FIG. 10.

Model diagram summarizing the interaction of KSHV with receptors, the different stages involved in KSHV infection, and the various signal pathways induced by KSHV. The process of infection is divided into several distinct phases. (A) Binding and interaction with receptors. The initial attachment of the virus with the binding receptor HS molecules via its envelope glycoproteins gpK8.1A and gB is followed by temporally coordinated interactions with integrins (α3ß1, αVß3, and αVß5) and CD98-xCT molecules, leading to the formation of a multimolecular complex. (B) Induction of signal pathways and entry. Interactions with cell surface receptors trigger the cascades of host cell preexisting signal pathways. Integrin activation of FAK and Src leads to the activation of PI3-K and Rho-GTPases. These signal cascades lead to the formation of endocytic vesicles, and the internalization of KSHV occurs by endocytosis. (C) Transport of the virus. The endosome moves in the cytoplasm, and the release of the viral nucleocapsid into the cytoplasm occurs. RhoA facilitates the transport of capsid toward the nucleus by inducing microtubule stabilization and regulating microtubule dynamics via Dia-2. (D) Nuclear delivery. The viral DNA is delivered to the nucleus. (E) Gene expression. The initiation of viral-gene expression occurs with the help of KSHV binding- and entry-induced cellular signaling molecules and transcription factors, such as NF-κB and ERK1/2. The stage at which anti-CD98/xCT antibodies could be exerting their effect on blocking of viral-gene expression during KSHV infection is shown on the right.