Positive and Negative Aspects of the Human Immunodeficiency Virus Protease: Development of Inhibitors versus Its Role in AIDS Pathogenesis

Author:

Ikuta Kazuyoshi12,Suzuki Satoko2,Horikoshi Haruko1,Mukai Tetsu1,Luftig Ronald B.3

Affiliation:

1. Department of Virology, Research Institute for Microbial Diseases (Biken), Osaka University, Suita, Osaka 565-0871,1 and

2. Section of Serology, Institute of Immunological Science, Hokkaido University, Kita-ku, Sapporo 060-0815,2 Japan, and

3. Department of Microbiology, Immunology and Parasitology, Louisiana State University Medical Center, New Orleans, Louisiana 70112-13933

Abstract

SUMMARY In this review we summarize multiple aspects of the human immunodeficiency virus (HIV) protease from both structural and functional viewpoints. After an introductory overview, we provide an up-to-date status report on protease inhibitors (PI). This proceeds from a discussion of PI structural design, to how PI are optimally utilized in highly active antiretroviral triple therapy (one PI along with two reverse transcriptase inhibitors), the emergence of PI resistance, and the natural role of secretory leukocyte PI. Then we switch to another focus: the interaction of HIV protease with other genes in acute and persistent infection, which in turn may have an effect on AIDS pathogenesis. We conclude with a discussion on future directions in HIV treatment, involving multiple-target anti-HIV therapy, vaccine development, and novel reactivation-inhibitory reagents.

Publisher

American Society for Microbiology

Subject

Molecular Biology,Microbiology,Infectious Diseases

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