Positive-Sense RNA Viruses Reprogramming Membrane Contact Sites to Remodel Organelles and Control Cell Fate

Eukaryotic cells rely on a highly coordinated organelle network to maintain metabolism, signaling, stress adaptation and cell survival. Membrane contact sites (MCSs) provide essential platforms for inter-organelle communication. As obligate intracellular parasites, less attention has been given to how viral perturbation of MCSs may reshape the broader organelle communication network. In this review, we focus on positive-sense RNA viruses and virus-induced membrane contact sites (vMCSs), focusing on ER-associated tethering factors, lipid transfer pathways, calcium signaling modules, and replication organelle–host organelle interfaces. Also we discuss how viruses hijack conserved host tethering systems to connect viral replication compartments with lipid transfer machinery. Further, we explore how viruses establish vMCSs that couple replication compartments to host organelles, thereby coordinating cellular homeostasis. Together, these findings suggest that viral remodeling of MCSs should be understood not only as local manipulation of individual organelles but also as a network-level reorganization of cellular homeostasis.