Josephine van Dongen

1 General introduction 9 Figure 1. Structure of rotavirus. 2018 @NVMM Abbreviations: dsRNA = double-stranded RNA,VP = viral protein. Clinical characteristics The clinical disease varies from asymptomatic to severe dehydration due to diarrhea, vomiting and fever. Incubation time of rotavirus is shor t, less than 48 hours.Two mechanisms explain the symptoms. First, rotavirus induces osmotic diarrhea as a consequence of cell damage, necrosis of enterocytes or villus atrophy and as a result of malabsorption. Secondly, NSP4, one of the non-structural proteins, generates secretory diarrhea and activation of the intestinal nerve system. 10 A rotavirus infection leads to fever and general malaise through pro-inflammatory cytokines, interleukins (IL-B and IL-6) and, tumor necrosis factor. The exact mechanism is not yet explained. 10 In addition, rotavirus can cause a systemic infection, rotavirus RNA has been detected in the liver, hear t, bladder, lungs, kidneys, testicles and, central nerve system. 15 Children are usually first infected between four and twenty-three months of age. 9 Presence of symptoms and severe disease course are most frequent during first infection. Immune response Immunity following rotavirus infection is primarily achieved through serum and mucosal anti- bodies against VP7 andVP4. Neutralizing antibodies offer protection against homotypic (against the same virus type) as well as against heterotypic (against a different virus type) rotavirus geno- types.This heterotypic immunity, also named cross-protection, increases with repeated rotavirus infection.The role of cellular immunity is still par tly unexplained, however virus specific CD8+ cells potentially clear the infection and protect against disease. 9,16 Rotavirus immunity is highly protective against severe symptoms, however to a lesser extent against infection.Thus, re-infec- tions with rotavirus are common and boost immunity against the virus. 17 A gradual decrease in CD4+ cells and neutralizing antibodies over time can account for incomplete immunity against re-infection. 6,13