*Purpose: Cytomegalovirus (CMV) viremia/infection remains a significant cause of morbidity in transplantation, especially in the undernourished population. Undernutrition and hypoleptinemia have been implicated in other infectious diseases. However, the mechanisms involved with transplant relevant viruses, such as CMV, have not been investigated. We aimed to determine the role of leptin in regulating murine CMV (mCMV) infection and T cell immunity using a murine model of undernutrition.

*Methods: C57BL/6 mice inoculated with mCMV were fed ad libitum, fasted for 48 hrs, an established surrogate for undernutrition, or fasted 48 hrs while receiving twice daily injections of murine leptin (leptin rescue). As fasting has been shown to induce hypoleptinemia, serum was collected on day 2 to confirm this in our model. Murine splenocytes were harvested at day 5 and stimulated in vitro with mCMV viral peptide. Subsequently, T cell subsets and function were examined by flow cytometry. mCMV load was quantified by qPCR.

*Results: Fasted mice had significantly higher viral loads which decreased to levels of fed mice with leptin rescue (Figure 1A; p = 0.021 and p = 0.036). Fasting induced hypoleptinemia compared to the fed state was reversed with leptin rescue (Figure 1B; p = 0.0026 and 0.027). Fasted mice had impaired mCMV-specific and CD8 effector T cell responses which improved with leptin rescue (Figure 1C; p = 0.032; Figure 1D; p = 0.036).

*Conclusions: Undernutrition and hypoleptinemia was associated with increased mCMV viremia and impaired mCMV specific T cell immunity. Leptin may be a potential therapy for improving CMV-specific T cell immunity and reducing the risk of CMV viremia in undernourished transplant recipients.

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