Search Results (4)

Viruses have evolved various strategies to evade the host innate immune system. The relationship between nairoviruses and the interferon (IFN) system is poorly understood. We investigated whether and how nairoviruses antagonize host innate immunity using Hazara orthonairovirus (HAZV) as a surrogate model for Crimean-Congo hemorrhagic fever virus. HAZV nucleoprotein (N) was found to interact with the tripartite motif-containing protein 25 (TRIM25). The N-terminal region of N protein and the C-terminal region of TRIM25 are important for their interaction. Overexpression of N protein results in weakened interaction of TRIM25 with retinoic acid-inducible gene I (RIG-I). Furthermore, K63-linked polyubiquitination of RIG-I is inhibited in the presence of N protein. Our data collectively suggest that HAZV N protein interferes with the binding of TRIM25 to RIG-I and subsequent K63-linked polyubiquitination of RIG-I, which leads to inhibition of type I IFN production. Full article

Antibody cross-reactivities between related viruses are common diagnostic challenges, resulting in reduced diagnostic specificities and sensitivities. In this study, antibody cross-reactions between neglected members of the genus Orthonairovirus—Hazara (HAZV), Dugbe (DUGV), and Nairobi sheep disease orthonairovirus (NSDV)—were investigated. Mono-specific ovine and bovine sera following experimental infections as well immunization trials with HAZV, DUGV, and NSDV were tested in homologous and heterologous virus-specific assays, namely indirect ELISAs based on recombinant N protein, indirect immunofluorescence assays (iIFA), and two neutralization test formats (plaque reduction neutralization test (PRNT) and micro-virus neutralization test (mVNT)). The highest specificities were achieved with the ELISAs, followed by the mVNT, iIFA, and PRNT. Cross-reactivities were mainly observed within the Nairobi sheep disease serogroup–but surprisingly, HAZV antibodies in PRNT did also neutralize NSDV and DUGV. In conclusion, we recommend ELISAs and mVNTs for a discriminative diagnostic approach to differentiate between these antibodies. NSDV antisera were also used in serological assays for the detection of antibodies against the human pathogen Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV). Interestingly, all CCHFV ELISAs (In-house and commercial) achieved high diagnostic specificities, whereas significant cross-reactivities were observed in a CCHFV iIFA. Previously, similar results were obtained when analyzing the HAZV and DUGV antisera. Full article

Hazara orthonairovirus (HAZV) is a tick-borne arbovirus closely related to Crimean–Congo hemorrhagic fever orthonairovirus (CCHFV). Whereas CCHFV is a biosafety level (BSL) 4 agent, HAZV is classified as BSL 2, as it is not known to cause any disease in humans. Belonging to the same serogroup as CCHFV, HAZV might act as a model which can provide a better understanding of this important zoonosis. Furthermore, the serological relatedness may cause diagnostic problems if antibodies against HAZV interfere with current CCHFV serological assays. Therefore, sheep and cattle—important natural hosts for CCHFV—were experimentally infected with HAZV to prove their susceptibility and evaluate potential antibody cross-reactivities. According to this study, neither sheep nor cattle are susceptible to experimental HAZV infections. Consequently, the HAZV infection in ruminants is clearly distinct from CCHFV infections. Sera of immunized animals weakly cross-reacted between HAZV and CCHFV in immunofluorescence and immunoblot assays, but not in commercial CCHFV ELISAs commonly used for field studies. Full article

Introduction: Crimean–Congo hemorrhagic fever (CCHF) is a severe disease of humans caused by CCHF orthonairovirus (CCHFV), a class 4 pathogen. Hyalomma ticks are the viral reservoir, and they represent the main vector. CCHFV can be transmitted to its hosts during tick blood feeding. We have previously shown that CCHFV can persistently infect Hyalomma-derived tick cell lines without any cytopathic effect. However, the mechanism allowing for the establishment of a persistent viral infection in ticks is still unknown. It has been recently reported that Hazara orthonairovirus (HAZV) can be used as a BSL-2 model virus instead of CCHFV to study viral/vector interaction. The aim of our study is to elucidate the mechanism that allows establishment of persistent CCHFV infection in ticks using HAZV as a model. Methods: We used classical and molecular methods applied to virology to characterize the establishment of persistent HAZV infection in two Hyalomma anatolicum-derived cell lines—HAE/CTVM8 and HAE/CTVM9. Results: As for CCHFV, we showed that HAZV persistently infects tick cells without any sign of cytopathic effect and that infected cells can be cultured for more than one year. The persistent infection is characterized by a low viral titer compared to the initial time points. Interestingly, short viral-derived DNA forms (vDNAs) start to be detected in parallel with the beginning of viral replication and are maintained in persistently-infected cells. Experiments with the antiretroviral drug AZT suggest that vDNAs are produced by retrotranscriptase activity. Furthermore, we collected evidence that vDNAs are not integrated and seem to be involved in the downregulation of viral replication by promoting cell survival. Conclusion: vDNA synthesis might represent a strategy to control the replication of RNA viruses in ticks, as recently demonstrated in insects, allowing for persistent infection of virus vectors. Full article