Monitoring processed, mature Human Immunodeficiency Virus type 1 particles immediately following treatment with a protease inhibitor-containing treatment regimen

Heather A Baird,Eric J Arts,Michael M Lederman,Andre J Marozsan,Donna Mildvan,Alan Landay,Daniel R Kuritzkes,Harold A Kessler

doi:10.1186/1742-6405-2-2

Abstract

Protease inhibitors (PIs) block HIV-1 maturation into an infectious virus particle by inhibiting the protease processing of gag and gag-pol precursor proteins. We have used a simple anti-HIV-1 p24 Western blot to monitor the processing of p55gag precursor into the mature p24 capsid immediately following the first dosage of a PI-containing treatment regimen. Evidence of PI activity was observed in plasma virus as early as 72 hours post treatment-initiation and was predictive of plasma viral RNA decrease at 4 weeks.

Highlights

And transport of the 55 kDa gag (p55gag) and 160 gag-pol (p160gag-pol) proteins to the inner plasma membrane is essential for the packaging of the viral genomic RNA, host tRNALys,3 primer, as well as for interactions with HIV-1 envelope glycoproteins [5]
FWigeustreern1blots for the HIV-1 gag proteins in HIV-1 produced in tissue culture following treatment with protease inhibitors Western blots for the HIV-1 gag proteins in HIV-1 produced in tissue culture following treatment with protease inhibitors
In summary HIV protease inhibitors block the processing of p55gag and p160gag-pol precursor proteins during virus budding or following virus release

Summary

Introduction

And transport of the 55 kDa gag (p55gag) and 160 gag-pol (p160gag-pol) proteins to the inner plasma membrane is essential for the packaging of the viral genomic RNA, host tRNALys, primer, as well as for interactions with HIV-1 envelope glycoproteins [5]. Budding and virus release initiates the processing of the gag and gag-pol precursor proteins. This processing step likely requires the dimerization of two gag-pol precursors (at least in the region of protease) that permits a low-efficiency cleavage of the precursor proteins and release of fully active protease (PR) homodimers [16]. These enzymes complete protein maturation to produce an infectious virus particle. In contrast other antiretroviral drugs (ARV) such as nucleoside reverse transcriptase inhibitors (NRTI) and non-nucleoside RT inhibitors (NNRTI), block reverse transcription during intracellular HIV-1 replication [3]

Methods

Results

Conclusion