Lessons learned by study at the retrovirus-host interface
• Patented retroviral structural gene vectors
• Discovered translation control mechanism conferred by retroviruses
• Elucidated the cellular effector protein and cognate cis-acting responsive elements in the 5′ UTR
• Solved the secondary structure of the cognate viral RNA element and cellular paralog
• Defined the molecular basis is DHX9/RNA helicase tethered to cognate viral and cellular mRNAs
• Quantified DICER suppresses synthesis of HIV-1 virion proteins
• Defined HIV-1 antagonizes DICER activity and requires the arginine-rich RNA binding domain in Tat
• Revealed HIV-1 downregulates host protein synthesis due to activating eIF4E inhibitory binding protein
• Characterized Vpr is necessary and sufficient for downregulation of host translation
• Discovered the retention of nuclear cap-binding protein provides HIV-1 resistance to eIF4E inhibition
• Distinguished distinct components of HIV-1 RNPs for protein synthesis and virion biogenesis
• Revealed unique capacity for reinitiation of translation by the translation RNP of human retroviruses
• Defined specific nuclear interactions that distinguish a viral RNP for virion biogenesis
• By usurping the cell’s gene expression machineries, retroviruses produce a dozen gene products from a single RNA.
• Distinctions in the viral RNPs are expected to reveal selectivity to pulling its Achilles’ heel.