Specific Interaction between eEF1A and HIV RT Is Critical for HIV-1 Reverse Transcription and a Potential Anti-HIV Target
Fig 8
Did B inhibits early HIV-1 replication by targeting the RT-eEF1A interaction.
Immediately following fusion of the viral and cellular membrane, the viral core and matrix are released into the cytoplasm. Subsequently the viral core undergoes uncoating and reverse transcription. Here we propose that eEF1A is recruited to the RTC by a direct interaction with RT that increases the efficiency of reverse transcription completion. It is unclear if virion eEF1A [12], target cell eEF1A or both are required. HIV-1 containing a W252A RT mutant has decreased ability to interact with eEF1A. Treating cells with Did B generates pools of eEF1A-Did B as well was RT-eEF1A-DidB complexes. The RT-eEF1A-Did B complex does not support uncoating and reverse transcription and results in decreased RTC levels and reduced DNA synthesis. The status of other RTC protein interactions requires experimental confirmation (as denoted by a “?”). However, a W252A RT mutant HIV-1 is unaffected by Did B because its interaction with eEF1A, or with a eEF1A - Did B complex, is downregulated and catalyzes reverse transcription in either the presence or absence of Did B albeit at reduced efficiency.