Dengue virus-induced hemorrhage in a nonhuman primate model

Area of Science:

• Virology
• Immunology
• Primatology

Background:

• A significant challenge in dengue research is the absence of an animal model that accurately reflects human dengue virus infection and its pathogenesis.
• Understanding early pathogenic events is crucial for developing effective treatments.

Purpose of the Study:

• To establish a rhesus macaque model of dengue hemorrhagic fever that mimics human disease.
• To investigate the early pathological changes and hematological alterations following dengue virus infection in non-human primates.

Main Methods:

• Intravenous inoculation of rhesus macaques (n=6) with a high dose (1 x 10^7 PFU/animal) of dengue virus serotype 2 (strain 16 681).
• Monitoring of clinical signs, blood chemistry, hematological parameters, viremia, lymphocyte counts, and platelet-monocyte/neutrophil aggregates post-infection.

Main Results:

• All inoculated macaques developed classic dengue hemorrhage within 3-5 days.
• Significant findings included elevated creatine phosphokinase, modest thrombocytopenia, neutropenia, decreased hemoglobin/hematocrit, and significantly elevated D-dimer.
• Viremia peaked early, followed by inverse T and B lymphocyte trends and bimodal patterns in platelet aggregates. Dengue virus-laden platelets were observed within monocytes.

Conclusions:

• Intravenous inoculation of rhesus macaques with a high dose of dengue virus serotype 2 successfully induces dengue hemorrhage, creating a valuable animal model.
• This model provides a platform for studying early dengue virus infection events and identifying blood components involved in disease pathogenesis.