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A Primary Neuron Culture System for the Study of Herpes Simplex Virus Latency and Reactivation
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Published on: April 2, 2012

Inhibition of herpes simplex virus multiplication by activated macrophages: a role for arginase?

P Wildy, P G Gell, J Rhodes

    Infection and Immunity
    |July 1, 1982
    PubMed

    Insights

    Activated macrophages prevent herpes simplex virus infection in nearby cells by releasing arginase, an enzyme that depletes arginine. This effect, observed in vitro, can be reversed by adding extra arginine.

    Area of Science:

    • Immunology
    • Virology

    Background:

    • Macrophages play a crucial role in innate immunity against viral infections.
    • Herpes simplex virus (HSV) and vaccinia virus are significant human pathogens.
    • Arginine availability is essential for efficient viral replication.

    Purpose of the Study:

    • To investigate the mechanism by which activated macrophages inhibit productive viral infection in neighboring cells.
    • To determine the role of arginase in this macrophage-mediated antiviral effect.

    Main Methods:

    • In vitro co-culture experiments using proteose-peptone-activated mouse macrophages and virus-infected cells.
    • Assessment of viral replication in the presence and absence of macrophages.
    • Manipulation of arginine levels in the culture medium.
    • Measurement of arginase activity (intracellular and extracellular).

    Main Results:

    • Activated macrophages prevented productive infection by herpes simplex virus and vaccinia virus in neighboring cells, irrespective of species.
    • The antiviral effect was mediated by extracellular arginase released from macrophages.
    • The effect was dependent on arginine availability and could be reversed by arginine supplementation.
    • Extracellular arginase demonstrated significant stability under tissue culture conditions.

    Conclusions:

    • Activated macrophages employ a soluble factor, arginase, to limit productive viral infections in adjacent cells.
    • Arginase-induced arginine depletion is a key mechanism for macrophage-mediated antiviral defense.
    • This mechanism is effective against both herpes simplex virus and vaccinia virus.

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