Molecular Mechanisms of Cytopathogenicity of Primate Lymphotropic Retroviruses:Relevance to Treatment and Vaccine for Aids

摘要

Studies were designed to examine the molecular mechanism of cytopathogenesis ofPrimate Lymphotropic Viruses, with the particular emphasis on examining the factors relevant to the design of treatment and vaccine programs to combat infections with (Human Immunodeficiency Virus). Three parallel approaches were followed in the course of this work. The results for the third year are as follows: To obtain a better understanding of viral gene function involved in cell killing, a series of deletion mutants of the viral genome was generated and the biological consequences of these mutations were examined by transfection into recipient host cells. Our results have shown that mutations in the carboxy region of gp41 show of gp41 show dramatic changes in the cell-to-cell transmission and cytopathic properties of the virus. Mutations in the 5' region result in packaging defective genomes which lead to the formation of morphologically normal viral particles but which are devoid of viral RNA, and therefore exhibit greatly diminished infectivity; and the molecular mechanism of transactivation by Tat was examined to elucidate the events that trigger the transition from a low level latent infection to productive HIV-1 replication. The Tat activity studies demonstrated direct binding of Tat to TAR RNA, a synergistic stimulation of LTR by Tat and mitogens, and both transcriptional and postranscriptional activation mechanisms by Tat. Keywords: HIV-1, Lymphotropic viruses, Cytopathogenicity, DNA sequences, Gene function, Transactivation, RA 1, AIDS, Tat, RNA. (JG)