Bone marrow impairment and its relationship with the pathogenesis of Mayaro virus infection

Mayaro virus (MAYV) is an emerging arthritogenic alphavirus associated with acute febrile illness and persistent arthralgia. Although musculoskeletal manifestations are well characterized, the impact of MAYV infection on bone marrow homeostasis and hematopoiesis remains poorly understood. Here, we investigated whether acute MAYV infection disrupts the hematopoietic niche and contributes to systemic hematological alterations using a susceptible SV129 murine model. Mice were infected with MAYV and euthanized at 2, 4, 6, 8, 14 and 21 days post-infection. Animal procedures were approved by CEUA/CCS/UFRJ (protocol 037/25). Bone marrow, liver, spleen and blood samples were collected for histological and hematological analyses. Histopathological evaluation revealed extensive bone marrow injury, characterized by interstitial hemorrhage and architectural disorganization, consistent with disruption of the hematopoietic niche and associated with transient megakaryocyte alterations. These alterations were accompanied by reticulocytosis, increased red blood cell size heterogeneity and leukocyte profile changes, supporting impaired hematopoietic homeostasis during acute infection. Histological analyses further demonstrated increased splenic cellularity and hepatocyte swelling associated with the presence of myeloid progenitor cells in the liver, suggesting hematopoietic remodeling through compensatory extramedullary hematopoiesis. Viral RNA was detected in bone marrow and peripheral hematopoietic tissues, reinforcing the association between viral dissemination and tissue injury. Collectively, our findings demonstrate that MAYV infection extends beyond musculoskeletal tissues by disrupting bone marrow integrity and promoting systemic hematological disturbances. These results highlight bone marrow dysfunction as a previously neglected component of MAYV-induced disease and provide evidence that hematopoietic remodeling may represent an adaptive response to acute viral infection.