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Inhibition of retroviral protease activity by an aspartyl proteinase inhibitor

Nature volume 329, pages 654–656 (1987)Cite this article

Abstract

Retrovirus protease is an enzyme that cleaves gag and gag-pol precursor polyproteins into the functional proteins of mature virus particles1,2. The correct processing of precursor polyproteins is necessary for the infectivity of virus particles: in vitro mutagenesis which introduces deletions into the murine leukaemia virus genome produces a protease-defective virus of immature core form and lacking infectivity3,4. A therapeutic drug effective against disease caused by retrovirus proliferation could likewise interfere with virus maturation. The primary structure has so far been determined for the protease of avian myeloblastosis virus5, and of murine6, feline7 and bovine8 leukaemia viruses. Amino acid sequencing of the retrovirus proteases, either after their purification or from prediction from the nucleotide sequence, shows that they possess the Asp-Thr-Gly sequence characteristic of the aspartyl pro-teinases. In this report we show that retrovirus proteases belong to the aspartyl proteinase group and demonstrate an inhibition by the aspartyl proteinase-specific inhibitor, pepstatin A, on the activity of bovine leukaemia, Moloney murine leukaemia and human T-cell leukaemia virus proteases.

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Authors and Affiliations

  1. Laboratory of Molecular Oncology, Tsukuba Life Science Center, Institute of Physical and Chemical Research, 3-1 Koyadai, Yatabe, Ibaraki, 305, Japan

    Iyoko Katoh & Yoji Ikawa

  2. Computer Center, Institute of Physical and Chemical Research, Wako, Saitama, 351-01, Japan

    Teruo Yasunaga

  3. Japan Immunoresearch Laboratories Ltd., 17-5 Sakae, Takasaki, Gunma, 370, Japan

    Yoshiyuki Yoshinaka

Authors
  1. Iyoko Katoh
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  2. Teruo Yasunaga
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  3. Yoji Ikawa
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  4. Yoshiyuki Yoshinaka
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Katoh, I., Yasunaga, T., Ikawa, Y. et al. Inhibition of retroviral protease activity by an aspartyl proteinase inhibitor. Nature 329, 654–656 (1987). https://doi.org/10.1038/329654a0

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