What is it about?
Our immune system must strike a delicate balance between fighting viruses and protecting the cells it needs to function. This study explores how two closely related proteins, Akt1 and Akt2, influence this balance during herpes simplex virus 1 (HSV-1) infection. Although often thought to have overlapping roles, we discovered that these proteins have distinct and non-redundant functions in infected cells. Akt2 helps infected cells survive by blocking signals that trigger their self-destruction and promotes immune signaling. In contrast, when Akt1 is missing, immune responses are delayed and weaker. These findings uncover a new layer of regulation in the immune system and help explain how the body controls infection while minimizing damage to its own tissues. This knowledge could eventually inform new strategies for managing herpes and other viral diseases.
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Photo by National Institute of Allergy and Infectious Diseases on Unsplash
Why is it important?
This work is important because it challenges the long-standing assumption that Akt1 and Akt2, which are closely related proteins involved in cell survival and immune signaling, perform redundant functions. We provide a new concept on how the immune system decides whether to fight infection aggressively or preserve infected cells. Our findings extend beyond herpes to broader viral and inflammatory diseases, where balancing cell survival and immune activation is critical.
Perspectives
This project was conceived and largely carried out at the onset of the COVID-19 pandemic, a time when the world was grappling with immense uncertainty and loss. We were driven by the intuition that immune system dysregulation was central to the severity of viral diseases, and we were eager to explore this concept through the lens of herpes simplex virus (HSV-1) infection. Our curiosity intensified when our knockout animal models began showing strikingly different responses to infection, hinting at an unrecognized layer of immune regulation. What makes this work even more meaningful is the remarkable dedication of the co-first authors, Rahul and Chandrashekhar, who continued their experiments under extraordinary circumstances. While the rest of the world was sheltering in place, they demonstrated the true spirit of scientific pursuit, placing discovery above personal comfort or safety, driven not by obligation, but by curiosity, courage, and a deep commitment to understanding viral immunology. Their effort embodies what it means to be a scientist in service of knowledge and humanity.
Deepak Shukla
University of Illinois at Chicago
Read the Original
This page is a summary of: Akt isoform specificity drives intrinsic immune regulation during HSV-1 infection, Proceedings of the National Academy of Sciences, July 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2504962122.
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