care, the study contributes to a growing body of evidence that immune health is central to preventing infections from escalating into malignancy.
Overall, the UC-led research reveals a cohesive narrative: viral interactions shape immune cell behavior in a way that can undermine cancer defenses. The work demonstrates how modern immunology tools can illuminate complex disease processes and points toward strategies that might mitigate cancer risk for patients facing multiple viral infections. The findings add a valuable layer to the understanding of virus-associated cancers and highlight the ongoing need for integrated approaches to infection management and cancer prevention.