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Feline infectious peritonitis (FIP) caused by feline coronavirus (FCoV) is a common dis-ease in cats, fatal if untreated, and no effective treatment is currently legally available. The aim of this study was to evaluate efficacy and toxicity of the multi-component drug Xraphconn® in vitro and as oral treatment in cats with spontaneous FIP by examining survival rate, development of clinical and laboratory parameters, viral loads, anti-FCoV antibodies, and adverse effects. Mass spectrometry and nuclear magnetic resonance identified GS-441524 as an active component of Xraphconn®. Eighteen cats with FIP were prospectively followed up while being treated orally for 84 days. Values of key parameters on each examination day were compared to values before treatment initiation using linear mixed-effect models. Xraphconn® displayed high virucidal activity in cell culture. All cats recovered with dramatic improvement of clinical and laboratory parameters and massive reduction in viral loads within the first few days of treatment without serious adverse effects. Oral treatment with Xraphconn® containing GS-441524 was highly effective for FIP without causing serious adverse effects. This drug is an excellent option for the oral treatment of FIP and should be trialed as potential effective treatment option for other severe coronavirus-associated diseases across species.

In 2018, West Nile virus (WNV) broke out for the first time in Germany, with continuation of the epidemic in 2019, involving birds, horses and humans. To identify vectors and characterize the virus, mosquitoes were collected in both years in zoological gardens and on a horse meadow immediately following the diagnosis of disease cases in birds and horses. Mosquitoes were identified and screened for WNV by qRT-PCR, with virus-positive samples being sequenced for the viral envelope protein gene. While no positive mosquitoes were found in 2018, seven mosquito pools tested positive for WNV in 2019 in the Tierpark (Wildlife Park) Berlin. The pools consisted of Cx. pipiens biotype pipiens (n = 5), and a mixture of Cx. p. biotype pipiens and Cx. p. biotype molestus (n = 2), or hybrids of these, and were collected between 13 August and 24 September 2019. The virus strain turned out to be nearly identical to two WNV strains isolated from birds diseased in 2018 in eastern Germany. The findings represent the first demonstration of WNV in mosquitoes in Germany and include the possibility of local overwintering of the virus.

West Nile virus (WNV) is a mosquito-borne flavivirus mainly circulating in eastern Germany, causing annually reoccurring epizootics in the avifauna as well as sporadic infections in humans and horses. WNV is closely-related to Usutu virus (USUV) and tick-borne encephalitis virus (TBEV) and co-infections thereof are becoming more frequent. To not solely be dependent on the monitoring of wild birds and horses the availability of alternative sentinel species is advantageous. The study examined the seroprevalence of WNV antibodies (Abs) in eastern Germany in readily available species: dogs, wild boars, sheep, and goats. An NS1-ELISA was implemented to ease future differentiation of cross-reacting flavivirus Abs with a sensitivity of 92.3 and 90.9% for dog and wild boar sera, respectively. Flavivirus seroprevalences were the highest in wild boars with 42.03%, followed by dogs with 7.86%, and small ruminants with 1.57%. In the wild boars and dogs, WNV Abs were most frequent (17.64 and 3.90%, respectively) while seroprevalences in small ruminants and of USUV were lower. The NS1-ELISA is cost-efficient and reliable in monitoring WNV Abs in dogs as well as wild boars and the combined testing thereof could be ideal in detecting semi-urban transmission events prior to wildlife-human spill overs.

Hepatitis E virus (HEV) poses a significant risk to human health. In Europe, the majority of HEV infection are caused by the zoonotic genotype 3 (HEV-3), which can cause chronic hepatitis E in immunocompromised patients and those with pre-existing liver disease, and may eventually develop into fatal liver cirrhosis. In this study, we examined the effectiveness of a monoclonal antibody (MAb) treatment strategy using a well established HEV-3 pig model with intravenous infection. For this purpose, nine MAbs raised against the viral capsid protein were generated and the neutralizing activities were compared using in vitro assays. The antibody with the highest neutralizing activity, MAb 5F6A1, was selected for an in vivo study in pigs infected with HEV-3. Following the initial infection of pigs with HEV-3, MAb 5F6A1 was administered intravenously one and seven days post-infection. The results suggest MAb 5F6A1 significantly reduced viremia and virus shedding in pigs infected with HEV-3. This study provides significant insight into the dynamics of HEV infection in pigs and highlights the efficacy of MAb based therapy as an option for treating HEV in porcine hosts and, potentially, humans.

Background Usutu virus (USUV) is a rapidly spreading zoonotic arbovirus (arthropod-borne virus) and a considerable threat to the global avifauna and in isolated cases to human health. It is maintained in an enzootic cycle involving ornithophilic mosquitoes as vectors and birds as reservoir hosts. Despite massive die-offs in wild bird populations and the detection of severe neurological symptoms in infected humans, little is known about which mosquito species are involved in the propagation of USUV. Methods In the present study, the vector competence of a German (i.e. “Central European”) and a Serbian (i.e. “Southern European”) Culex pipiens biotype molestus laboratory colony was experimentally evaluated. For comparative purposes, Culex torrentium , a frequent species in Northern Europe, and Aedes aegypti , a primarily tropical species, were also tested. Adult female mosquitoes were exposed to bovine blood spiked with USUV Africa 2 and subsequently incubated at 25 °C. After 2 to 3 weeks saliva was collected from each individual mosquito to assess the ability of a mosquito species to transmit USUV. Results Culex pipiens biotype molestus mosquitoes originating from Germany and the Republic of Serbia and Cx. torrentium mosquitoes from Germany proved competent for USUV, as indicated by harboring viable virus in their saliva 21 days post infection . By contrast, Ae. aegypti mosquitoes were relatively refractory to an USUV infection, exhibiting low infection rates and lacking virus in their saliva. Conclusions Consistent with the high prevalences and abundances of Cx. pipiens biotype molestus and Cx. torrentium in Central and Northern Europe, these two species have most likely played a historic role in the spread, maintenance, and introduction of USUV into Germany. Identification of the key USUV vectors enables the establishment and implementation of rigorous entomological surveillance programs and the development of effective, evidence-based vector control interventions. Graphical Abstract

Usutu virus (USUV) is a mosquito-borne flavivirus that is widely distributed in southern and central Europe. The zoonotic virus circulates primarily between birds and mosquitoes, can, however, in rare cases infect other mammals including humans. In the past, USUV has been repeatedly associated with mass mortalities in birds, primarily blackbirds and owls. Birds commonly succumb either due to the peracute nature of the infection or due to severe encephalitis. In Germany, USUV has spread rapidly since its first detection in 2010 in mosquitoes under the presence of susceptible host and vector species. Nonetheless, there is to date limited access to whole genome sequences resulting in the absence of in-depth phylogenetic and phylodynamic analyses. In this study, 118 wild and captive birds were sequenced using a nanopore sequencing platform with prior target enrichment via amplicons. Due to the high abundancy of Europe 3 and Africa 3 in Germany an ample quantity of associated whole genome sequences was generated and the most recent common ancestor could be determined for each lineage. The corresponding clock phylogeny revealed an introduction of USUV Europe 3 and Africa 3 into Germany three years prior to their first isolation in the avifauna in 2011 and 2014, respectively. Based on the clustering and temporal history of the lineages, evidence exists for the genetic evolution of USUV within Germany as well as new introductions thereof into the country.

West Nile virus (WNV) is a widespread zoonotic arbovirus and a threat to public health in Germany since its first emergence in 2018. It has become of particular relevance in Germany in 2019 due to its rapid geographical spread and the detection of the first human clinical cases. The susceptibility of indigenous Culex pipiens (biotypes pipiens and molestus) for a German WNV lineage 2 strain was experimentally compared to that of Serbian Cx. pipiens biotype molestus and invasive German Aedes albopictus. All tested populations proved to be competent laboratory vectors of WNV. Culex pipiens biotype pipiens displayed the highest transmission efficiencies (40.0%–52.9%) at 25 °C. This biotype was also able to transmit WNV at 18 °C (transmission efficiencies of 4.4%–8.3%), proving that temperate climates in Central and Northern Europe may support WNV circulation. Furthermore, due to their feeding behaviors, Cx. pipiens biotype molestus and Ae. albopictus can act as “bridge vectors”, leading to human WNV infections.

The mosquito-borne flaviviruses West Nile virus (WNV) and Usutu virus (USUV) pose a significant threat to the health of humans and animals. Both viruses co-circulate in numerous European countries including Germany. Due to their overlapping host and vector ranges, there is a high risk of co-infections. However, it is largely unknown if WNV and USUV interact and how this might influence their epidemiology. Therefore, in-vitro infection experiments in mammalian (Vero B4), goose (GN-R) and mosquito cell lines (C6/36, CT) were performed to investigate potential effects of co-infections in vectors and vertebrate hosts. The growth kinetics of German and other European WNV and USUV strains were determined and compared. Subsequently, simultaneous co-infections were performed with selected WNV and USUV strains. The results show that the growth of USUV was suppressed by WNV in all cell lines. This effect was independent of the virus lineage but depended on the set WNV titre. The replication of WNV also decreased in co-infection scenarios on vertebrate cells. Overall, co-infections might lead to a decreased growth of USUV in mosquitoes and of both viruses in vertebrate hosts. These interactions can strongly affect the epidemiology of USUV and WNV in areas where they co-circulate.

Usutu virus (USUV) and West Nile virus (WNV) are known to cause diseases and mortalities in bird populations. Since 2010/2011, USUV has circulated in Germany and spread nationwide, while WNV was only introduced into East Germany in 2018. The zoological garden investigated is located in Northern Germany, where USUV infections in wild birds have been detected for several years. In this longitudinal study conducted over a four-year period, zoo birds were sampled biannually and screened for molecular and serological evidence of USUV and WNV. USUV genomes were detected in eight of the sampled birds and whole-genome sequences revealed the circulation of USUV lineages Europe 3 and Africa 3. Of the eight birds infected with USUV during the study period, four died after the infection, while four survived without displaying clinical signs. Furthermore, in a few of the birds, a USUV (re-)infection was confirmed on a serological level with three birds producing USUV-neutralizing antibodies (nAbs) over a period of four years. Nonetheless, in two birds sampled throughout this longitudinal study, neither a USUV nor a WNV infection was evident. In 2022, WNV nAbs were detected for the first time in a juvenile zoo bird, indicating the introduction of the virus into this region.