tRNA retrograde transport and HIV-1 nuclear trafficking: a surprising connection. (360G-Wellcome-083810_Z_07_Z)

We have recently discovered that cytoplasmic tRNAs can be transported back into the nucleus in human cells, a process called retrograde tRNA transport, and that this process is exploited by HIV-1 to infect non dividing cells. We hypothesize that specific cellular factors drive nuclear import of tRNAs in human cells and that HIV-1 nuclear import is also promoted by the same factors. We aim to investigate this by: 1) Isolating the cellular factors driving tRNA nuclear import by chromatographic an d genetic approaches. 2) Disrupting their function by stable knock down or generation of dominant-negative mutants and examine the impact on HIV-1 infection in dividing and non-dividing cells. 3) Mapping the viral determinants for incorporation of and interaction with tRNAs with nuclear import activity by the generation of HIV-1 and murine leukaemia virus (MLV) mutants.