
doi: 10.1042/bst0200513
pmid: 1397651
513 IIIV proteinase is a member of the aspartic I Iurnan immunodeficiency virus (1 IlV), the causative agent of acquired immunodeficiency syndrome (AII)S)9 is a retrovirus. In common with other retroviruses and many other KNA viruses, some of its gene products are expressed in host cells as polyproteins which require subsequent processing by proteinases to give smaller, functional proteins. For I IIV three genes are expressed as polyproteins; these are gug pol and en71 1 1 1, ‘I’he en71 gene codes for ii 160 kI)a protein which is subsequently cleaved to yield the two envelope proteins of the virus, gp 120 and gp-l 1 . This processing appears t o be carried out by a host cell proteinase. ‘I’he gag gene encodes the structural proteins of the core of the virus and the pol gene the enzymes of the virus; a proteinase, reverse transcriptase, KNAse € I and integrase. ‘I’he pol gene is translated only as a gag-pol fusion protein resulting from a frame shift betueen the overlapping gug and pol reading frames. The ratio o f translation of guglgag-pol is approximately 20: 1. The gag and gag-pol gene products are totally processed by the proteinase encoded within the pol gene 121, a process which involves the autocatalytic release of this proteinase from its precursor polyprotein. Electron microscopic observation 1.3 1 of the budding and maturation of I IIV suggests that the processing of gug and gag-pol polyproteins occurs during. or soon after, the budding of the new virus particles from the host cell membrane. This results in a morphological change in the virus. reflecting its maturation from a non-infectious to an infectious fomi. If a mutation is introduced into the proviral I)NA which renders the viral proteinase inactive, then the resultant virions are not infectious 141. A similar study with Moloney murine leukaemia virus demonstrated that the loss of infectivity resulting from a mutation in its proteinase was reflected in the virus particles remaining in their immature ‘doughnut’ form 151. An inhibitor of the proteinase should be able to give the same effect and hence have anti-viral activity by preventing the spread of infection.
Genes, Viral, HIV Protease Inhibitors, Isoquinolines, Virus Replication, Antiviral Agents, Cell Line, Kinetics, HIV-2, HIV-1, Quinolines, Humans, Saquinavir
Genes, Viral, HIV Protease Inhibitors, Isoquinolines, Virus Replication, Antiviral Agents, Cell Line, Kinetics, HIV-2, HIV-1, Quinolines, Humans, Saquinavir
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