부산대학교 도서관

Herpesvirus infections are highly prevalent in the human population and persist for lifetime. They are often acquired subclinically but potentially progress to life31 threatening diseases in immunocompromised individuals. The interferon system is indispensable for the control of herpesviral replication. However, the responsible antiviral effector mechanisms are not well characterized. The type I interferon34 induced, human myxovirus resistance 2 (MX2) gene product MxB, a dynamin-like large GTPase, has recently been identified as potent inhibitor of HIV-1. We now show that MxB also interferes with an early step of herpesvirus replication, affecting α-, β-, and γ- herpesviruses before or at immediate early gene expression. Defined MxB mutants influencing GTP binding and hydrolysis reveal that the effector mechanism against herpesviruses is thoroughly different from that against HIV-1. Overall, our findings demonstrate that MxB serves as a broadly41 acting intracellular restriction factor that not only controls the establishment of retrovirus but also herpesvirus infection of all three subfamilies. Importance Human herpesviruses pose a constant threat to human health. Reactivation of persisting herpesvirus infections particularly in immunocompromised individuals and the elderly can cause severe diseases, such as zoster, pneumonia, encephalitis or cancer. The interferon system is relevant for the control of herpesvirus replication as exemplified by fatal disease outcomes in patients with primary immunodeficiencies. Here, we describe the interferon-induced, human MX2 gene product, MxB, as an efficient restriction factor of α-, β-, and γ- herpesviruses. MxB has previously been described as an inhibitor of HIV-1. Importantly, our mutational analyses of MxB reveal an antiviral mechanism of herpesvirus restriction distinct from that against HIV-1. Thus, the dynamin-like MxB GTPase serves as a broadly-acting intracellular restriction factor that controls retrovirus as well as herpesvirus infections. [ABSTRACT FROM AUTHOR]