Model depicting the impact of CIB1 shRNA on KSHV macropinocytosis and productive <i>de novo</i> infection in HMVEC-d cells.

<p>CIB1-shRNA transduction in HMVEC-d cells resulted in the following consequences which are depicted by the red lines: (i) CIB1 protein level was reduced by >90%; (ii) CIB1 association with EphA2 and the associated KSHV induced Src-PI3-K-c-Cbl signal complex was significantly reduced; (iii) KSHV induced EphA2 activation was not sustained and as a consequence, downstream Src and Erk1/2 signal amplification was significantly abrogated; (iv) EphA2 association with Src-PI3-k-c-Cbl signal complex was substantially reduced; (v) EphA2 association with actin modulating myosin IIA and alpha actinin-4 were almost abolished, (vi) as a consequence, actin cytoskeletal rearrangement and membrane blebbing was inhibited, which (vii) impaired KSHV macropinocytosis, productive trafficking, and establishment of <i>de novo</i> infection.