The ins and outs of virus trafficking through acidic Ca²⁺ stores

Many viruses exploit host-cell Ca²⁺ signaling processes throughout their life cycle. This is especially relevant for viruses that translocate through the endolysosomal system, where cellular infection is keyed to the microenvironment of these acidic Ca²⁺ stores and Ca²⁺-dependent trafficking pathways. As regulators of the endolysosomal ionic milieu and trafficking dynamics, two families of endolysosomal Ca²⁺-permeable cation channels - two pore channels (TPCs) and transient receptor potential mucolipins (TRPMLs) - have emerged as important host-cell factors in viral entry. Here, we review: (i) current evidence implicating Ca²⁺ signaling in viral translocation through the endolysosomal system, (ii) the roles of these ion channels in supporting cellular infection by different viruses, and (iii) areas for future research that will help define the potential of TPC and TRPML ligands as progressible antiviral agents.