Role of antibody-dependent enhancement in DENV-infected Wistar rats as a dengue murine model

Abstract

AbstractPreclinical studies for discovering and developing a drug for a disease involve utilizing animals as experimental subjects. The search for an effective and efficient murine model of dengue virus (DENV) infection is ongoing to support further scientific updates. This study aimed to explore the suitability of Wistar rats as a murine model for DENV infection. Twenty-four Wistar rats (male sex, 2-3 months old, 200-300 grams weight) were randomly divided into four groups (n=6 per group): control group (no infection), SC-Group (DENV-2 s.c.), IV-Group (DENV-2 i.v.), and ADE-Group (DENV-3 i.p. twice and DENV-2 i.v. once). Inactive 0.2 mL of 1011FFU/mL DENV-3 were injected on days -14 and -5. Active 0.2 mL of 5 x 108FFU/mL DENV-2 were injected on day 0. Rectal temperature was measured on day 0 until 6. NS1 antigen tests were carried out from the viral medium on days -14, -5, and 0 and from the blood serum samples on day 4. Hematological parameters (leukocytes, hemoglobin, hematocrits, and platelets) were analyzed on days 0, 4, and 6. Biochemical parameters (albumin, ALT, and AST) were analyzed on day 6. SC-Group showed significant increases in the temperature from day 0 to day 1 (p=0.028). IV-Group showed significant increases in the temperature from day 0 to day 1 (p=0.007), day 2 (p=0.002), and day 3 (p=0.006). There were significant temperature increases on day 1 (p=0.047), day 2 (p=0.009), and day 3 (p=0.001) compared to the control group. ADE-Group had a mortality rate of 33.3%, lusterless and ruffled hair coat, and several hemorrhagic manifestations. ADE-Group also showed significant increases in the temperature from day 0 to day 2 (p=0.043) and day 3 (p=0.038). There were significant temperature increases on day 1 (p=0.048), day 2 (p=0.002), day 3 (p=0.000), and day 4 (p=0.004) compared to the control group. Leukocytes in the ADE-Group showed significant decreases from day 0 to day 6 (p=0.021). ALT (p=0.033) and AST (p=0.011) of the ADE-Group also showed significant increases compared to the control group. DENV infection through an induction method adapted from the antibody-dependent enhancement mechanism shows the most severe clinical manifestations and laboratory findings compared to other induction methods in Wistar rats.