Antiviral effect of Alloferon on Kaposi's sarcoma‐associated herpesvirus

Kaposi's sarcoma‐associated herpesvirus (KSHV) is a human gammaherpesvirus that is associated with the development of Kaposi's sarcoma and primary effusion lymphoma. KSHV establishes two alternate genetic life cycle programs upon infection of its host cells, which maintain a latent infection in infected cells but undergo lytic reactivation in response to various stimuli. In this study, we used BCBL‐1, persistent KSHV‐infected B lymphoma cell line, where the lytic and latent cycle of KSHV was regulated by TPA treatment. Alloferon is an immunomodulating peptide originating from insects which has been successfully developed in clinical trials as antiviral drug in Russia and showed remarkable effect on prevention of recurrent HSV infection. However, its specific mechanism remains to be clarified. We investigated the effect of alloferon on the regulation of lytic reactivation in viral infected cells. We found that alloferon effectively suppressed the down‐regulation of cell proliferation induced by TPA treatment. It suggests that the lytic reactivation of KSHV within BCBL‐1 can be regulated by alloferon. We next investigated the specific intracellular target of alloferon. Alloferon regulated the expression level of RTA as lytic switch protein, and that of ORF45 and vIRF2, which inhibit the production of type I IFNs. Therefore, we suggests that alloferon may be an effective antiviral agent on KSHV infection.