Factors at the Intrahuman Barrier

Our primary research studies on the intrahuman barriers aim to identify key factors that determine the ability of viruses and bacteria to infect and adapt to replication in humans. The intrahuman barrier studies are divided into four studies as summarised below.

The role of pathogen evolution in adaptation to new hosts.  Improving our understanding of both the genetic and antigenic variation among specific zoonotic RNA viruses and zoonotic bacteria – including pathogenic E. coli – is essential to improving the prediction of whether pathogens are able to overcome barriers in the emergence chain. We hypothesize that the selection acting on a pathogen to escape from specific immunity could, as a side-effect, change the receptor-binding specificity of the attachment protein, and thus enable a pathogen to cross the species barrier to humans. For the EHEC outbreak strain O104:H4, our studies will lead to a broader understanding of the genomic changes that might be responsible for its increased virulence and ability to spread.

Model pathogens studied: Lagos Bat virus, Duvenhage virus, SARS Coronavirus, Influenzavirus A, Streptococcus suis, Escherichia coli.

The critical pathogen and host factors for zoonotic viruses to cross the intrahuman barriers. A major intrahuman barrier probably involves those factors of the host cell that co-operate with replicative virus enzymes and virus proteins during morphogenesis and egress. By identifying the most critical factors restricting virus entry, replication, and egress for large taxa, we will investigate whether (and which of) these factors can be experimentally characterized by surrogate assays (cell- and pseudotype-based, at medium and high throughput). In this way, we hope to achieve experimentally-based characterizations of the human-directed replicative potential of a larger diversity of reservoir-borne viruses.

Model pathogens studied: Lagos Bat virus, Hantavirus, Rift Valley Fever virus, Japanese Encephalitis virus, Marburg virus, Ebolavirus, Henipahvirus, SARS Coronavirus, Influenzavirus A, Gouleakovirus, Nouane virus.

Research on pathogen and host factors in zoonotic bacteria crossing the intrahuman barriers. By determining host- and pathogen-specific factors that increase Mycobacterium bovis transmission to humans, we will be able to identify pathogen strains with higher pandemic potential and molecules that could be used for early diagnostic, prevention and treatment of tuberculosis. Identification of putative invasion routes and associated bacterial virulence and host susceptibility determinants of Streptococcus suis will improve our understanding of pathogen and host factors that contribute to the emergence of food-borne zoonotic pathogens. By use of animal models for Lyme disease, we will improve our understanding of the transmission of Borrelia burgdorferi and the role of strain variation and vector saliva on organ tropism and pathogenicity.

Model pathogens studied: Mycobacterium bovis, Streptococcus suis, Borrelia burgdorferi

Research on the human immune response to zoonotic pathogens.  It is known that virulence factors in zoonotic viruses and bacteria counteract parts of the immune control in the natural reservoir, generating a balance between pathogen and host. If these virulence factors are also active in humans, where population immunity is absent, these pathogens may become virulent, replicatively active, and eventually, epidemic. In this research, we will gain a better understanding of how (zoonotic) pathogens evade innate and specific immunity in humans compared to the natural reservoir. This will help to predict the zoonotic and pandemic potential of these zoonotic pathogens. Studies on pathogenic E. coli will identify key factors determining the degree of host adaptation of newly emerging EHEC O104:H4 outbreak strain as compared to STEC persistently infecting bovine and conventional human EHEC.

Model pathogens studied: Hantavirus, Duvenhage virus, Marburg virus, Ebolavirus, Henipahvirus, SARS Coronavirus, Streptococcus suis, Escherichia coli.