A role for the aspartyl protease from the human immunodeficiency virus type 1 (HIV-1) in the orchestration of virus assembly.
Functional HIV-1 protease (PR) is required for the maturation of viral proteins, for the appearance of characteristic structural features in the virion (as determined by electron microscopy), and for the final assembly of mature virus. Most importantly, HIV-1 PR activity is required for the development of infectivity. Still largely undefined, however, is the timing and control of protease action in this assembly process. Based on the three-dimensional structure of HIV-1 PR2,3 and experimental data reported in the literature, we propose a comprehensive virus assembly model that highlights the role of HIV-1 PR, suggests further experiments to verify the validity of the model, and poses specific questions relevant to the ultimate exploitation of HIV-1 protease as a therapeutic target.
Navia
M A
MA
Merck Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065.
McKeever
B M
BM
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry / Q000378:metabolism*; D016333:HIV Protease / Q000737:chemistry / Q000378:metabolism*; D015497:HIV-1 / Q000201:enzymology* / Q000254:growth & development; D006801:Humans; D008954:Models, Biological; D014779:Virus Replication; D014961:X-Ray Diffraction
D016282:Aspartic Acid Endopeptidases; D016333:HIV Protease