Abstract
The Rad18 DNA repair protein plays a central role in the response to DNA damage and has been suggested to bind to the human immunodeficiency virus type 1 (HIV-1) integrase (IN) and restrict the early steps of HIV-1 infection. However, the inhibitory mechanism of Rad18 is not fully understood. Here, we describe a series of experiments that indicate that Rad18 can suppress the late step of HIV-1 replication by inhibiting selective viral post-transcription and the production of infectious HIV-1 virions. Notably, Rad18 interacted with HIV-1 IN, Tat, and Vif proteins and hijacked them in the nucleoli. Therefore, Rad18 seems to suppress multiple steps of HIV-1 infection, including viral post-transcription, production, and infectivity. IMPORTANCE: Rad18, which contributes to damage bypass and DNA post-replication repair, is known to bind to HIV-1 IN and suppress HIV-1 infection. In this study, we found for the first time that Rad18 suppresses the late stages of HIV-1 infection. In addition to IN, we identified Tat and Vif as Rad18-interacting proteins. Rad18 may suppress multiple steps of the HIV-1 life cycle, including the early steps of HIV-1 infection, reverse transcription and integration, and the late steps of HIV-1 infection, viral post- transcription, viral production, and viral infectivity. These findings highlight the protective role of DNA repair proteins against retroviral infection and L1 retrotransposition as guardians of the human genome.