Akt isoform specificity drives intrinsic immune regulation during HSV-1 infection

• 成果类型: Article
• 署名作者: Suryawanshi, Rahul K.; Patil, Chandrashekhar D.; Borase, Hemant; Shukla, Deepak
• 署名单位: University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID); University of Illinois System; University of Illinois Chicago; University of Illinois Chicago Hospital
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-9416
• DOI: 10.1073/pnas.2504962122
• 发表日期: 2025-07-08
• 关键词: apoptosis; mice

摘要

Akt isoforms are generally considered functionally redundant, contributing to total Akt activity. However, during HSV-1 infection, Akt1 and Akt2 knockout animals exhibited distinct antiviral responses. Unexpectedly, in the absence of Akt1, Akt2 played a unique role in regulating cytokine production and inactivating proapoptotic transcription factor FoxO3a, a mechanism not shared by Akt1. These findings provide the clearest in vivo evidence yet that Akt isoforms are not functionally redundant, revealing distinct immune-regulatory roles for each isoform and suggesting a broader principle for fine-tuning immunity and cell death across diverse pathological settings.