Abstract
Yellow fever virus (YFV) causes a systemic, frequently fatal infection in susceptible nonhuman primates (NHPs), which serve as important hosts and sentinels of viral circulation. However, susceptibility and pathological outcomes differ markedly between New World and Old World species. This narrative review comparatively examines the hepatic and extrahepatic histopathological spectrum of lesions associated with YFV infection in NHPs and explores their implications for pathogenesis, surveillance, conservation, and outbreak preparedness. The liver is the principal target organ, with characteristic findings including midzonal hepatocellular necrosis, Councilman bodies, microvesicular steatosis, sinusoidal congestion, hemorrhage, and relatively limited inflammatory infiltration. Extrahepatic lesions commonly involve the spleen, lymph nodes, kidneys, lungs, heart, and central nervous system, reflecting the systemic nature of severe infection. Highly susceptible Neotropical primates, particularly Alouatta spp., generally develop high viral burdens, extensive multiorgan damage, and high mortality. In contrast, many African Old World primates experience subclinical or milder infections with more limited tissue injury, possibly reflecting long-term host–virus coevolution and enhanced mechanisms of viral tolerance or control. Histopathology remains essential for investigating primate epizootics, although diagnostic accuracy improves with integration of immunohistochemistry, reverse-transcription polymerase chain reaction, in situ hybridization, and genomic methods. Standardized protocols for necropsy, sampling, lesion scoring, and reporting are needed to improve interspecies and interregional comparisons. Comparative primate pathology can strengthen early-warning surveillance, guide human vaccination strategies, support wildlife conservation, and advance integrated One Health preparedness.