Experimental Yellow Fever in Squirrel Monkey: Characterization of Liver In Situ Immune Response

Area of Science:

• Veterinary Virology
• Primate Pathology
• Immunology

Background:

• Non-human primates, like squirrel monkeys, are crucial in yellow fever virus (YFV) transmission cycles in endemic regions.
• Understanding YFV pathogenesis in susceptible hosts is vital for disease control.

Purpose of the Study:

• To investigate the virological, histopathological, and immunohistochemical changes in the livers of squirrel monkeys experimentally infected with YFV.
• To elucidate the immune response and cellular mechanisms involved in YFV-induced liver injury.

Main Methods:

• Experimental YFV infection in squirrel monkeys (Saimiri spp.).
• Monitoring of viremia, liver histopathology (apoptosis, necrosis, steatosis, edema), and immunohistochemistry for immune markers (S100, CD11b, CD57, CD4, CD20, endothelial markers, cytokines like IFN-γ, TNF-α, IL-35, IL-17).

Main Results:

• Viremia persisted for up to 30 days post-infection, with YFV tropism for the liver's middle zone (Z2).
• Affected livers exhibited jaundice, petechiae, apoptosis, necrosis, steatosis, and cellular edema.
• Immune response involved diverse cell populations and cytokines, with severe lesions linked to excessive pro-inflammatory cytokine production (IFN-γ, TNF-α) and adhesion molecule expression in Z2.
• Intense immunostaining of endothelium and bile ducts suggested their role in liver damage.

Conclusions:

• Squirrel monkeys are susceptible to YFV, developing significant liver pathology.
• The study highlights the complex immune response and the critical role of endothelial damage and cytokine dysregulation in YFV liver pathogenesis.