Because we observed that MHV-68 infection leads to an increase
in the expression levels of TLR-4 and TLR-2, we next tested the
hypothesis that viral infection in early pregnancy could affect the
response to microbial products.We injected MHV-68 into pregnant
wt mice at E8.5 (early pregnancy), followed by LPS injection at
E15.5 (late pregnancy).We selected a dose of LPS that has a modest
effect on pregnancy outcome (20 mg/kg) (30). Control mice received
only vehicle or only LPS at E15.5. LPS treatment of MHV-68–
infected pregnant mice induced preterm labor/delivery in less than
24 h in all of the treated mice (Fig. 6). Anatomical examination of the
mothers showed vaginal bleeding and 100% fetal death in the
MHV-68 plus LPS-treated group (Supplemental Fig. 3). LPS administration,
without previous viral infection, induced preterm labor/delivery
in 29% of cases, and we did not observe major anatomical
changes in the mother or the fetus (Supplemental Fig. 4).