Rotaviruses and rotavirus vaccines.

Background: Rotaviruses (RVs) are an important cause of acute gastroenteritis in infants and young children worldwide, resulting in more than 600 000 deaths per annum, mainly in developing countries. Since the 1980s, there has been intensive research on the development of RV vaccine candidates, and since 2006 two vaccines have been licensed in many countries.

Sources Of Data: The scientific literature since the 1970s has been consulted, and the results of original research carried out in authors' laboratories were used.

Areas Of Agreement: There are firmly established data on virus particle structure, genome composition, gene-protein assignment, protein-function assignment (incomplete), virus classification, the mechanisms of several steps of the replication cycle (adsorption, primary transcription, virus maturation-all partial), several mechanisms of pathogenesis, aspects of the immune response, diagnosis, illness and treatment, epidemiology and vaccine development.

Areas Of Controversy: Research on the following areas is still in full flux and in part not generally accepted: several steps of the replication cycle (mechanism of viral entry into host cells, mechanisms of packaging and reassortment of viral RNAs, morphogenesis of subviral particles in viroplasms and maturation of virus particles in the rough endoplasmic reticulum (RER) with temporary acquisition and subsequent loss of an envelope), the true correlates of protection and the long-term effectiveness of RV vaccines. GROWING RESEARCH: Recently, a system that allows carrying out reverse genetics with some of the RV genes has been established which, however, has limitations. There is intensive research ongoing, which is trying to develop better and universally applicable reverse genetics systems. There is broad research on the molecular mechanisms of the immune response and on which immunological parameter correlates best with lasting protection from severe RV disease. Research into other than live attenuated vaccines is growing.

Areas Timely For Developing Research: The establishment of better reverse genetics systems for RVs is the most important research goal for both the understanding of the molecular biology of RVs and the development of new and safe RV vaccines. The black boxes of our knowledge on aspects of RV replication (RNA packaging, RNA replication, control of reassortment and functions of the non-structural RV proteins) are under intensive research.