This is a proposal to explore the multiple nuclear localization signals present on viral proteins found in the preintegration complex. Experiments, based on experiments from the preliminary results section, are proposed to characterize the NLSs in integrase and Vpr. In addition, many experiments will be performed to comprehensively address the possibility that multiple NLSs work in concert to mediate nuclear entry, to determine the effect of mutations in identified NLSs on replication, to compare HIV with MLV, and to identify the pathway used by the virus for nuclear entry.
| Bouyac-Bertoia, M; Dvorin, J D; Fouchier, R A et al. (2001) HIV-1 infection requires a functional integrase NLS. Mol Cell 7:1025-35 |
| O'Doherty, U; Swiggard, W J; Malim, M H (2000) Human immunodeficiency virus type 1 spinoculation enhances infection through virus binding. J Virol 74:10074-80 |
| Palmeri, D; Malim, M H (1999) Importin beta can mediate the nuclear import of an arginine-rich nuclear localization signal in the absence of importin alpha. Mol Cell Biol 19:1218-25 |
| Fouchier, R A; Meyer, B E; Simon, J H et al. (1998) Interaction of the human immunodeficiency virus type 1 Vpr protein with the nuclear pore complex. J Virol 72:6004-13 |
