Biology subjects

Perdios, C.

Publications and source records attributed to Perdios, C..

3 recordsLinked to original sources

bioRxiv2026

Metabolic reprogramming by caloric restriction enhances acute phase virological control and reduces chronic inflammation in SIV-infected rhesus macaques

Nutrient metabolism influences HIV-1 replication, antiviral immunity, and chronic inflammation, yet is difficult to leverage for therapeutic gain. We sought to modulate metabolism in the non-human primate model of HIV-1 by caloric restriction (CR), a modality canonically known for its antiaging benefits. Four months of 30% CR was safe and resulted in broad and systemic metabolic reprogramming in healthy adult male and female rhesus macaques. Relative to that of ad libitum-fed animals, CR lowered the frequencies of target CCR5+ CD4 T cells in the gut mucosa. Upon infection with SIV, CR reduced acute phase viremia, dampened type I interferon signaling, and overall permitted a more vigorous cycling of CD8+ T cells in lymphoid tissues. CR-induced protection from SIV was associated with a robust up-regulation of glycolysis, which supported an early reduction in viremia that ultimately waned over time. During virologic suppression with antiretroviral therapy (ART), CR significantly limited gastrointestinal (GI) immune activation, improved tricarboxylic acid cycle flux, and lowered concentrations of soluble CD14 and several TNF-related molecules in plasma. Blood SIV DNA levels however were unchanged by CR, suggesting that residual GI dysfunction and inflammation can be decoupled from viral persistence. Our findings highlight that a dietary modality can limit pathology in a primate lentiviral infection. They also reveal the robust but temporally constrained nature of glycolysis in supporting an acute antiviral response. SIGNIFICANCECaloric restriction (CR) is a safe dietary intervention known to confer anti-aging and health benefits across diverse animal models. However, its application in the context of infectious diseases has yielded mixed outcomes and has largely been limited to murine systems. In this study, we therefore employed CR to examine the impact of dietary modulation on SIV infection outcomes. Our findings demonstrate that CR reduced acute-phase viremia and attenuated markers of chronic inflammation following ART, effects that were associated with distinct metabolic signatures. Collectively, these findings underscore the importance of diet and nutrition in shaping chronic viral infection outcomes, such as SIV, within a clinically relevant non-human primate model.

immunology↗

bioRxiv2025

RhCMV Expands CCR5 Memory T Cells and promotes SIV reservoir seeding in the Gut Mucosa

Cytomegalovirus (CMV) is a prevalent {beta}-herpesvirus that persists asymptomatically in immunocompetent hosts. In people with HIV-1 (PWH), CMV is associated with persistence of the HIV-1 reservoir and particular inflammatory related co-morbidities. The true causative role of CMV in HIV-associated pathologies remains unclear given that nearly all PWH are coinfected with CMV. In this study, we examined acute phase SIV dynamics in cohorts of rhesus macaques that were seropositive or -negative for rhesus CMV (RhCMV). We observed expansion of CCR5+ target CD4+ T cells in gut and lymph nodes (LN) that existed naturally in RhCMV-seropositive animals, the majority of which did not react to RhCMV lysate. These cells expressed high levels of the chemokine receptor CXCR3 and a ligand for this receptor, CXCL9, was systemically elevated in RhCMV-seropositive animals. RhCMV+ RMs also exhibited higher peak SIV viremia. CCR5 target memory CD4 T cells in the gut of RhCMV+ RMs were maintained during acute SIV and this was associated with greater seeding of SIV DNA in the intestine. Overall, our data suggests the ability of RhCMV to regulate chemotactic axes that direct lymphocyte trafficking and promote seeding of SIV in a diverse, polyclonal pool of memory CD4+ T cells.

immunology↗

bioRxiv2023

Immune Correlates of Hyperglycemia and Vaccination in a Non-human Primate Model of Long-COVID

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are major manifestations of the post-acute sequelae of SARS-CoV-2 (PASC). Our understanding of lasting glucometabolic disruptions after acute COVID-19 remains unclear due to the lack of animal models for metabolic PASC. Here, we report a non-human primate model of metabolic PASC using SARS-CoV-2 infected African green monkeys (AGMs). Using this model, we have identified a dysregulated chemokine signature and hypersensitive T cell population during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. This persistent hyperglycemia correlates with elevated hepatic glycogen, but there was no evidence of long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the AGM metabolic PASC model exhibits important similarities to human metabolic PASC and can be utilized to assess therapeutic candidates to combat this syndrome.

immunology↗