Expression of mutant and wild-type gag proteins for gene therapy in HIV-1 infection

The effect of expression of defective HIV-based retroviral constructs in CD4-positive lymphocytes on subsequent infection of the cell by HIV-1 was studied. A vector containing a N terminally elongated gag protein which was noncleavable and myristoylation negative was not effective at inhibiting HIV assembly or viral replication in the culture. Expression of a wild-type HIV gag in trans led to an increase in cytopathicity within the culture such that all the cells died. A control LTR containing vector had no effect. A myristoylation negative gag would not appear to be a useful dominant negative inhibitor of HIV replication, but might be usable as a post-exposure immunogen. Post-infective immunisation with wild-type HIV-1 gag would appear to risk increasing virus-related cytopathicity.