Herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), and varicella-zoster virus (VZV) belong to the alphaherpesvirus family and are human viral pathogens usually associated with skin lesions. HSV-1 and HSV-2 are typically causing oral or genital lesions, while VZV is the causative agent of chickenpox. After infection, the viruses establish life-long latency in sensory ganglia, and can sporadically reactivate to cause new lesions. In the case of VZV, a reactivation typically results in the development of herpes zoster (shingles). A major concern, however, is that these viruses may also cause more severe symptoms, such as post-herpetic neuralgia, fatal neurological manifestations, and severe keratitis.
Our group is analysing the complete genomes of clinical HSV-1, HSV-2 and VZV strains using advanced mathematical algorithms to
- map the evolutionary history and global genetic variability of clinical strains,
- define the evolutionary selection pressures and different genetic mechanisms, such as single nucleotide mutations and genetic recombination, that are responsible for this variability,
- define genotyping strategies for circulating strains, and,
- compare the genetic setup of viruses isolated from patients suffering from severe symptoms, with those who present mild or no symptoms, to identify viral genetic characteristics responsible for such devastating infections.
Knowledge generated during this project may increase our understanding of the virulence and immunity of these viruses. It may also help to improve our future strategies for vaccination and treatment, and to locate and estimate potential risks of using live attenuated viruses as vaccines.
Genomic signatures of pathogens
We recently found that the vast majority of viruses, bacteria and other organisms have highly specialized and optimized genomes. This optimization is based on how the organism code its genome and is often species specific, and is referred to as its genomic signature. The characteristics of a genomic signature depends of a multitude of species-specific traits related to its genetic machinery, such as reading, replicating and maintaining the genome.
In this project, we conduct basic science on genomic signatures of viruses and bacteria. The aim is to increase our understanding about the different mechanisms responsible for the origin, evolution, and spread of different pathogens, their potential to make zoonotic jumps between different host species, epidemiological and ecological fluctuations of pathogen populations, and the origin and spread of antibiotic resistant bacteria.
We are also developing methods to modify genomic signatures, aiming to construct viruses with de-optimized attenuated genomic signatures for the use as vaccines, and to optimize viral vectors used for gene therapy.