PhD defence N.C. (Nele) Villabruna

Dissertation in short:

Noroviruses are the most common viral cause of acute gastroenteritis, causing an estimated 684 million infections and over 200’000 deaths yearly worldwide. Based on sequence similarity, noroviruses are categorized into >40 genotypes of which some are common and others are only sporadically detected. In addition, new genotypes and new recombinants emergence frequently. In this thesis we investigated potential sources of norovirus diversity.

In part one, we investigated animals as a potential norovirus reservoir. Human norovirus sequences have been found in various animals and we used phylogenetic methods to compare these sequences with norovirus sequences found in humans. Most sequences were very similar, arguing against long term circulation in animals. However, there were some noroviruses that had accumulated mutations, potentially indicating adaptation to the host. We could also show that noroviruses can attach to intestinal tissues of the same species as well as species in which no noroviruses have been detected before. This could indicate a broad norovirus host range.

In part two, we investigated norovirus circulation in humans. Using serology, we investigated norovirus exposure in ~280 children and demonstrated which noroviruses most frequently infect young children. We moreover investigated norovirus evolution during chronic norovirus infection in immunocompromised individuals and showed that these viruses change with regards to their antigenic and binding properties.

In part three, we investigated a potential molecular mechanism for norovirus emergence. We tested the polymerase activity of different noroviruses and demonstrated that polymerases do differ in their activity but that this alone does not explain the differences in norovirus abundance.