Viral-host interactions mediated by the mTOR signaling pathway

The mechanistic target of rapamycin (mTOR) is an evolutionarily conserved serine/threonine kinase that regulates multiple key cellular processes. It assembles into two major multi-protein complexes, called mTOR complex (mTORC)1 and mTORC2, to integrate cues from cellular nutrient status, energy levels, and growth factors. The mTOR plays crucial roles in key physiological processes such as protein synthesis, autophagy initiation, lipid metabolism, and cell survival. As obligate intracellular parasites, viruses rely heavily on the host’s biosynthetic machinery, making viral propagation dependent on host-derived metabolic resources. Consequently, the metabolic networks and cellular functions governed by the mTOR pathway directly support the viral life cycle, establishing it as a critical regulatory node in virus-host interactions. To fulfil their replication demands, viruses have evolved diverse strategies to manipulate the mTOR signaling: sustained activation of host anabolic metabolism, selectively inhibiting the mTOR-mediated autophagy to generate membranous structures, or dynamically tuning mTORC1 and mTORC2 activities to meet stage-specific replication needs. This review systematically elucidates the structural basis and regulatory landscape of the mTOR signaling pathway, highlighting the specific mechanisms used by various viruses to modulate the mTOR function. It also examines the central role of mTOR in antiviral immunity and provides preclinical and clinical evidence supporting mTOR-targeted antiviral strategies. Ultimately, this review aims to outline a comprehensive theoretical framework for understanding virus-host interactions through mTOR modulation and offers novel perspectives on the development of mTOR-based antiviral interventions.