A model to explain one potential role for productive infections by KSHV in KS lesions. (I) KSHV (shown as an enveloped iscosahedral core) can infect cuboidal endothelial cells and (II) induce a spindle-shaped morphology in these cells. These infected spindle-shaped cells can proliferate, lose KSHV rapidly, and (III) revert to uninfected, cuboidal cells. (IV) The spindle-shaped cells also can support production of KSHV. (V) The released KSHV can infect more cells, inducing the change to the spindle shape and maintenance of the infected lesion.