New publications & lab trip
Before the summer we published several new papers but also went on a lab trip to Zoo Zlín.
Human antibodies in Mexico and Brazil neutralizing tick-borne flaviviruses
We have contributed to the study on the possible presence of tick-borne flaviviruses infecting people in Mexico and Brazil.
Now published in Cell Reports.
Powassan virus (POWV), which causes severe neurologic illness, is a flavivirus transmitted by ticks in temperate regions of the Northern hemisphere. We find serologic neutralizing activity against POWV in individuals living in Mexico and Brazil. Monoclonal antibodies P002 and P003, which were derived from a resident of Mexico (where POWV is not reported), neutralize POWV lineage I by recognizing an epitope on the virus envelope domain III (EDIII) that is shared with a broad range of tick- and mosquito-borne flaviviruses. Our findings raise the possibility that POWV, or a flavivirus closely related to it, infects humans in the tropics.
Brno loanvirus (BRNV) in bats inhabiting the urban area of Brno, Czech Republic
Bats are known reservoirs of various emerging pathogens, and have recently been found to host a novel hantavirus, named Brno loanvirus (BRNV), from the Mammantavirinae subfamily (family Hantaviridae, order Bunyavirales). Here we report BRNV detection in bats from the urban area of Brno, Czech Republic in March 2022. Specifically, we uncovered a high prevalence of BRNV (8.8%, 5/57) among hibernating bats (Nyctalus noctula) in urban area, which poses a risk of human exposure. The positive bats included adult females (3/9 positive), a juvenile female (1/32 positive), and an adult male (1/6 positive). All 10 juvenile males were negative. We used RT-qPCR to quantify the BRNV RNA levels in various bat organs, which yielded positive results for viral RNA in organs, including the kidneys, heart, spleen, brain, liver, lung, and gut, and in body cavity fluid.
Now published in Infections, Genetics and Evolution.
Influence of adjuvant type and route of administration on the immunogenicity of Leishmania-derived tick-borne encephalitis virus-like particles - A recombinant vaccine candidate
We contributed to the study, where we explored the impact of adjuvants (AddaS03™, Alhydrogel®+MPLA) and administration routes (subcutaneous, intramuscular) on the immune response. The combination of Leishmania-derived TBEV VLPs with Alhydrogel® and MPLA via intramuscular administration emerged as a highly promising prophylactic vaccine candidate, eliciting a robust, balanced immune response with substantial neutralization potential.
Published in Antiviral Research.
Unraveling the Role of Human Microglia in Tick-Borne Encephalitis Virus Infection: Insights into Neuroinflammation and Viral Pathogenesis
In this study, published in Microbes and Infections, we investigated the susceptibility of human microglia to TBEV, focusing on productive infection and different immune responses of different viral strains. We investigated primary human microglia and two immortalized microglial cell lines exposed to three TBEV strains (Hypr, Neudörfl and 280), each differing in virulence. Our results show that all microglia cultures tested support long-term productive infections, regardless of the viral strain. Moreover, electron tomography revealed substantial ultrastructural changes in the infected microglia, despite the absence of cytopathic effects. These findings underscore the susceptibility of human microglia to TBEV and reveal strain-dependent variations in viral replication and immune responses, highlighting the complex role of microglia in TBEV-induced neuropathology.
The structure of immature tick-borne encephalitis virus supports the collapse model of flavivirus maturation
We participated in the study describing structures of three immature tick-borne encephalitis virus (TBEV) isolates - Hypr, Neudoerfl and Kuutsalo-14. Our atomic models of the major viral components, the E and prM proteins, indicate that the pr domains of prM have a critical role in holding the heterohexameric prM3E3 spikes in a metastable conformation. Destabilization of the prM furin-sensitive loop at acidic pH facilitates its processing. The prM topology and domain assignment in TBEV is similar to the mosquito-borne Binjari virus, but is in contrast to other immature flavivirus models. These results support that prM cleavage, the collapse of E protein ectodomains onto the virion surface, the large movement of the membrane domains of both E and M, and the release of the pr fragment from the particle render the virus mature and infectious. Our work favors the collapse model of flavivirus maturation warranting further studies of immature flaviviruses to determine the sequence of events and mechanistic details driving flavivirus maturation.
The study is recently published in Science Advances.
At the end of May, we organized a trip to Zlín Zoo, where we enjoyed the beautiful, almost summer-like weather. On the way back to Brno, we visited the highest building in Zlín and enjoyed the view of the whole city, which is associated with the Baťa shoe company.
