Longitudinal analysis of rhesus macaque metabolome during acute SIV infection reveals disruption in broad metabolite classes

Despite significant advances in antiretroviral therapy and pre-exposure prophylaxis, HIV remains a global challenge. Understanding the underlying immune mechanisms is critical for improving HIV control and therapeutic development. Cellular metabolism represents a crucial yet underappreciated area of immune system function. Metabolite availability and metabolic pathway preferences directly influence the functional response capacity of immune cells and are highly dysregulated during HIV infection. To further the understanding of metabolic impacts of HIV infection, we utilized cutting-edge mass spectrometry-based metabolome interrogation to measure over 500 metabolites using an acute simian immunodeficiency virus infection model in rhesus macaques. Our comprehensive analysis provides insights into the dynamic metabolic landscape throughout early infection, revealing both known and novel metabolic signatures. These findings enhance our understanding of the complex interplay between metabolism and immunity in lentiviral infections, potentially informing new strategies for early detection, prevention, and treatment of HIV.