AIDS Research

C. Burrell, P. Li, H. Peng, J. Carr, H. Ramshaw, A. Stephenson, H. Hocking, D. Callison, J. Calvert, T.W. Kok, A. Davis, B. Bela, N. Vandegraaff, A. Purins

The main focus of the laboratory is to study the molecular mechanisms and controls in the early phase of the HIV replication cycle, primarily from the initiation of viral infection up to integration of proviral DNA into the host genome. To facilitate such studies, cellular model systems have been characterised to produce a one-step virus growth cycle following initiation of infection by either cell-free virus infection or cell-to-cell transmission of viral infection. A concurrent aim is to identify features unique to one or the other mode of infection. A second theme that has evolved from the main theme of research is the study of intervention of the early events in HIV replication by gene-transfer techniques. A revised model for retroviral reverse transcription based on displacement synthesis of the plus strand strong-stop DNA, was used to design novel anti-HIV retroviral vectors targeted at viral reverse transcription (anti-RTn). These vectors have demonstrated marked long-term inhibition of HIV replication.

In 1996 major progress was made in several areas. Model systems aimed to classify the roles of HIV-infected macrophages in cell-to-cell viral transmission and in the induction of T cell apoptosis have been established. Murine leukaemia virus (MLV) mutants carrying nuclear localization sequences (NLS) have been selected. These mutants will be used to investigate the exact role of NLS in facilitating nuclear transportation of retroviral preintegration complexes in non-dividing cells and to assess the potential of MLV-NLS as retroviral vectors.