KSHV RTA Induces Degradation of the Host Transcription Repressor ID2 To Promote the Viral Lytic Cycle.

The immediate early viral protein replication and transcription activator (RTA) of Kaposi's sarcoma-associated herpesvirus (KSHV) is essential for activating the lytic cycle of KSHV. RTA induces the KSHV lytic cycle by several mechanisms, acting as a viral transcription factor that directly induces viral and host genes and acting as a viral E3 ubiquitin ligase by degrading host proteins that block viral lytic replication. Recently, we have characterized the global gene expression changes in primary effusion lymphoma (PEL) upon lytic reactivation of KSHV, which also led to the identification of rapidly downregulated genes such as ID2, an inhibitor of basic helix-loop-helix transcription factors.

KDM2B Overexpression Facilitates Lytic KSHV Infection by Inducing AP-1 Activity Through Interaction with the SCF E3 Ubiquitin Ligase Complex.

It is still largely unknown what host factors are involved in controlling the expression of the lytic viral gene RTA during primary infection, which determines if Kaposi's sarcoma-associated herpesvirus (KSHV) establishes latent or lytic infection. We have recently identified the histone demethylase KDM2B as a repressor of RTA expression during both KSHV infection and latency based on an epigenetic factor siRNA screen. Here, we report that surprisingly, KDM2B overexpression can promote lytic infection by using a mechanism that differs from what is needed for its repressor function.

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.

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.

Genome-Wide Identification of Direct RTA Targets Reveals Key Host Factors for Kaposi's Sarcoma-Associated Herpesvirus Lytic Reactivation.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus, which maintains the persistent infection of the host by intermittently reactivating from latently infected cells to produce viral progenies. While it is established that the replication and transcription activator (RTA) viral transcription factor is required for the induction of lytic viral genes for KSHV lytic reactivation, it is still unknown to what extent RTA alters the host transcriptome to promote KSHV lytic cycle and viral pathogenesis. To address this question, we performed a comprehensive time course transcriptome analysis during KSHV reactivation in B-cell lymphoma cells and determined RTA-binding sites on both the viral and host genomes, which resulted in the identification of the core RTA-induced host genes (core RIGs).

Guillain-Barre syndrome in a patient with diffuse large B-cell lymphoma, and rituximab maintenance therapy. An association beyond anecdotal evidence?

Paraneoplastic neurological syndromes constitute an unusual manifestation of cancer. The objective of this case report is to debate the association between rituximab therapy and Guillain-Barre syndrome. We present the case of a 57 years old patient, with diffuse large-B cell lymphoma in complete remission, who consulted our hospital because of symmetric lower extremity weakness, developed while being treated with a rituximab maintenance schedule.