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12 pages, 826 KiB

Open AccessArticle

Severe Neurologic Disease in a Horse Caused by Tick-Borne Encephalitis Virus, Austria, 2021

by Phebe de Heus, Zoltán Bagó, Pia Weidinger, Dilara Lale, Dagmar S. Trachsel, Sandra Revilla-Fernández, Kaspar Matiasek and Norbert Nowotny

Viruses 2023, 15(10), 2022; https://doi.org/10.3390/v15102022 - 29 Sep 2023

Cited by 3 | Viewed by 2329

Abstract

As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this [...] Read more.

As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this study, ELISA and neutralization tests were applied to serum samples. Brain tissue samples were investigated for the presence of nucleic acids of TBEV, Equid alphaherpesvirus 1, Borna disease virus 1, West Nile and Usutu viruses, rustrela virus, as well as Eastern, Western, and Venezuelan equine encephalitis viruses with RT-qPCR, RT-PCR, and qPCR, respectively. TBEV-specific amplification products were subjected to Sanger sequencing. In addition, a direct fluorescent antibody test for rabies was performed. Clinical and patho-histological findings are reported. Using specific RT-qPCR and RT-PCR assays, TBEV nucleic acids were demonstrated in brain tissue samples. Sequencing revealed the Western (formerly Central) European subtype of TBEV as the etiological agent. A high titer of TBEV-specific neutralizing antibodies was found in the serum. RNAscope in situ hybridization revealed TBEV RNA confined to neuronal cell bodies and processes. No other pathogens or nucleic acids thereof could be detected. Diagnostic procedures need to be carried out early after the onset of neurological signs to allow for a final etiological diagnosis of acute TBEV infections in horses. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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10 pages, 2306 KiB

Open AccessArticle

Rustrela Virus-Associated Encephalomyelitis (‘Staggering Disease’) in Cats from Eastern Austria, 1994–2016

by Viktoria Weiss, Pia Weidinger, Julia Matt, Christiane Weissenbacher-Lang, Norbert Nowotny and Herbert Weissenböck

Viruses 2023, 15(8), 1621; https://doi.org/10.3390/v15081621 - 25 Jul 2023

Cited by 3 | Viewed by 1564

Abstract

Clinical cases of ‘staggering disease’, a nonsuppurative encephalomyelitis associated with gait abnormalities in cats, have been documented for decades in Sweden. In Austria, an increased incidence was observed in the 1990s. Only recently, rustrela virus (RusV) was identified as the causative agent of [...] Read more.

Clinical cases of ‘staggering disease’, a nonsuppurative encephalomyelitis associated with gait abnormalities in cats, have been documented for decades in Sweden. In Austria, an increased incidence was observed in the 1990s. Only recently, rustrela virus (RusV) was identified as the causative agent of this clinicopathologic disease entity. In this retrospective study, we analyzed a total of 23 brain and spinal cord samples from Austrian cats with the pathohistological diagnosis of nonsuppurative encephalomyelitis and clinical signs consistent with staggering disease from 1994 to 2016 using reverse transcription real-time polymerase chain reaction (RT-qPCR) and in situ hybridization. We were able to detect RusV nucleic acids in seven of the examined samples. Borna disease virus 1 (BoDV-1) could be excluded in all cases via immunohistochemistry and RT-qPCR. This study confirms that RusV has been a relevant etiological agent of nonsuppurative encephalomyelitis of cats in a geographically and temporally limited disease cluster in Austria, mainly in the 1990s. The geographic distribution of the positive samples in this study is consistent with earlier reports on ‘staggering disease’ in Austria. Further studies are necessary to confirm the reservoir host of ‘staggering disease’ in Austria, as well as investigations on the disappearance of this disease and its possible zoonotic potential. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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12 pages, 439 KiB

Open AccessArticle

MERS-CoV Found in Hyalomma dromedarii Ticks Attached to Dromedary Camels at a Livestock Market, United Arab Emirates, 2019

by Pia Weidinger, Jolanta Kolodziejek, Tom Loney, Dafalla O. Kannan, Babiker Mohammed Osman, Tamer Khafaga, Brigitte Howarth, Moayyed Sher Shah, Hessa Mazrooei, Nadine Wolf, Noushad Karuvantevida, Ahmad Abou Tayoun, Alawi Alsheikh-Ali, Jeremy V. Camp and Norbert Nowotny

Viruses 2023, 15(6), 1288; https://doi.org/10.3390/v15061288 - 30 May 2023

Cited by 2 | Viewed by 2604

Abstract

The main mode of transmission of Middle East respiratory syndrome-related coronavirus (MERS-CoV) between dromedaries is likely via the respiratory route. However, there must be other modes to explain how the infection is brought to MERS-CoV-negative closed herds, such as transmission by ticks. Here, [...] Read more.

The main mode of transmission of Middle East respiratory syndrome-related coronavirus (MERS-CoV) between dromedaries is likely via the respiratory route. However, there must be other modes to explain how the infection is brought to MERS-CoV-negative closed herds, such as transmission by ticks. Here, we present a study performed at three different locations in the United Arab Emirates (UAE) involving 215 dromedary camels (Camelus dromedarius) and the ticks attached to them. We tested the camels and ticks via RT-(q)PCR for the presence of MERS-CoV nucleic acids, as well as flaviviruses that may be present in the region (e.g., Alkhumra hemorrhagic fever virus). Camel sera were additionally analyzed for evidence of previous exposure to MERS-CoV. In total, 8 out of 242 tick pools were positive for MERS-CoV RNA (3.3%; C_t 34.6–38.3), 7 of which contained Hyalomma dromedarii ticks, and one contained a Hyalomma sp. tick (species not identified). All of the virus-positive ticks’ host camels were also positive for MERS-CoV RNA in their nasal swab samples. Short sequences established in the N gene region from two positive tick pools were identical to viral sequences from their hosts’ nasal swabs. In total, 59.3% of dromedaries at the livestock market had MERS-CoV RNA in their nasal swabs (C_t 17.7–39.5). While dromedaries at all locations were negative for MERS-CoV RNA in their serum samples, antibodies were detected in 95.2% and 98.7% of them (tested by ELISA and indirect immunofluorescence test, respectively). Given the probably transient and/or low level of MERS-CoV viremia in dromedaries and the rather high C_t values observed in the ticks, it seems unlikely that Hyalomma dromedarii is a competent vector for MERS-CoV; however, its role in mechanical or fomite transmission between camels should be investigated. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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9 pages, 573 KiB

Open AccessArticle

Efficacy of Sotrovimab (SOT), Molnupiravir (MOL), and Nirmatrelvir/Ritponavir (N/R) and Tolerability of Molnupiravir in Outpatients at High Risk for Severe COVID-19

by Victoria Kauer, David Totschnig, Ferdinand Waldenberger, Max Augustin, Mario Karolyi, Michelle Nägeli, Christoph Wenisch and Alexander Zoufaly

Viruses 2023, 15(5), 1181; https://doi.org/10.3390/v15051181 - 17 May 2023

Cited by 4 | Viewed by 1832

Abstract

Objective: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. Methods: We conducted a retrospective analysis on 2606 [...] Read more.

Objective: The main goal of this study was to assess the potential clinical impact of an outpatient administration of available antivirals including SOT, N/R, and MOL to COVID-19 patients at high risk for disease progression. Methods: We conducted a retrospective analysis on 2606 outpatient individuals with mild to moderate COVID-19 at risk for disease progression, hospitalization, or death. After receiving either SOT (420/2606), MOL (1788/2606), or N/R (398/2606), patients were followed-up with regarding primary (hospitalization rate) and secondary (treatment and side effects) outcomes by phone. Result: A total of 2606 patients were treated at the outpatient clinic (SOT: 420; N/R: 398; MOL: 1788). 3.2% of the SOT patients (1 ICU admission), 0.8% of the MOL patients (2 ICU admissions), and none of the N/R patients were hospitalized. 14.3% of the N/R patients reported strong to severe side effects, exceeding SOT (2.6%) and MOL (5%) patients. A reduction in COVID symptoms after the treatment was experienced by 43% of patients in both the SOT and MOL groups and by 67% of patients in the N/R group, respectively. Women had a higher chance of symptom improvement with MOL (OR 1.2, 95%CI 1.0–1.5). Conclusion: All antiviral treatment options effectively prevented hospitalization in high-risk COVID-19 patients and were well tolerated. Side effects were pronounced in patients with N/R. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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15 pages, 1390 KiB

Open AccessArticle

Potentially Zoonotic Viruses in Wild Rodents, United Arab Emirates, 2019—A Pilot Study

by Pia Weidinger, Jolanta Kolodziejek, Tamer Khafaga, Tom Loney, Brigitte Howarth, Moayyed Sher Shah, Ahmad Abou Tayoun, Alawi Alsheikh-Ali, Jeremy V. Camp and Norbert Nowotny

Viruses 2023, 15(3), 695; https://doi.org/10.3390/v15030695 - 7 Mar 2023

Cited by 3 | Viewed by 2701

Abstract

The majority of emerging viral infectious diseases in humans originate from wildlife reservoirs, such as rodents and bats. We investigated a possible reservoir, namely wild gerbils and mice trapped in a desert reserve within the emirate of Dubai, United Arab Emirates (UAE). In [...] Read more.

The majority of emerging viral infectious diseases in humans originate from wildlife reservoirs, such as rodents and bats. We investigated a possible reservoir, namely wild gerbils and mice trapped in a desert reserve within the emirate of Dubai, United Arab Emirates (UAE). In total, 52 gerbils and 1 jird (Gerbillinae), 10 house mice (Mus musculus), and 1 Arabian spiny mouse (Acomys dimidiatus) were sampled. Oro-pharyngeal swabs, fecal samples, attached ticks, and organ samples (where available) were screened by (RT-q)PCR for the following viruses: Middle East respiratory syndrome-related coronavirus, Crimean-Congo hemorrhagic fever orthonairovirus, Alkhumra hemorrhagic fever virus, hantaviruses, Lymphocytic choriomeningitis mammarenavirus, Rustrela virus, poxviruses, flaviviruses, and herpesviruses. All of the samples were negative for all investigated viruses, except for herpesviruses: 19 gerbils (35.8%) and seven house mice (70.0%) were positive. The resulting sequences were only partly identical to sequences in GenBank. Phylogenetic analysis revealed three novel betaherpesviruses and four novel gammaherpesviruses. Interestingly, species identification of the positive gerbils resulted in eight individuals clustering in a separate clade, most closely related to Dipodillus campestris, the North African gerbil, indicating either the expansion of the geographic range of this species, or the existence of a closely related, yet undiscovered species in the UAE. In conclusion, we could not find evidence of persistence or shedding of potentially zoonotic viruses in the investigated rodent cohorts of limited sample size. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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13 pages, 1977 KiB

Open AccessArticle

A Conserved Stem-Loop Structure within ORF5 Is a Frequent Recombination Hotspot for Porcine Reproductive and Respiratory Syndrome Virus 1 (PRRSV-1) with a Particular Modified Live Virus (MLV) Strain

by Marlene Mötz, Julia Stadler, Heinrich Kreutzmann, Andrea Ladinig, Benjamin Lamp, Angelika Auer, Christiane Riedel and Till Rümenapf

Viruses 2023, 15(1), 258; https://doi.org/10.3390/v15010258 - 16 Jan 2023

Cited by 5 | Viewed by 2756

Abstract

The emergence of recombinant PRRSV strains has been observed for more than a decade. These recombinant viruses are characterized by a genome that contains genetic material from at least two different parental strains. Due to the advanced sequencing techniques and a growing number [...] Read more.

The emergence of recombinant PRRSV strains has been observed for more than a decade. These recombinant viruses are characterized by a genome that contains genetic material from at least two different parental strains. Due to the advanced sequencing techniques and a growing number of data bank entries, the role of PRRSV recombinants has become increasingly important since they are sometimes associated with clinical outbreaks. Chimeric viruses observed more recently are products of PRRSV wild-type and vaccine strains. Here, we report on three PRRSV-1 isolates from geographically distant farms with differing clinical manifestations. A sequencing and recombination analysis revealed that these strains are crossovers between different wild-type strains and the same modified live virus vaccine strain. Interestingly, the recombination breakpoint of all analyzed isolates appears at the beginning of open reading frame 5 (ORF5). RNA structure predictions indicate a conserved stem loop in close proximity to the recombination hotspot, which is a plausible cause of a polymerase template switch during RNA replication. Further research into the mechanisms of the stem loop is needed to help understand the PRRSV recombination process and the role of MLVs as parental strains. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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11 pages, 618 KiB

Open AccessArticle

Only Subclinical Alterations in the Haemostatic System of People with Diabetes after COVID-19 Vaccination

by Margret Paar, Faisal Aziz, Caren Sourij, Norbert J. Tripolt, Harald Kojzar, Alexander Müller, Peter Pferschy, Anna Obermayer, Tamara Banfic, Bruno Di Geronimo Quintero, Nandu Goswami, Axel Schlagenhauf, Martin Köstenberger, Thomas Bärnthaler, Thomas Wagner, Andelko Hrzenjak, Willibald Wonisch, Gilbert Reibnegger, Reinhard B. Raggam, Harald Sourij and Gerhard Cvirn Show full author list Hide full author list

Viruses 2023, 15(1), 10; https://doi.org/10.3390/v15010010 - 20 Dec 2022

Cited by 1 | Viewed by 1881

Abstract

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient [...] Read more.

People with diabetes have an increased risk of experiencing adverse COVID-19 outcomes. COVID-19 vaccination is, therefore, highly recommended. However, people with diabetes have an inherently elevated risk of thrombotic events and the impact of the vaccination on the coagulation system in this patient population remains to be elucidated. The aim of this study was to investigate the impact of COVID-19 vaccination on the haemostatic system in people with type 1 or type 2 diabetes. We evaluated the effects of COVID-19 vaccination (BioNTech Pfizer, Moderna, AstraZeneca) on standard coagulation parameters, whole blood coagulation (Thrombelastometry), platelet function (impedance aggregation), and thrombin generation (calibrated automated thrombography) in people with type 1 diabetes mellitus (n = 41) and type 2 diabetes mellitus (n = 37). Blood sampling points were prior to vaccination and two weeks after the respective vaccination. Thrombelastometry measurements indicated moderately increased clot formation post-vaccination in people with type 1, as well as with type 2, diabetes: “Clot formation times” were significantly shorter, and both “maximum clot firmness” and “alpha angles” were significantly higher, as compared to the respective pre-vaccination values. Therefore, TEM parameters were not altered after vaccination in patients receiving ASA. Moreover, platelet aggregation was enhanced in people with type 1 diabetes, and plasma levels of D-Dimer were increased in people with type 2 diabetes, following COVID-19 vaccination. All other standard coagulation parameters, as well as thrombin generation, were not affected by the vaccination. The coagulation responses of people with diabetes to COVID-19 vaccination were only subclinical and comparable to those observed in healthy individuals. Our findings suggest that people with diabetes do not face an increased activation of the coagulation post-vaccination. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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12 pages, 564 KiB

Open AccessArticle

The Role of Bacterial and Fungal Superinfection in Critical COVID-19

by Tamara Seitz, Johannes Holbik, Alexander Grieb, Mario Karolyi, Julian Hind, Georg Gibas, Stephanie Neuhold, Alexander Zoufaly and Christoph Wenisch

Viruses 2022, 14(12), 2785; https://doi.org/10.3390/v14122785 - 14 Dec 2022

Cited by 6 | Viewed by 1702

Abstract

Background: The range of reported rates of bacterial and fungal superinfections in patients with a severe course of COVID-19 is wide, suggesting a lack of standardised reporting. Methods: The rates of bacterial and fungal superinfection were assessed using predefined criteria to differentiate between [...] Read more.

Background: The range of reported rates of bacterial and fungal superinfections in patients with a severe course of COVID-19 is wide, suggesting a lack of standardised reporting. Methods: The rates of bacterial and fungal superinfection were assessed using predefined criteria to differentiate between infection and contamination. Results: Overall, 117 patients admitted to the Intensive Care Unit due to severe COVID-19 were included. Overall, 55% of patients developed a superinfection and 13.6% developed a fungal superinfection (5.9% candidemia and 7.7% CAPA). The rate of ventilator-associated pneumonia was 65.2%. If superinfection was detected, the length of hospital stay was significantly longer and the mortality was especially increased if candidemia was detected. An increased risk of superinfection was observed in patients with pre-existing diabetes mellitus or chronic heart failure. The presence of immunomodulating therapy did not seem to have an impact on the frequency of superinfections. Conclusion: Increased awareness of high superinfection rates, fungal infections in particular, in patients suffering from severe COVID-19 is necessary. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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13 pages, 4070 KiB

Open AccessArticle

Bovine Papillomavirus Type 1 or 2 Virion-Infected Primary Fibroblasts Constitute a Near-Natural Equine Sarcoid Model

by Edmund K. Hainisch, Christoph Jindra, Paul Reicher, Lea Miglinci, Daniela M. Brodesser and Sabine Brandt

Viruses 2022, 14(12), 2658; https://doi.org/10.3390/v14122658 - 28 Nov 2022

Cited by 3 | Viewed by 1896

Abstract

Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these [...] Read more.

Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 10⁶-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four passages. Infected cells displayed typical features of equine sarcoid cells, including hyperproliferation, and loss of contact inhibition. Neither multiple passaging nor storage negatively affected cell hyperproliferation, viral DNA replication, and gene transcription, suggestive for infection-mediated cell immortalization. Intriguingly, extracellular vesicles released by BPV1-infected fibroblasts contained viral DNA that was most abundant in the fractions enriched for apoptotic bodies and exosomes. This viral DNA is likely taken up by non-infected fibroblasts. We conclude that equine primary fibroblasts stably infected with BPV1 and BPV2 virions constitute a valuable near-natural model for the study of yet unexplored mechanisms underlying the pathobiology of BPV1/2-induced sarcoids. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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12 pages, 645 KiB

Open AccessArticle

High Prevalence of Undocumented SARS-CoV-2 Infections in the Pediatric Population of the Tyrolean District of Schwaz

by Teresa Harthaller, Wegene Borena, David Bante, Helena Schäfer, Oliver Strallhofer, Thomas Zöggeler, Eva Hochmuth, Luiza Hoch, Annika Rössler, Dorothee von Laer, Janine Kimpel and Barbara Falkensammer

Viruses 2022, 14(10), 2294; https://doi.org/10.3390/v14102294 - 19 Oct 2022

Cited by 2 | Viewed by 1804

Abstract

Complementing the adult seroprevalence data collected at the time of the rapid SARS-CoV-2 mass vaccination in the district of Schwaz in 2021, we set out to establish the seroprevalence of SARS-CoV-2 among the pediatric population of the district. A total of 369 children, [...] Read more.

Complementing the adult seroprevalence data collected at the time of the rapid SARS-CoV-2 mass vaccination in the district of Schwaz in 2021, we set out to establish the seroprevalence of SARS-CoV-2 among the pediatric population of the district. A total of 369 children, mean age 9.9 (SD 3.4), participated in the study, answering a structured questionnaire on the history of SARS-CoV-2 infection, household contacts, symptoms and history of vaccination. We determined binding and neutralizing antibody levels using plasma samples provided. We estimated the overall prevalence of SARS-CoV-2 infection in the general pediatric population at the time of the study using the census data from Statistik Austria and daily reports of officially confirmed cases. Excluding study participants who reported a history of PCR-confirmed infection, the age-standardized seroprevalence of previously unknown SARS-CoV-2 infection among the general pediatric population of the district was 27% (95% CI: 26.1–27.8). Adding this to the officially documented cases, the true overall prevalence was 32.8% (95% CI: 31.9–33.6) in contrast to the officially documented 8.0% (95% CI: 7.5–8.5) by June 2021. This translated into a proportion of 75.7% (95% CI: 74.4–77.0) of cases being officially undocumented, suggesting a high extent of silent SARS-CoV-2 infections in the pediatric population and possibly silent transmission. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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11 pages, 1508 KiB

Open AccessArticle

SARS-CoV-2 Pre-Exposure Prophylaxis with Sotrovimab and Tixagevimab/Cilgavimab in Immunocompromised Patients—A Single-Center Experience

by David Totschnig, Max Augustin, Iulia Niculescu, Hermann Laferl, Sonja Jansen-Skoupy, Clara Lehmann, Christoph Wenisch and Alexander Zoufaly

Viruses 2022, 14(10), 2278; https://doi.org/10.3390/v14102278 - 17 Oct 2022

Cited by 12 | Viewed by 3110

Abstract

Immunocompromised patients experience reduced vaccine effectiveness and are at higher risk for coronavirus disease 19 (COVID-19) death. Pre-exposure prophylaxis (PrEP) aims to protect these patients. So far, only tixagevimab/cilgavimab is authorized for use as PrEP. This paper aims to provide real-world data on [...] Read more.

Immunocompromised patients experience reduced vaccine effectiveness and are at higher risk for coronavirus disease 19 (COVID-19) death. Pre-exposure prophylaxis (PrEP) aims to protect these patients. So far, only tixagevimab/cilgavimab is authorized for use as PrEP. This paper aims to provide real-world data on the use of tixagevimab/cilgavimab and sotrovimab as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) PrEP in immunocompromised patients, comparing the evolution of antibody levels and reporting the incidence of breakthrough infections. A retrospective, single-center analysis was conducted including 132 immunocompromised patients with inadequate vaccine response, who received COVID-PrEP at our clinic between January and June 2022. Initially, 95 patients received sotrovimab while 37 patients received tixagevimab/cilgavimab. Antibody levels after first PrEP with sotrovimab remain high for several months after infusion (median 10,058 and 7235 BAU/mL after 1 and 3 months, respectively), with higher titers than after tixagevimab/cilgavimab injection even 3 months later (7235 vs. 1647 BAU/mL, p = 0.0007). Overall, breakthrough infections were rare (13/132, 10%) when compared to overall infection rates during this period (over 30% of the Austrian population), with mild disease course and rapid viral clearance (median 10 days). Sotrovimab may be an additional option for SARS-CoV-2 PrEP. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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16 pages, 1505 KiB

Open AccessArticle

Human Cytomegalovirus Induces Vitamin-D Resistance In Vitro by Dysregulating the Transcriptional Repressor Snail

by Carmen Stecher, Katharina Philomena Maurer, Marie-Theres Kastner and Christoph Steininger

Viruses 2022, 14(9), 2004; https://doi.org/10.3390/v14092004 - 10 Sep 2022

Cited by 2 | Viewed by 3166

Abstract

Vitamin-D supplementation is considered to play a beneficial role against multiple viruses due to its immune-regulating and direct antimicrobial effects. In contrast, the human cytomegalovirus (HCMV) has shown to be resistant to treatment with vitamin D in vitro by downregulation of the vitamin-D [...] Read more.

Vitamin-D supplementation is considered to play a beneficial role against multiple viruses due to its immune-regulating and direct antimicrobial effects. In contrast, the human cytomegalovirus (HCMV) has shown to be resistant to treatment with vitamin D in vitro by downregulation of the vitamin-D receptor. In this study, we aimed to elucidate the mechanism and possible biological consequences of vitamin-D resistance during HCMV infection. Mechanistically, HCMV induced vitamin-D resistance by downregulating the vitamin-D receptor (VDR) within hours of lytic infection. We found that the VDR was inhibited at the promoter level, and treatment with histone deacetylase inhibitors could restore VDR expression. VDR downregulation highly correlated with the upregulation of the transcriptional repressor Snail1, a mechanism likely contributing to the epigenetic inactivation of the VDR promoter, since siRNA-mediated knockdown of Snail partly restored levels of VDR expression. Finally, we found that direct addition of the vitamin-D-inducible antimicrobial peptide LL-37 strongly and significantly reduced viral titers in infected fibroblasts, highlighting VDR biological relevance and the potential of vitamin-D-inducible peptides for the antiviral treatment of vitamin-D deficient patients. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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17 pages, 1758 KiB

Open AccessArticle

Identification of MHC-I-Presented Porcine Respiratory and Reproductive Syndrome Virus (PRRSV) Peptides Reveals Immunogenic Epitopes within Several Non-Structural Proteins Recognized by CD8⁺ T Cells

by Marlene Mötz, Melissa R. Stas, Sabine E. Hammer, Tereza Duckova, Frederic Fontaine, Alexandra Kiesler, Kerstin Seitz, Andrea Ladinig, André C. Müller, Christiane Riedel, Armin Saalmüller and Till Rümenapf

Viruses 2022, 14(9), 1891; https://doi.org/10.3390/v14091891 - 26 Aug 2022

Cited by 6 | Viewed by 2881

Abstract

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most relevant porcine pathogens worldwide. Active control of the disease relies on modified live virus vaccines (MLVs), as most inactivated vaccines provide very limited protection. Neutralizing antibodies occur late in infection; therefore, [...] Read more.

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most relevant porcine pathogens worldwide. Active control of the disease relies on modified live virus vaccines (MLVs), as most inactivated vaccines provide very limited protection. Neutralizing antibodies occur late in infection; therefore, CD8⁺ T cells are considered important correlates of protection and are a frequent focus of investigation. Our aim was to identify viral peptides naturally bound by the class I major histocompatibility complex (MHC-I) and to confirm their ability to stimulate CD8⁺ T cells. For this purpose, we immunoprecipitated MHC-I/peptide complexes of PRRSV (strain AUT15-33) -infected cells (SLA-I Lr-Hp 35.0/24 mod) to isolate the viral epitopes and analyzed them with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). Furthermore, we employed these identified peptides to stimulate peripheral blood mononuclear cells (PBMCs) of previously PRRSV-infected pigs and measured the PRRSV-specific CD8⁺ T-cell response with an intracellular cytokine staining (ICS). Our data revealed that PRRSV non-structural proteins (NSPs), encoded in open reading frame 1a and 1b (ORF1), present the major source of MHC-I-presented peptides. Additionally, we show that our identified epitopes are able to trigger IFNγ responses in vitro. These findings are a basis for understanding the proteasomal degradation of PRRSV proteins, the cellular ability to display them via MHC-I, and their potential to restimulate CD8⁺ T cells. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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12 pages, 899 KiB

Open AccessArticle

Seroprevalence of Anti-SARS-CoV-2 IgG Antibodies in Tyrol, Austria: Updated Analysis Involving 22,607 Blood Donors Covering the Period October 2021 to April 2022

by Lisa Seekircher, Anita Siller, Manfred Astl, Lena Tschiderer, Gregor A. Wachter, Bernhard Pfeifer, Andreas Huber, Manfred Gaber, Harald Schennach and Peter Willeit

Viruses 2022, 14(9), 1877; https://doi.org/10.3390/v14091877 - 25 Aug 2022

Cited by 7 | Viewed by 2150

Abstract

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 [...] Read more.

Because a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies. We quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%). Median age of participants was 45.3 years (IQR: 30.9–55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8–86.0%) to 95.8% (94.9–96.4%), and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271–296) to 1437 (1360–1518) BAU/mL. The percentages of participants in categories with undetectable levels and detectable levels at <500, 500–<1000, 1000–<2000, 2000–<3000, and ≥3000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2–19.9; p-value < 0.001). In conclusion, anti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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12 pages, 2533 KiB

Open AccessArticle

Six-Month Follow-Up of Immune Responses after a Rapid Mass Vaccination against SARS-CoV-2 with BNT162b2 in the District of Schwaz/Austria

by Zoltán Bánki, Lisa Seekircher, Barbara Falkensammer, David Bante, Helena Schäfer, Teresa Harthaller, Janine Kimpel, Peter Willeit, Dorothee von Laer and Wegene Borena

Viruses 2022, 14(8), 1642; https://doi.org/10.3390/v14081642 - 27 Jul 2022

Cited by 4 | Viewed by 1872

Abstract

In response to a large outbreak of the SARS-CoV-2 Beta (B.1.351) variant in the district Schwaz, Austria, a rapid mass vaccination campaign with BNT162b2 was carried out in spring 2021, immunizing more than 70% of the adult population within one week. Subsequent analysis [...] Read more.

In response to a large outbreak of the SARS-CoV-2 Beta (B.1.351) variant in the district Schwaz, Austria, a rapid mass vaccination campaign with BNT162b2 was carried out in spring 2021, immunizing more than 70% of the adult population within one week. Subsequent analysis revealed that the mass vaccination was associated with a significant reduction in new SARS-CoV-2 infections compared to control districts. Here, we aimed to evaluate both SARS-CoV-2-specific T- and B-cell responses at 35 ± 8 and 215 ± 7 days after the second dose in 600 study subjects who participated at both time points. Overall, a robust antibody and T-cell response was measured at day 35, which waned over time. Nevertheless, all persons preserved seropositivity and T cell response could still be detected in about half of the participants at day 215. Further, antibody response correlated negatively with age; however, in persons who experienced SARS-CoV-2 infection prior to study enrolment, the serum levels of both S- and N-specific antibodies surprisingly increased with age. In contrast, there was no correlation of T cell response with age. We could not detect any sex-related difference in the immune responses. SARS-CoV-2 infections prior to study enrolment or incident infections before day 215 resulted in higher antibody levels and T cell responses at day 215 compared to study participants with no history of infection. Collectively, our data support that vaccination with BNT162b2 against COVID-19 provides a durable immune response and emphasize the usefulness of vaccination even after a natural infection. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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12 pages, 338 KiB

Open AccessArticle

Monitoring Urban Zoonotic Virus Activity: Are City Rats a Promising Surveillance Tool for Emerging Viruses?

by Jeremy V. Camp, Amélie Desvars-Larrive, Norbert Nowotny and Chris Walzer

Viruses 2022, 14(7), 1516; https://doi.org/10.3390/v14071516 - 11 Jul 2022

Cited by 5 | Viewed by 3049

Abstract

Urban environments represent unique ecosystems where dense human populations may come into contact with wildlife species, some of which are established or potential reservoirs for zoonotic pathogens that cause human diseases. Finding practical ways to monitor the presence and/or abundance of zoonotic pathogens [...] Read more.

Urban environments represent unique ecosystems where dense human populations may come into contact with wildlife species, some of which are established or potential reservoirs for zoonotic pathogens that cause human diseases. Finding practical ways to monitor the presence and/or abundance of zoonotic pathogens is important to estimate the risk of spillover to humans in cities. As brown rats (Rattus norvegicus) are ubiquitous in urban habitats, and are hosts of several zoonotic viruses, we conducted longitudinal sampling of brown rats in Vienna, Austria, a large population center in Central Europe. We investigated rat tissues for the presence of several zoonotic viruses, including flaviviruses, hantaviruses, coronaviruses, poxviruses, hepatitis E virus, encephalomyocarditis virus, and influenza A virus. Although we found no evidence of active infections (all were negative for viral nucleic acids) among 96 rats captured between 2016 and 2018, our study supports the findings of others, suggesting that monitoring urban rats may be an efficient way to estimate the activity of zoonotic viruses in urban environments. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

13 pages, 2737 KiB

Open AccessArticle

Biomarkers Predictive for In-Hospital Mortality in Patients with Diabetes Mellitus and Prediabetes Hospitalized for COVID-19 in Austria: An Analysis of COVID-19 in Diabetes Registry

by Faisal Aziz, Hannah Stöcher, Alexander Bräuer, Christian Ciardi, Martin Clodi, Peter Fasching, Mario Karolyi, Alexandra Kautzky-Willer, Carmen Klammer, Oliver Malle, Felix Aberer, Erich Pawelka, Slobodan Peric, Claudia Ress, Caren Sourij, Lars Stechemesser, Harald Stingl, Thomas Stulnig, Norbert Tripolt, Michael Wagner, Peter Wolf, Andreas Zitterl, Othmar Moser, Christian Schelkshorn, Susanne Kaser, Harald Sourij and for the COVID-19 in Diabetes in Austria Show full author list Hide full author list

Viruses 2022, 14(6), 1285; https://doi.org/10.3390/v14061285 - 13 Jun 2022

Cited by 3 | Viewed by 2600

Abstract

Background: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. Methods: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or [...] Read more.

Background: This study assessed the predictive performance of inflammatory, hepatic, coagulation, and cardiac biomarkers in patients with prediabetes and diabetes mellitus hospitalized for COVID-19 in Austria. Methods: This was an analysis of a multicenter cohort study of 747 patients with diabetes mellitus or prediabetes hospitalized for COVID-19 in 11 hospitals in Austria. The primary outcome of this study was in-hospital mortality. The predictor variables included demographic characteristics, clinical parameters, comorbidities, use of medication, disease severity, and laboratory measurements of biomarkers. The association between biomarkers and in-hospital mortality was assessed using simple and multiple logistic regression analyses. The predictive performance of biomarkers was assessed using discrimination and calibration. Results: In our analysis, 70.8% had type 2 diabetes mellitus, 5.8% had type 1 diabetes mellitus, 14.9% had prediabetes, and 8.6% had other types of diabetes mellitus. The mean age was 70.3 ± 13.3 years, and 69.3% of patients were men. A total of 19.0% of patients died in the hospital. In multiple logistic regression analysis, LDH, CRP, IL-6, PCT, AST-ALT ratio, NT-proBNP, and Troponin T were significantly associated with in-hospital mortality. The discrimination of NT-proBNP was 74%, and that of Troponin T was 81%. The calibration of NT-proBNP was adequate (p = 0.302), while it was inadequate for Troponin T (p = 0.010). Conclusion: Troponin T showed excellent predictive performance, while NT-proBNP showed good predictive performance for assessing in-hospital mortality in patients with diabetes mellitus hospitalized with COVID-19. Therefore, these cardiac biomarkers may be used for prognostication of COVID-19 patients. Full article

(This article belongs to the Special Issue State-of-the-Art Virology Research in Austria)

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