Raf/MEK/ERK signalling triggers reactivation of Kaposi's sarcoma-associated herpesvirus latency

Abstract

Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, primary effusion lymphoma and multicentric Castleman's disease. KSHV infection of cells produces both latent and lytic cycles of infection. In vivo, the virus is found predominantly in the latent state. In vitro, a lytic infection can be induced in KSHV-infected cells by treating with phorbol ester (TPA). However, the exact signalling events that lead to the reactivation of KSHV lytic infection are still elusive. Here, a role is demonstrated for B-Raf/MEK/ERK signalling in TPA-induced reactivation of KSHV latent infection. Inhibiting MEK/ERK signalling by using MEK-specific inhibitors decreased expression of the TPA-induced KSHV lytic-cycle gene ORF8. Transfection of BCBL-1 cells with B-Raf small interfering RNA inhibited TPA-induced KSHV lytic infection significantly. Additionally, overexpression of MEK1 induced a lytic cycle of KSHV infection in BCBL-1 cells. The significance of these findings in understanding the biology of KSHV-associated pathogenesis is discussed.

Kaposi's Sarcoma-Associated Herpesvirus-Induced Angiogenin Plays Roles in Latency via the Phospholipase Cγ Pathway: Blocking Angiogenin Inhibits Latent Gene Expression and Induces the Lytic Cycle

“…6C). As shown previously by Cohen et al (7) and Ford et al (10), TPA treatment led to a 7.8-fold increase in phospho-ERK levels. These results demonstrated that irrespective of the upstream pathway mediating ERK phosphorylation, this activation is essential for lytic cycle induction by both TPA and neomycin.…”

Intracellular Tat of Human Immunodeficiency Virus Type 1 Activates Lytic Cycle Replication of Kaposi's Sarcoma-Associated Herpesvirus: Role of JAK/STAT Signaling

“…Besides JAK/STAT signaling, huIL-6 also involves activation of mitogen-activated protein kinase and phosphatidylinositol-3-kinase/AKT pathways. More recent studies have indicated that Raf/MEK/ERK signaling modulates TPA-induced reactivation of KSHV latency (20,25); therefore, our results did not eliminate the possibility that another pathway(s) by huIL-6 may also be involved in this process.…”

Stimulation of Ebola virus production from persistent infection through activation of the Ras/MAPK pathway

“…We next tested to see whether latent ZEBOV infection, like other latent infections, such as herpesvirus or human immunodeficiency virus (HIV) (30)(31)(32), could be induced to replicate to higher titers through physiological treatments. Typically, RAW ZEBOVpi cells produced low levels of viral expression, as determined by GFP expression (Fig.…”