Kaposi's sarcoma-associated herpesvirus inhibits interleukin-4-mediated STAT6 phosphorylation to regulate apoptosis and maintain latency

摘要: Cytokine-mediated JAK/STAT signaling controls numerous important biologic responses like immune function, cellular growth, and differentiation. Inappropriate activation of this pathway is associated with a range malignancies. Kaposi's sarcoma-associated herpesvirus (KSHV) the infectious viral agent sarcoma may also contribute to B-cell disorders, which include primary effusion lymphoma (PEL) multicentric Castleman's disease. However, regulation cytokine-mediated lymphocytic response by KSHV not fully understood. In report, we demonstrate that suppresses interleukin-4 (IL-4)-stimulated B-lymphocyte cell proliferation. Moreover, show latency-associated nuclear antigen (LANA) encoded essential for blocking IL-4-induced signaling. LANA reduces phosphorylation signal transducers activators transcription 6 (STAT6) on Y-641 concomitantly its DNA binding ability. Importantly, knockdown endogenous STAT6 dramatically increases sensitivity PEL cells low-serum stress or chemical-mediated apoptosis reactivation from latent replication. Thus, these findings suggest IL-4/STAT6 network precisely controlled survival, maintenance latency, suppression host cytokine virus-infected cells.