Model of dynamic SCV positioning during the course of host cell infection. (A) Following invasion, SCVs move centripetally toward the host cell nucleus in an SPI-2-independent manner. Rab7 GTPase recruits Rab7-interacting lysosomal protein (RILP) that brings the dynein/dynactin complex to the SCV (21, 24, 37), mediating SCV movement toward the host cell nucleus. The SPI-1 effector SopB is involved in mediating the juxtanuclear positioning of SCVs through activation of the nonmuscle myosin II actin motor via Rho GTPases (57) and persists for up to 12 h after invasion (14). The SPI-1 effector SipA also persists on the SCV for up to 8 hpi and cooperates with the SPI-2 T3SS effector SifA to mediate perinuclear SCV positioning (6). (B) By 8 to 14 hpi, SCVs have localized to their characteristic juxtanuclear position. SPI-2 effectors including the Golgi apparatus-tethering and/or dynein-recruiting effectors SseG (2, 42) and SseF (2) and the kinesin-inhibiting effector SifA (5) maintain the juxtanuclear positioning of SCVs (27, 41). Bacterial replication and SIF formation occur. Although the kinesin-linking SPI-2 effector PipB2 is also localized to SCVs, its effect on SCV positioning is masked by the combined actions of SipA, SopB, SifA, SseG, and SseF, which retain SCVs at juxtanuclear positions. PipB2 is involved in the extension of SIFs at this stage of infection (26, 34, 41). (C) At later times postinfection (≥14 h), SCVs move centrifugally toward the host cell periphery in a manner dependent upon the host microtubule network, active bacterial protein synthesis, an intact SPI-2 T3SS, the kinesin-recruiting effector PipB2, and host kinesin. Movement toward the host cell periphery may facilitate escape from the host cell and/or cell-to-cell transfer. (D) During the course of a 24-h infection, levels of SPI-2 effector proteins such as SifA and PipB2 increase (dotted line) while levels of SPI-1 effector proteins such as SipA and SopB decrease (solid line). These changes in effector protein levels are associated with centrifugal displacement of SCVs.