Physical and functional interactions between STAT3 and Kaposi's sarcoma‐associated herpesvirus‐encoded LANA

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Abstract
The Kaposi's sarcoma‐associated herpesvirus (KSHV)‐encoded latency‐associated nuclear antigen (LANA) is known to modulate viral and cellular gene expression. We show that LANA directly associates with an interleukin‐6 signal transducer, signal transducer and activator of transcription 3 (STAT3) and that LANA enhances the transcriptional activity of STAT3. Coimmunoprecipitation studies documented a physical interaction between LANA and STAT3 in transiently transfected 293T cells as well as the KSHV‐infected primary effusion lymphoma (PEL) cell line. Furthermore, small‐interfering RNA‐mediated reduction of LANA expression decreased the STAT3‐dependent transcription in KSHV‐positive PEL cells, whereas overexpression of LANA enhanced STAT3 activity in KSHV‐negative B lymphoma cells. These data demonstrate that LANA is a transcriptional co‐activator of STAT3, and may have implications for the pathogenesis of KSHV‐associated diseases.