Figure 4.

Ku70 is an indispensable host cellular factor in the early and late stages of the HIV-1 replication cycle. The interaction of IN with Ku70 during HIV reverse transcription prevents IN from degradation by the K48-linked Ub proteasome pathway. The interaction between Ku70 and IN decreases the modification level of IN by Ub in the cells. During the integration step, the initial binding of Ku70 and HIV-1 IN facilitates the recruitment of other members of the DNA-PK complex to the post-integration site. Then Ku70 serves as a member of DNA-PK and participates in the DNA gaps repair process through the NHEJ pathway, thereby completing the integration of viral DNA into the cell genome and enabling the HIV-1 viral replication. Ku70 is also packaged into HIV particles as early as its assembly stage and becomes part of HIV virions, and this process is mediated by HIV IN.