In VivoProcessing of Pr160gag-polfrom Human Immunodeficiency Virus Type 1 (HIV) in Acutely Infected, Cultured Human T-Lymphocytes
| Autor: | Horst Dr Lindhofer, Klaus Von Der Helm, Hans Nitschko |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
T-Lymphocytes
medicine.medical_treatment Human immunodeficiency virus (HIV) Gene Products gag Biology medicine.disease_cause Cleavage (embryo) gag Gene Products Human Immunodeficiency Virus Cell Line Substrate Specificity Scissile bond HIV Protease In vivo Virology medicine Humans Protein Precursors Saquinavir Antiserum Enzyme Precursors Binding Sites Protease HIV Protease Inhibitors Isoquinolines Molecular biology pol Gene Products Human Immunodeficiency Virus Quinolines Protein Processing Post-Translational |
| Zdroj: | Virology. 214:624-627 |
| ISSN: | 0042-6822 |
| DOI: | 10.1006/viro.1995.0074 |
| Popis: | The processing of the HIV-1 Pr160gag-polprecursor polyprotein was analyzed in freshly HIV-1-infected MT-4 cultured cells. Single intermediates of the processing cascade were characterized by immunoblotting using distinct antisera. A potent inhibitor of the HIV protease (PR), Ro 31-8959, was employed to block cleavage by the mature PR, thus allowing insights into initial stages of thegag-pol(auto)-catalytical processing. While most knowngag-polcleavages were blocked in the presence of the inhibitor, the cleavage site between thegag-NC and thepol-p6* domains was still cleaved even in presence of high amounts (1 μM) of inhibitor, leading to the accumulation of a novel 114-kDa polyprotein comprising p6*-PR-RT-IN. In the absence of inhibitor no accumulation of p114 was observed. In inhibitor-treated, HIV-1-infected cells a p6*-PR intermediate was also detected, indicating subsequent cleavage of the PR/RT scissile bond. These results demonstrate initial cleavage(s) of thegag-polprecursor hydrolyzed by a proteolytic activity different from the mature PR and indicate that p114 (p6*-PR-RT-IN) and p6*-PR intermediates could play an essential role in the PR activation process. |
| Databáze: | OpenAIRE |
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