Rotavirus is the commonest cause of severe diarrhoea in infancy and childhood. It is a ubiquitous double-stranded RNA virus transmitted by the faecal–oral route. Observations by an Australian research group have linked rotavirus infection to the timing of appearance of islet autoantibodies in first degree relatives of a child with type 1 diabetes. Sequence homology has been proposed between two peptide sequences in VP7, a highly immunogenic structural viral glycoprotein, and the islet antigens IA2 and GAD65. These sequences have been shown to bind to HLA Class II molecules conferring susceptibility to type 1 diabetes on human T cells and to elicit cross-reacting T cell proliferative responses to both viral peptide and islet autoantigens. These observations offer a theoretical basis for a possible involvement of rotavirus in the pathogenesis of type 1 diabetes, but the epidemiological basis for this suggestion requires independent confirmation.

Introduction to Rotavirus

Rotavirus in a child's faeces
Rotavirus in a child's faeces
Rotavirus is a double-stranded RNA virus in the family Reoviridae, and accounts for up to 50% of hospitalisations for severe diarrhoea in infants and children. It has been estimated that every child in the world has been infected at least once before the age of 5.[1] There are five species of the virus, referred to as Rotavirus A to E. Rotavirus A is responsible for >90% of infections in humans. The virus is transmitted by the faecal–oral route. It infects and damages the cells that line the small intestine and causes gastroenteritis, and can be lethal in young children. Since immunity develops following exposure to each strain, subsequent infections are less severe, and adults are rarely affected with any severity.1

Possible role in type 1 diabetes

A temporal association between rotavirus infection and the first appearance of islet autoantibodies was reported in the Australian BabyDiab Study in 2000.[2] Several supporting observations suggested a possible causal relationship:

  • Rotavirus can invade the pancreas, causing acute pancreatitis, and can be grown in human beta cells in culture.
  • There is sequence homology between peptide sequences in the structural glycoprotein VP7, which is present on the outer surface of the virion and highly immunogenic, and two islet autoantigens. The peptide sequence aa40–52 is similar to the sequence aa805–817 in IA2, and the viral sequence aa16–28 resembles aa115–128 in GAD65.
  • These peptides and their islet antigen counterparts have been shown to bind to HLA Class II molecules conferring susceptibility to type 1 diabetes, and to induce proliferative responses in T cells.[3]


Interpretation of these preliminary observations illustrates some of the many difficulties involved in linking a virus to the pathogenesis of type 1 diabetes. Coincidence in timing between a very common viral infection and the first appearance of detectable autoantibody levels in the circulation is suggestive, yet might arise by chance, and does not in itself imply causation. Other groups involved in prospective studies of the natural history of progression to diabetes in high risk relatives have yet to replicate these findings. Equally, the molecular studies indicate a possible mechanistic link between immune responses to viral infection and islet antigens, but further studies will be needed to establish whether one of the roads to type 1 diabetes leads via rotavirus infection.


  1. ^ Bernstein DI. Rotavirus overview. Pediatr Infect Dis J 2009;28 (3 Suppl):S50–S53

  2. ^ Honeyman MC et al. Association between rotavirus infection and pancreatic islet autoimmunity in children at risk of developing type 1 diabetes. Diabetes 2000;49:1319–24

  3. ^ Honeyman MC et al. Evidence for molecular mimicry between human T cell epitopes in rotavirus and pancreatic islet autoantigens. J Immunol 2010;184:2204–10


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