Gastrointestinal Structural and Functional Responses to Rotavirus Infection in the Neonatal Piglet

Abstract

Rotavirus (RV) infection is a primary cause of diarrheal diseases worldwide. RV infects villus epithelial cells, causing villus blunting and malabsorptive diarrhea. To better understand the cellular mechanisms underlying RV‐diarrhea, the time‐course of RV replication, diarrhea and intestinal structural and enzyme responses were assessed in the preclinical piglet model. Formula‐fed, colostrum‐deprived piglets were infected on d4 postpartum with group A porcine RV strain OSU (P9[7],G5). Piglets were euthanized at 0, 4, 8, and 12 h, and 1, 2, 3, 4, 6 and 8 d post‐infection (PI). RV non‐structural protein 4 mRNA expression, a marker of RV replication, increased (p<0.001) at 2d and 4d PI, but returned to baseline by 6d in the jejunum. Diarrhea occurred at 2d, peaked at 3d, began to decrease by 4d, but persisted at 8d PI compared to 0h (p<0.05). Weight gain was positive throughout the study, except a transient loss on (−0.23 kg) 2d PI. Villus height was reduced 50% from 2–8d PI (p<0.05), but crypt depth was unaffected by RV infection. Jejunal lactase activity mirrored villus height and was reduced 3‐fold from 2 to 8d PI (p<0.05), whereas sucrase activity increased 2‐fold over 0h at 2 to 8d PI (p<0.05). Thus, diarrhea persisted beyond RV replication, supporting impaired villus morphology and impaired lactose digestive capacity as the underlying causes for persistent diarrhea following RV infection. Funded by USDA AG‐05‐34505.