Glutamine supplementation suppresses herpes simplex virus reactivation

Area of Science:

• Immunology
• Virology
• Metabolic pathways

Background:

• Chronic viral infections like herpes simplex virus (HSV) are challenging to manage, often requiring novel therapeutic strategies.
• HSV establishes latency and can reactivate, leading to recurrent infections even with antiviral therapy.
• Virus-specific T cells are crucial for controlling HSV, and their proliferation depends on glutamine metabolism.

Purpose of the Study:

• To investigate the potential of oral glutamine supplementation in reducing the reactivation of latent herpes simplex virus.
• To explore the immunological mechanisms underlying glutamine's effect on viral reactivation, focusing on T cell responses and interferon-gamma (IFN-γ).

Main Methods:

• Supplementation with oral glutamine in latently HSV-1-infected mice and HSV-2-infected guinea pigs.
• Transcriptome analysis of trigeminal ganglia in HSV-1-infected mice treated with glutamine.
• Assessment of HSV-1 reactivation rates in wild-type (WT) and IFN-γ knockout (IFN-γ-KO) mice.
• Quantification of HSV-specific IFN-γ-producing CD8 T cells in ganglia of treated animals.

Main Results:

• Oral glutamine supplementation significantly reduced HSV reactivation in both mice and guinea pigs.
• Transcriptome analysis revealed upregulation of IFN-γ-inducible genes in glutamine-treated mice.
• Glutamine's efficacy in reducing HSV-1 reactivation was dependent on the presence of IFN-γ, as it was ineffective in IFN-γ-KO mice.
• Glutamine treatment increased the number of HSV-specific IFN-γ-producing CD8 T cells in infected ganglia.

Conclusions:

• Oral glutamine supplementation can reduce the reactivation of latent herpes simplex virus infections.
• Glutamine appears to enhance the IFN-γ-associated immune response, particularly T cell activity, contributing to viral control.
• This study suggests glutamine as a potential therapeutic agent to bolster immune defenses against chronic viral latency.