Glutamine supplementation suppresses herpes simplex virus reactivation
Kening Wang, … , Philip R. Krause, Jeffrey I. Cohen
Kening Wang, … , Philip R. Krause, Jeffrey I. Cohen
Published June 5, 2017
Citation Information: J Clin Invest. 2017;127(7):2626-2630. https://doi.org/10.1172/JCI88990.
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Brief Report Virology

Glutamine supplementation suppresses herpes simplex virus reactivation

Abstract

Chronic viral infections are difficult to treat, and new approaches are needed, particularly those aimed at reducing reactivation by enhancing immune responses. Herpes simplex virus (HSV) establishes latency and reactivates frequently, and breakthrough reactivation can occur despite suppressive antiviral therapy. Virus-specific T cells are important to control HSV, and proliferation of activated T cells requires increased metabolism of glutamine. Here, we found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1–infected mice and HSV-2–infected guinea pigs. Transcriptome analysis of trigeminal ganglia from latently HSV-1–infected, glutamine-treated WT mice showed upregulation of several IFN-γ–inducible genes. In contrast to WT mice, supplemental glutamine was ineffective in reducing the rate of HSV-1 reactivation in latently HSV-1–infected IFN-γ–KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-γ–producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-γ–associated immune response and reduce the rate of reactivation of latent virus infection.

Authors

Kening Wang, Yo Hoshino, Kennichi Dowdell, Marta Bosch-Marce, Timothy G. Myers, Mayra Sarmiento, Lesley Pesnicak, Philip R. Krause, Jeffrey I. Cohen

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Figure 1

Reactivation of HSV-1 in trigeminal ganglia of mice receiving glutamine, glycine, or no supplement in their drinking water.

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Reactivation of HSV-1 in trigeminal ganglia of mice receiving glutamine,...
Animals were inoculated with HSV-1 by corneal scarification, received supplemental amino acid 2 weeks later, and then, after an additional 2 weeks, were anesthetized and their eyes exposed to UV irradiation. Two days later, animals were euthanized, trigeminal ganglia were removed and homogenized, homogenates were plated onto Vero cell monolayers, and the number of ganglia with reactivated virus was determined. Three separate experiments were performed (A–C), and results at day 5 in culture for all 3 experiments are shown (D). Experiment 1 had 25 mice in each group, and experiments 2 and 3 had 15 mice each in the glutamine and glycine groups and 7 and 10 mice in the no supplement group, respectively. Fisher’s exact test was used for statistics.