Glutamine supplementation suppresses herpes simplex virus reactivation
Kening Wang, Yo Hoshino, Kennichi Dowdell, Marta Bosch-Marce, Timothy G. Myers, Mayra Sarmiento, Lesley Pesnicak, Philip R. Krause, Jeffrey I. Cohen
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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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 3

Reactivation of HSV-1 from trigeminal ganglia of WT and IFN-γ knockout mice, and HSV-1–specific IFN-γ–producing CD8 T cells in WT mice receiving glutamine or no supplement.

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Reactivation of HSV-1 from trigeminal ganglia of WT and IFN-γ knockout m...
(A and B) Reactivation of HSV-1 from trigeminal ganglia (TG) of WT and IFN-γ knockout mice receiving glutamine or no supplement in their drinking water. The first experiment had 10 WT mice and 11 IFN-γ knockout mice in the glutamine group and 13 WT mice and 12 IFN-γ knockout mice in the water group (A); the second experiment had 17 WT mice and 16 IFN-γ knockout mice in the glutamine group and 15 WT mice and 16 IFN-γ knockout mice in the water group (B). See legend to Figure 1 for experimental details. (C and D) Number of HSV-1–specific IFN-γ–producing CD8 T cells per 106 lymphocytes (C) and total CD8 T cells per ganglion (D) of mice receiving glutamine or no supplement in their drinking water. The results of 4 independent experiments were pooled. Ten mice were used in the no infection group, and 30 each in the no treatment and glutamine groups. Mann-Whitney test was used for statistics; mean ± SEM is shown.