| Retroviral replication is dependent on a unique replicative strategy that relies on a myriad of viral-host cell protein interactions. Retroviral proteins have evolved to recruit host cell proteins to facilitate the integration of viral DNA into the host genome. Here we describe experiments that implicate roles for three cellular proteins, Translin-Associated Factor X (TSNAX), the nucleoporin-associated protein ALADIN and the kinesin superfamily member 4 (KIF4), in the early phase of the retroviral life cycle. First, we discuss experiments that suggest that TSNAX is required for retroviral transduction efficiency. TSNAX was identified as a Fasciculation and elongation protein zeta-1 (FEZ1)-interacting protein by yeast two-hybrid and we were able to verify this interaction in vivo. We found that RNA interference (RNAi) of TSNAX reduces transduction efficiency of both complex and simple retroviruses in a cell-type and species-independent manner. However, expression of RNAi-resistant TSNAX did not restore transduction efficiency in TSNAX-depleted. The finding that silencing of Disrupted-In-Schizophrenia 1 (DISC1), another FEZ1-interacting protein, also reduces retroviral infection led us to explore a role for TSNAX/DISC1 fusion proteins in retroviral infection. Interestingly, FEZ1, TSNAX and DISC1 have all been implicated in microtubule dynamics. Thus, these findings may provide insight into microtubule-based retroviral transport. Secondly, we discuss evidence for a role for KIF4 during retroviral replication. We propose that KIF4 may mediate the anterograde transport necessary for retroviruses to transition from the microtubule organizing center (MTOC) to the nucleus. Finally, we discuss a study into the role of ALADIN in the retroviral life cycle. Prior to this investigation, ALADIN was identified as a Murine Leukemia Virus (MuLV) p12-interacting protein. p12 has been implicated in mediating the nuclear localization of the MuLV pre-integration complex (PIC). We found that retroviral infection is reduced in cell lines derived from patients with triple-A syndrome, a disease associated with mutations in the gene encoding ALADIN. We also demonstrate that depletion of ALADIN in a cultured cell line results in a modest reduction of MuLV infection. Together, these findings may provide insight into microtubule-dependent retroviral transport and the transition of retroviruses from the MTOC to the nucleus. |
