Approximately 60% of people in the United States are infected with herpes simplex virus type 1 (HSV-1) and 20% with HSV-2. Prophylactic therapy with acyclovir or valacyclovir reduces the rate of cold sore (herpes labialis) recurrences by 40% to 60% and the rate of genital herpes reactivation by 70% to 80%. Thus, other approaches to reduce reactivation of HSV are needed. Control of reactivation of HSV correlates with virus-specific T cells. Increased T cell function might reduce virus reactivation. Nutrients, including glucose and certain amino acids, are critical for T cell activation. Activated T cells require increased metabolism of glutamine for proliferation, and deprivation or inhibition of synthesis of these glutamine reduces T cell proliferation. We found that supplementation with oral glutamine reduced virus reactivation in latently HSV-1-infected mice and HSV-2-infected guinea pigs. Analysis of host cell gene expression of trigeminal ganglia from latently HSV-1-infected, glutamine-treated WT mice showed upregulation of several IFN-gamma-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-gamma-KO mice. Mice treated with glutamine also had higher numbers of HSV-specific IFN-gamma-producing CD8 T cells in latently infected ganglia. Thus, glutamine may enhance the IFN-gamma-associated immune response and reduce the rate of reactivation of latent virus infection.

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43
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2017
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Cohen, Jeffrey I (2018) Author Correction: New activities for old antibiotics. Nat Microbiol 3:844
Cohen, Jeffrey I (2018) New activities for old antibiotics. Nat Microbiol 3:531-532
Bollard, Catherine M; Cohen, Jeffrey I (2018) How I treat T-cell chronic active Epstein-Barr virus disease. Blood 131:2899-2905
Sadaoka, Tomohiko; Schwartz, Cindi L; Rajbhandari, Labchan et al. (2018) Human Embryonic Stem Cell-Derived Neurons Are Highly Permissive for Varicella-Zoster Virus Lytic Infection. J Virol 92:
Cohen, Jeffrey I (2018) Herpesviruses in the Activated Phosphatidylinositol-3-Kinase-? Syndrome. Front Immunol 9:237
Coghill, Anna E; Bu, Wei; Hsu, Wan-Lun et al. (2018) Evaluation of Total and IgA-Specific Antibody Targeting Epstein-Barr Virus Glycoprotein 350 and Nasopharyngeal Carcinoma Risk. J Infect Dis 218:886-891
Burbelo, Peter D; Gunti, Sreenivasulu; Keller, Jason M et al. (2017) Ultrarapid Measurement of Diagnostic Antibodies by Magnetic Capture of Immune Complexes. Sci Rep 7:3818
Cohen, Jeffrey I (2017) GATA2 Deficiency and Epstein-Barr Virus Disease. Front Immunol 8:1869
Wang, Kening; Hoshino, Yo; Dowdell, Kennichi et al. (2017) Glutamine supplementation suppresses herpes simplex virus reactivation. J Clin Invest 127:2626-2630
Liu, XueQiao; Cohen, Jeffrey I (2016) Epstein-Barr Virus (EBV) Tegument Protein BGLF2 Promotes EBV Reactivation through Activation of the p38 Mitogen-Activated Protein Kinase. J Virol 90:1129-38

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