Comparative analysis of the viral interferon regulatory factors of KSHV for their requisite for virus production and inhibition of the type I interferon pathway.

Unique among human viruses, Kaposi's sarcoma-associated herpesvirus (KSHV) encodes several homologs of cellular interferon regulatory factors (vIRFs). Since KSHV expresses multiple factors that can inhibit interferon (IFN) signaling to promote virus production, it is still unclear to what extent vIRFs contribute to these specific processes during KSHV infection. To study the function of vIRFs during viral infection, we engineered 3xFLAG-tagged-vIRF and vIRF-knockout recombinant KSHV clones, which were utilized to test vIRF expression, as well as their requirement for viral replication, virus production, and inhibition of the type I IFN pathway in different models of lytic KSHV infection.

Epigenetic factor siRNA screen during primary KSHV infection identifies novel host restriction factors for the lytic cycle of KSHV.

Establishment of viral latency is not only essential for lifelong Kaposi's sarcoma-associated herpesvirus (KSHV) infection, but it is also a prerequisite of viral tumorigenesis. The latent viral DNA has a complex chromatin structure, which is established in a stepwise manner regulated by host epigenetic factors during de novo infection. However, despite the importance of viral latency in KSHV pathogenesis, we still have limited information about the repertoire of epigenetic factors that are critical for the establishment and maintenance of KSHV latency.

Characterization of de novo lytic infection of dermal lymphatic microvascular endothelial cells by Kaposi's sarcoma-associated herpesvirus.

The biology of primary lytic Kaposi's sarcoma-associated herpesvirus (KSHV) infection is still not well understood, which is largely attributed to the lack of cell lines permissive to robust lytic KSHV infection in vitro. Our study demonstrates that primary human dermal lymphatic microvascular endothelial cells (HDLMEC) support lytic KSHV replication following de novo infection, resulting in robust KSHV production, indicating that HDLMECs are suitable for studying the regulation of primary lytic KSHV infection. Importantly, by utilizing lytically infected HDLMECs, we show for the first time that the KSHV latent genes LANA and viral cyclin are required for lytic replication during de novo lytic infection, a function of these latent genes that has not yet been recognized.