An interview with lead author Penelope Koraka, sharing her latest insights on Rabies, recently published in Frontiers in Microbiology: Analysis of Mouse Brain Transcriptome After Experimental Duvenhage Virus Infection Shows Activation of Innate Immune Response and Pyroptotic Cell Death Pathway [March, 2018]
Penelope is employed at Viroclinics Biosciences as Manager Clinical Virology Services. Her expertise includes work with tropical and neglected viruses such as Dengue, Chikungunya and Rabies. In the role of Study Director (Respiratory) Viral Infections (other than Influenza), she leads the operational side of virus studies for major pharma and biotech clients, including laboratory management. She also supports the process of transitioning novel assays from the R&D to the clinical function. Penelope holds a PhD in Virology from the medical faculty of the Erasmus University, Rotterdam.
Building expertise in the field of tropical viruses does not happen overnight. At what point in your career did you develop an interest in Rabies?
Penelope: “Let’s look at the bigger picture here. My interest in tropical viruses is part of a personal desire that started very early in my life. During childhood, I was interested in the medical field. I always imagined myself in a profession in which I would make a major contribution to the health and wellbeing of humans. I left my home country, Greece, to pursue a career as a trainee technician at the Erasmus Medical Centre in 1997. In this period, I developed a profound interest in virology. It turned my knowledge journey to research driven studies. I finished a MSc in Immunology of Infectious Diseases followed by a PhD in Virology. During my studies I embarked on a research role, focused on dengue vaccines. I quickly became interested in the gap of knowledge that exists in the field of tropical diseases. In contrast to viruses like Influenza, little is known about tropical viruses. For me as a researcher lyssa viruses like Rabies (RABV) are particularly interesting in the sense that they add an additional ‘research dimension’. Rabies affects the neurological pathway system of humans (and other mammals) and specifically the brain function. So being a virologist is not enough to study Rabies, you also need to gain in-depth knowledge about neurology. In my opinion the science community only revealed the tip of the iceberg in relation to Rabies. There is still a major knowledge gap, which stimulates my scientific drive”.
So, as a scientist you must tackle a lot of difficulties. Can you elaborate on your biggest challenge?
Penelope: “This happened during my early post doc years. I remember, I was given an aliquot of a sample with very little unknown virus in it. My task was to create an early phase experiment to produce valuable (genomics) data. I had to start from scratch and came up with a custom designed assay work flow, consisting of culture, PCR, Neutralizing Antibodies and sequencing. But with research blood in my veins, I do not mind a challenge. In fact, I am very grateful for the ‘single aliquot experience’. I have learned to think outside the box, which is essential in virology, since every new research project forms a unique challenge”.
How does your recent research contribute to the current Rabies knowledge gap?
Penelope: “From a scientific point of view, the gap consists of a lack of pathogenic knowledge of rabies caused by other lyssa viruses. We have used an approach to characterize the host response to Duvenhage virus infection and compared it with responses observed during RABV infection by gene expression profiling of mouse brains with the respective infections. We found several indicators, suggesting a strong antiviral response. Furthermore, evidence was provided that in the absence of significant neuronal apoptotic death, cell death of neurons is mediated via the pyroptotic pathway in the infection. The major finding of our studies may be that infection of mice with lyssaviruses results in a gene expression profile that involves pyroptosis. This was supported by research data indicating that pyroptosis is a pathogenic mechanism of lyssa-virus induced encephalitis. So in essence we narrowed the scientific gap by zooming in on the causal relationships between Rabies and other lyssa viruses.”
Rabies infections are found in more than 150 countries. 95% of human deaths occur in the Africa-Asia region1.
How far are we from an antiviral specifically designed to tackle Rabies?
Penelope: “Currently, no treatment exists for Rabies. The scientific community is still in the exploratory preclinical phase of research. It is almost impossible to predict when we are ready to translate all the pre-clinical work into a solid clinical case study. It is likely that this process will take many years. I think the key here is to set up cooperation frameworks with a broad range of stakeholders in the field, including the pharmaceutical corporations, the scientific community, NGOs and strategic alliances. As scientists we hope that we can move this group of stakeholders towards the launch of an antiviral for Rabies. Getting this whole process in motion is challenging to say the least. However we are scientists, so we’re certainly not afraid of any challenges.
What is your appeal to the research and pharmaceutical communities in relation to Rabies research?
Penelope: “Getting rid of dogmas is the advice here. Far too often we are dragged into ‘compartmentalized’ preconceptions fueled by rules, regulations and industry norms. For instance, we all take it for granted that certain types of vaccines are used for specific viral targets. We need to keep asking ourselves questions like: why not focus on adjuvant vaccines for Rabies? Benefits include a reduction of antigen amount and vaccine doses. Positive implications might also include cost reductions of vaccines for end users in specific world regions. I would also like to highlight the importance of childhood immunization programs as a comprehensive approach to support Rabies eradication”.
To conclude, there is much work to be done. We are only at the beginning phase of researching Rabies. At Viroclinics Biosciences we contribute to the need of understanding the underlying mechanisms that cause Rabies. With a dedicated team of (pre)clinical scientists, BSL3 facilities and specific mouse models for Rabies we certainly bring expertise to the table.
1[WHO Rabies Factsheet, published on: www.who.int, Sept. 2017]
- Please do not hesitate to contact Penelope Koraka for further discussion: firstname.lastname@example.org or via Linked In
- Please visit the Pubmed Section of our website for more relevant research articles.
- The open access article ‘Analysis of Mouse Brain Transcriptome After Experimental Duvenhage Virus Infection Shows Activation of Innate Immune Response and Pyroptotic Cell Death Pathway’ can be downloaded Here.