Title of the PhD Thesis: Revealing the in vitro growth-adaptive changes of Crimean-Congo hemorrhagic fever virus and conducting the first country-wide serosurveillance among humans and animals in Hungary
Deézsi-Magyar Nóra
Health Sciences
Dr. Nagy Zoltán Zsolt
Nemzeti Népegészségügyi és Gyógyszerészeti Központ, 1097 Budapest Albert Flórián út,3/a fsz.
2025-06-02 13:00:00
Public Health Science
Dr. Sótonyi Péter
Dr. Kis Zoltán
Dr. Tarján Zoltán
Dr. Kádár Béla
Dr. Kristóf Katalin
Dr. Tóth Ákos
Dr. Ostorházi _Eszter
As CCHFV shows enhanced genetic diversity that can result in the emergence of viral quasi- species, one of our aims was to determine the replication kinetics and genetic variations resulted by in vitro serial passaging in susceptible cell lines. This task is an important quality management issue, as genetic variations may lead to phenotypic changes regarding infectivity and viral fitness. In the frame of this thesis:
• We established a mutation accumulation experiment in four susceptible cell lines (Vero E6, Vero, SW13, BHK-21), followed by deep sequencing and analysis to map signature mutations.
• We found that all tested cell lines are susceptible for CCHFV, and permissivity increased due to serial passaging in Vero and BHK-21 cells.
• Growth-induced mutations emerged in a cell-line specific manner, as the applied cell lines had significant effect on the mutation variant frequency. By mapping growth- induced mutations, we were able to combine viral evolution in controlled laboratory settings with phenotypic characterization.
As Hungary stands within high evidence consensus for future CCHFV introduction and human infection, we aimed to assess CCHFV seropositivity among humans and indicator animals in the country. In the frame of this thesis:
• In total, 2700 human and 1905 serum samples taken from free-range cattle and sheep were tested for anti−CCHFV IgG antibodies using a range of commercial in-house assays. We found a total of 10 reactive samples among humans (0.44%) and 11 reactive samples (0.58%) among animals comprising 8 cattle and 3 sheep. The most affected regions were the south-central and northwestern parts of the country.
• Based on our newly generated data, Hungary is now categorized as a level 3 (high potential) country considering the risk of CCHFV introduction and future human infections.
Accordingly, a more extended surveillance is advised, especially in the affected areas, and there should be greater awareness among clinicians and other high-risk populations of the emerging threat of CCHFV in Hungary and Central Europe.
