Fig. 1

Neurotropic virus infections of mouse cortical neurons induce SARM1 activation and increased production of cADPR. (A-C) Survival curves, weight loss and clinical scores of infected C57BL/6 mice were measured from day 0 until the end of the infection. Intracranial infections with JEV, HSV-1, RABV or mock (PBS) was performed in C57BL/6 mice (n = 6 for each mock-infected; n = 18 for each neurotropic virus infection group), respectively. Neurological disease evaluation included mortality (A), mean daily body weight loss (B), and clinical scores (C). The mock infection mice did not have any symptoms. The scores of disease severity or 30% loss of initial body weight were used as termination criteria. (D-F) The immunoblot analysis of SARM1, NMNAT2, and viral proteins in whole-cell lysates from the mouse cortex was conducted at the indicated time points following mock, JEV (D), HSV-1 (E), and RABV (F) infections using GAPDH as an internal control. (G) Representative micrographs of immunohistochemistry of brain sections stained for SARM1 from mock-, JEV (5dpi)-, HSV-1 (5dpi)-, or RABV (8dpi)-infected mice. (H and I) Mice were mock-infected or infected with neurotropic viruses at the indicated time points, respectively; the NAD⁺ (H) and cADPR (I) levels were tested in the mouse cortex, quantified as the ratio of (NAD⁺ or cADPR concentration) / (NAD⁺ or cADPR concentration of mock infected group) × 100%. (J) The day before neurotropic virus infection, mice were orally given vehicle or CD38 inhibitor 1 (twice daily). Compared with the mock-infected group, the levels of NAD⁺ and cADPR in the cortex of mice were detected after JEV (5dpi), HSV-1 (5dpi), and RABV (8dpi) infection, respectively. Individual data points are shown (n = 12 for each group). Data are expressed as means ± SEM, Student’s t test, * P<0.05, ** P<0.01,*** P<0.001