Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem cell-derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue-specific EVs or cell type-specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in the signaling for physiological function and the maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines the current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Extracellular vesicles (EVs), a diverse group of cell-derived exocytosed particles, are pivotal in mediating intercellular communication due to their ability to selectively transfer biomolecules to specific cell types. EVs, composed of proteins, nucleic acids, and lipids, are taken up by cells to affect a variety of signaling cascades. Research in the field has primarily focused on stem-cell derived EVs, with a particular focus on mesenchymal stem cells, for their potential therapeutic benefits. Recently, tissue specific EVs or cell type specific extracellular vesicles (CTS-EVs), have garnered attention for their unique biogenesis and molecular composition because they enable highly targeted cell-specific communication. Various studies have outlined the roles that CTS-EVs play in signaling for physiological function and maintenance of homeostasis, including immune modulation, tissue regeneration, and organ development. These properties are also exploited for disease propagation, such as in cancer, neurological disorders, infectious diseases, autoimmune conditions, and more. The insights gained from analyzing CTS-EVs in different biological roles not only enhance our understanding of intercellular signaling and disease pathogenesis, but also open new avenues for innovative diagnostic biomarkers and therapeutic targets for a wide spectrum of medical conditions. This review comprehensively outlines current understanding of CTS-EV origins, function within normal physiology, and implications in diseased states.

Human herpesviruses (HHVs) are notorious, ubiquitous intracellular pathogens that establish lifelong infections in the host. They tightly manipulate host signaling pathways that play central roles in key cellular processes such as cell survival, metabolism, immune responses, and oncogenic transformation. Among the many pathways explored, the phosphatidylinositol-3-kinase (PI3K)/Akt signaling axis has emerged as a central and conserved target exploited by all eight HHVs. Herpesviruses can induce PI3K/Akt signaling at multiple stages of their life cycle, beginning at viral entry and extending through lytic replication, latency maintenance, immune evasion, and virus-associated tumorigenesis. Mechanistically, herpesviruses engage both host cell receptors and viral effector proteins to activate PI3K, drive Akt phosphorylation, and thereby orchestrate downstream signaling pathways that favor viral replication, survival, and immune evasion. Transient activation of this pathway supports viral replication, whereas sustained signaling promotes latent infection and oncogenesis, particularly in Epstein–Barr virus and Kaposi’s sarcoma-associated herpesvirus. This review provides a comparative analysis of PI3K/Akt pathway manipulation across all HHVs, highlighting shared strategies and virus-specific adaptations. We further discuss ongoing clinical trials and therapeutic opportunities targeting the PI3K/Akt axis, emphasizing its potential as a host-directed antiviral and anticancer strategy.