CXCL9 and CXCL10 Expression are Critical in Resistance to Genital Herpes Simplex Virus Type 2 (HSV-2) Infection (43.15)

Abstract The relevance of CXCL9 and CXCL10 expression in protection against genital herpes simplex virus type 2 (HSV-2) infection was investigated using mice deficient in CXCL9 (CXCL9−/−) or CXCL10 (CXCL10−/−) along with C57BL/6 wild type (WT) mice. Progesterone-sensitized mice infected with 2,000 pfu HSV-2 intravaginally were exsanguinated at times post infection (p.i.), and the vaginal tissue (VG), spinal cord (SC), and brain stem (BS) were removed and assayed for virus titer, leukocytes infiltration, and cytokine/chemokine content. CXCL10−/−, but not CXCL9−/− or WT mice were found to possess HSV-2 in the SC at day 3 following infection. By day 7 p.i., CXCL9−/− and CXCL10−/− mice harbored significantly more virus in the SC and the BS compared to WT mice. The increase in virus titer in the BS and SC of the chemokine deficient mice correlated with a decrease in NK cell mobilization to the nervous system at day 5 p.i. and CD8+ T cells mobilization at day 7 p.i. In addition, there was a noticeable increase in vaginal inflammation (measured by cytokine/chemokine levels and leukocyte infiltration) in the CXCL10−/− mice compared to the WT or CXCL9−/− mice. Antibody-mediated depletion of NK cells resulted in an increase in HSV-2 levels in the vagina, SC, and BS of wild type mice suggesting these cells contribute to resistance to infection. This work supported by AI053108.