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Characterisation of the zoonotic potential of poultry rotaviruses (Rotaviren)

03/2016-02/2019

This third-party funded project is conducted in the framework of the BfR research programme on exposure estimation and assessment of biological risks.

DFG grant number: JO 369/4-3

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Project description:

Rotaviruses are a major cause of gastroenteritis in humans and many animal species. Two vaccines, which are mainly based on human rotaviruses, are currently used worldwide for prevention of severe rotavirus disease in young children. Transmission of rotaviruses from mammalian animals to humans has been repeatedly described. In contrast, it is unclear whether rotaviruses of birds can be transmitted to humans and whether this can result in the creation of mixed viruses. The investigations in this project should clarify this question.

As a result of the first phase of the project, we could show that rotaviruses are broadly distributed among poultry and that a high number of different types exist. For the first time, the whole genome sequences of rotaviruses belonging to avian rotavirus groups D, F and G were determined, showing that they are only distantly related to human rotaviruses. However, the analyses also show that these viruses may be able to create mixed viruses through reassortment with human rotaviruses of group A or B. Additionally, our genome analysis of a rotavirus from a pheasant suggests that this virus contains a genome segment from a mammalian rotavirus, indicating a mutual transmission of mammalian and avian rotaviruses in nature. Laboratory experiments showed that human and avian rotaviruses could infect cell cultures of both hosts. Using a novel helpervirus-dependent reverse genetics system, we recently engineered a replication-competent mixed virus from chicken and monkey rotaviruses, which should be characterised now.

In the proposed second period of the project, the experiments for the specific engineering of avian/mammalian mixed rotaviruses should be continued using double infections of cell cultures. The recently engineered mixed virus will be characterised in detail. In addition to its ability for replication in mammalian and avian cells, the reactivity with antisera directed against its parent viruses will be assessed. This possibly will allow assessing the efficiency of the currently used vaccines against such mixed viruses. The general use of the applied helpervirus-dependent reverse genetics system for directed engineering of rotavirus reassortants should be tested. By doing so, antigenetic variants which have not replicated in cell culture so far may be propagated and provided as antigens. The experiments to establish a helpervirus-independent reverse genetics system should be continued in order to enable the investigation of the effects of specific changes in the genome of the viruses on their host spectrum and ability of replication.

The results will help to identify the transmission pathways of rotaviruses, to record their variability and to elucidate the involved molecular mechanisms. In this way, the risk of transmission of avian rotaviruses to humans and of development of novel mixed viruses can be estimated, thus contributing to the development of broadly efficient vaccines.

Project partners:

• National Institute of Allergy and Infectious Diseases, USA
• The Institute for Integrative Biology of the Cell, France
• Freie Universität Berlin, Germany

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