Published on 26 November 2024

Blog Kemal Mehinagic – African swine fever

«The ASF virus fascinates me and I know it still holds many secrets I’d love to unravel».

Pathogenesis of African swine fever: interaction between virus and animal

African swine fever (ASF) is caused by a virus that is dangerous for domesticated pigs and wild boar but does not pose a direct threat to humans. A highly virulent strain of the disease was introduced into Georgia in 2007. Since then, ASF has spread to large areas of Europe and Asia and has already killed millions of animals. Despite intensive scientific efforts, we do not yet have either a treatment for ASF nor a safe vaccination. Scientists at the IVI’s high-security laboratory are researching the pig immune system and its complex interactions with the ASF virus. Other topics of study are the structure, molecular genetics and replication of the ASF virus, as well as the mechanisms by which it interacts with the host’s immune response. With a view to improving our understanding of the complex interactions between viruses and pigs, the IVI has been running its own pig breeding programme for many decades. Pigs are reared under the strictest hygiene conditions to be free of specific pathogens, so they develop what is termed a «naive» immune system. The different responses of this immune system to ASF virus infection, compared with the immune system of conventionally reared pigs, have yielded fascinating results that are described in detail in our publications.

Interview with Dr. Kemal Mehinagic

• What was the aim of your doctoral thesis?

  My thesis had two main aims: first, we wanted to understand how various host factors influence the course of disease following infection. Second, we aimed to use genetic modifications of highly virulent strains to clarify the function of individual viral genes which have functions that are still unknown, so as to gain a better understanding of this enormously complex virus. As existing methods for genetic modification of the ASF virus are very time-consuming, we also set ourselves the aim of improving those methods and possibly even developing new ones.

• What are the main findings of your dissertation?

  In several in vivo studies, we demonstrated that the pigs’ immunological and hygiene status has a marked influence on the course of disease following infection with an isolate of low to medium virulence. In the case of highly virulent ASF viruses, on the other hand, the course of disease is independent of the pigs’ immune status. But using a naturally attenuated isolate, we were able to show that our IVI specific-pathogen-free (SPF) pigs with a naive immune system experience a milder course of disease and recover far more quickly. These pigs were also much better protected against subsequent infection with a highly virulent virus than were «normal» domestic pigs reared on farms. These results emphasise the vital role of the immune system in the course of the disease and allow us to study the precise mechanisms of disease development. Last but not least, these findings are also of crucial importance for vaccine development.
  
  In the second part of my thesis, we deleted selected genes from the ASF virus genome and determined their importance and function for the virus. Among others, we identified a specific gene (called C717R), which not only plays a key role in the life cycle of the virus but also interacts strongly with the non-specific immune defences of the host cells. Such genes often provide key information on the pathways involved in antiviral immune responses, which is essential to understand for the purposes of vaccine development. In addition to these significant findings, we were able to generate a synthetic construct of the entire genome of the ASF virus. This new tool simplifies the genetic manipulation of the vast ASF genome and in future will enable us to characterise unknown genes quickly and efficiently, laying the foundations for the development of safe genetically-modified vaccines.

• To what extent will your findings help to advance research?

  In order to develop effective drugs or vaccines to fight a disease, it is crucial to understand the pathogen and the host’s immune response to it. In the case of African swine fever, unfortunately, a lot remains unknown. In my thesis I was able to further our understanding of the virus and the pigs’ antiviral immune response. This new knowledge can be used in multiple ways: notably, our findings regarding SPF pigs and the C717R gene can aid the development of potential vaccines. As is often the case in science, our research has uncovered many new questions. The complexity of the genetic modifications in particular will keep us busy for the next few years. The aim is to optimise these methods in order that genetically modified viruses can be produced quickly and effectively, and then used for further research purposes or as vaccines.

• What did you especially like about working on your thesis?

  The ASF virus fascinates me and I know it still holds many secrets I’d love to unravel. Working with «mysterious» viruses like these and solving the associated problems can be very challenging, which I personally enjoyed enormously. And working with this virus also forced me to be creative, as I often had to develop new experiments in order to answer specific questions. Besides the scientific aspects, the friendly collegial atmosphere at the IVI was very supportive. Working in a high-security laboratory was initially demanding, but all of my colleagues were very kind, co-operative and helpful. I am very pleased to have been part of this collective and delighted to have made many new friends.

• What projects do you have coming up, what are you going to do next?

  I count myself very lucky to be able to stay at the IVI and continue researching the ASF virus. As I said, there are many scientific questions that need to be answered, but I’m also looking forward to spending more time outside the lab. A doctoral thesis takes up a lot of time and energy, so your private life often gets neglected. I’m especially looking forward to spending more time with my family and taking up my hobbies again. As interesting as ASF research is, it doesn’t make you a black belt in jiu-jitsu… 😊

Publications

• The baseline immunological and hygienic status of pigs impact disease severity of African swine fever (PLOS PATHOGENS)
• In-yeast reconstruction of the African swine fever virus genome isolated from clinical samples (STAR Protocols)
• A sensitive luciferase reporter assay for the detection of infectious African swine fever virus (Journal of Virological Methods)