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Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...

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Measurement of BK-polyomavirus Non-Coding Control Region Driven Transcriptional Activity Via Flow Cytometry
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Polyomavirus BK neutralizing activity in human immunoglobulin preparations.

Parmjeet S Randhawa1, Kristine Schonder, Ron Shapiro

  • 1Division of Transplantation Pathology, Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15213, USA. randhawapa@msx.upmc.edu

Transplantation
|June 24, 2010
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Summary

Human intravenous immunoglobulins (IVIG) neutralize BK polyomavirus (BKV) in vitro. This study demonstrates IVIG’s potential as a treatment for BKV infection, offering hope for kidney transplant patients.

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Area of Science:

  • Virology
  • Immunology
  • Nephrology

Background:

  • BK polyomavirus (BKV) infection is a significant threat to kidney allografts, potentially causing nephropathy.
  • Currently, no definitive drug treatments exist for BKV infection.
  • Human intravenous immunoglobulins (IVIG) are used empirically, but their efficacy remains unproven.

Purpose of the Study:

  • To investigate the polyomavirus neutralizing activity of commercially available human IVIG preparations.
  • To determine if IVIG can inhibit BKV infection in host cells.

Main Methods:

  • Five lots of IVIG from two suppliers were tested for neutralizing activity against BKV and mouse polyomavirus.
  • Host cells were infected with viruses, with or without prior IVIG treatment.
  • Viral DNA yield was quantified after 7 days to measure neutralization.

Main Results:

  • Clinically relevant concentrations of IVIG inhibited BKV DNA yield by over 90% in vitro.
  • The neutralizing effect was diminished when cells were pretreated with immunoglobulin or when treatment was delayed, suggesting a direct mechanism.

Conclusions:

  • Human IVIG preparations possess BKV-neutralizing antibodies.
  • The findings support further investigation into IVIG's role in treating BKV infection and provide data for clinical trial dose exploration.