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.
Miele
G
G
University of Cambridge Department of Medicine, Addenbrooke's Hospital, UK.
Lever
A M
AM
D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000235:genetics; D015870:Gene Expression; D015683:Gene Products, gag / Q000235:genetics* / Q000378:metabolism; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D015658:HIV Infections / Q000235:genetics / Q000628:therapy* / Q000821:virology; D015497:HIV-1 / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D006801:Humans; D009154:Mutation; D009226:Myristates / Q000378:metabolism; D014779:Virus Replication / Q000235:genetics
D015683:Gene Products, gag; D009226:Myristates