Viruses

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22 pages, 2157 KiB

Open AccessArticle

Tropism of Puumala orthohantavirus and Endoparasite Coinfection in the Bank Vole Reservoir

by Elfi K. Schlohsarczyk, Stephan Drewes, Paweł Koteja, Susanne Röhrs, Rainer G. Ulrich, Jens P. Teifke and Christiane Herden

Viruses 2023, 15(3), 612; https://doi.org/10.3390/v15030612 - 23 Feb 2023

Cited by 2 | Viewed by 1624

Abstract

In Europe, most cases of human hantavirus disease are caused by Puumala orthohantavirus (PUUV) transmitted by bank voles (Clethrionomys glareolus, syn. Myodes glareolus), in which PUUV causes inconspicuous infection. Little is known about tropism and endoparasite coinfections in PUUV-infected reservoir and [...] Read more.

In Europe, most cases of human hantavirus disease are caused by Puumala orthohantavirus (PUUV) transmitted by bank voles (Clethrionomys glareolus, syn. Myodes glareolus), in which PUUV causes inconspicuous infection. Little is known about tropism and endoparasite coinfections in PUUV-infected reservoir and spillover-infected rodents. Here, we characterized PUUV tropism, pathological changes and endoparasite coinfections. The voles and some non-reservoir rodents were examined histologically, immunohistochemically, by in situ hybridization, indirect IgG enzyme-linked immunosorbent assay and reverse transcription-polymerase chain reaction. PUUV RNA and anti-PUUV antibodies were detected simultaneously in a large proportion of the bank voles, indicating persistent infection. Although PUUV RNA was not detected in non-reservoir rodents, the detection of PUUV-reactive antibodies suggests virus contact. No specific gross and histological findings were detected in the infected bank voles. A broad organ tropism of PUUV was observed: kidney and stomach were most frequently infected. Remarkably, PUUV was detected in cells lacking the typical secretory capacity, which may contribute to the maintenance of virus persistence. PUUV-infected wild bank voles were found to be frequently coinfected with Hepatozoon spp. and Sarcocystis (Frenkelia) spp., possibly causing immune modulation that may influence susceptibility to PUUV infection or vice versa. The results are a prerequisite for a deeper understanding of virus–host interactions in natural hantavirus reservoirs. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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18 pages, 1679 KiB

Open AccessArticle

Characterization of a Panel of Cross-Reactive Hantavirus Nucleocapsid Protein-Specific Monoclonal Antibodies

by Aliona Avižinienė, Indrė Kučinskaitė-Kodzė, Rasa Petraitytė-Burneikienė, Aurelija Žvirblienė, Marc L. Mertens, Sabrina Schmidt, Mathias Schlegel, Erik Lattwein, Bernd Koellner and Rainer G. Ulrich

Viruses 2023, 15(2), 532; https://doi.org/10.3390/v15020532 - 14 Feb 2023

Cited by 3 | Viewed by 1658

Abstract

Hantaviruses are emerging pathogens with a worldwide distribution that can cause life-threatening diseases in humans. Monoclonal antibodies (MAbs) against hantavirus nucleocapsid (N) proteins are important tools in virus diagnostics, epidemiological studies and basic research studies on virus replication and pathogenesis. Here, we extend [...] Read more.

Hantaviruses are emerging pathogens with a worldwide distribution that can cause life-threatening diseases in humans. Monoclonal antibodies (MAbs) against hantavirus nucleocapsid (N) proteins are important tools in virus diagnostics, epidemiological studies and basic research studies on virus replication and pathogenesis. Here, we extend the collection of previously generated MAbs raised against a segment of Puumala orthohantavirus (PUUV) N protein harbored on virus-like particles (VLPs) and MAbs against N proteins of Sin Nombre orthohantavirus/Andes orthohantavirus by generating nine novel MAbs against N proteins of Dobrava-Belgrade orthohantavirus (DOBV), Tula orthohantavirus (TULV), Thottapalayam thottimvirus (TPMV) and PUUV. In order to have a wide collection of well-described hantavirus-specific MAbs, the cross-reactivity of novel and previously generated MAbs was determined against N proteins of 15 rodent- and shrew-borne hantaviruses by different immunological methods. We found that all MAbs, excluding TPMV-specific MAbs, demonstrated different cross-reactivity patterns with N proteins of hantaviruses and recognized native viral antigens in infected mammalian cells. This well-characterized collection of cross-reactive hantavirus-specific MAbs has a potential application in various fields of hantavirus research, diagnostics and therapy. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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15 pages, 1667 KiB

Open AccessArticle

Pet Rats as the Likely Reservoir for Human Seoul Orthohantavirus Infection

by Elisa Heuser, Stephan Drewes, Jakob Trimpert, Dusan Kunec, Calvin Mehl, Marieke P. de Cock, Ankje de Vries, Christiane Klier, Martin Oskamp, Peter Tenhaken, Fatima Hashemi, Daniela Heinz, Mariana Nascimento, Marc Boelhauve, Rasa Petraityte-Burneikiene, Dina Raafat, Miriam Maas, Detlev H. Krüger, Andreas Latz, Jörg Hofmann, Gerald Heckel, Johannes Dreesman and Rainer G. Ulrich Show full author list Hide full author list

Viruses 2023, 15(2), 467; https://doi.org/10.3390/v15020467 - 07 Feb 2023

Cited by 5 | Viewed by 2477

Abstract

Seoul orthohantavirus (SEOV) is a rat-associated zoonotic pathogen with an almost worldwide distribution. In 2019, the first autochthonous human case of SEOV-induced hemorrhagic fever with renal syndrome was reported in Germany, and a pet rat was identified as the source of the zoonotic [...] Read more.

Seoul orthohantavirus (SEOV) is a rat-associated zoonotic pathogen with an almost worldwide distribution. In 2019, the first autochthonous human case of SEOV-induced hemorrhagic fever with renal syndrome was reported in Germany, and a pet rat was identified as the source of the zoonotic infection. To further investigate the SEOV reservoir, additional rats from the patient and another owner, all of which were purchased from the same vendor, were tested. SEOV RNA and anti-SEOV antibodies were found in both of the patient’s rats and in two of the three rats belonging to the other owner. The complete coding sequences of the small (S), medium (M), and large (L) segments obtained from one rat per owner exhibited a high sequence similarity to SEOV strains of breeder rat or human origin from the Netherlands, France, the USA, and Great Britain. Serological screening of 490 rats from breeding facilities and 563 wild rats from Germany (2007–2020) as well as 594 wild rats from the Netherlands (2013–2021) revealed 1 and 6 seropositive individuals, respectively. However, SEOV RNA was not detected in any of these animals. Increased surveillance of pet, breeder, and wild rats is needed to identify the origin of the SEOV strain in Europe and to develop measures to prevent transmission to the human population. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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13 pages, 1937 KiB

Open AccessArticle

Molecular Characterisation and Phylogeny of Tula Virus in Kazakhstan

by Nur Tukhanova, Anna Shin, Nurkeldi Turebekov, Talgat Nurmakhanov, Karlygash Abdiyeva, Alexandr Shevtsov, Toktasyn Yerubaev, Gulnara Tokmurziyeva, Almas Berdibekov, Vitaliy Sutyagin, Nurbek Maikanov, Andrei Zakharov, Ilmars Lezdinsh, Lyazzat Yeraliyeva, Guenter Froeschl, Michael Hoelscher, Stefan Frey, Edith Wagner, Lukas Peintner and Sandra Essbauer

Viruses 2022, 14(6), 1258; https://doi.org/10.3390/v14061258 - 09 Jun 2022

Cited by 2 | Viewed by 2130

Abstract

Orthohantaviruses are zoonotic pathogens that play a significant role in public health. These viruses can cause haemorrhagic fever with renal syndrome in Eurasia. In the Republic of Kazakhstan, the first human cases were registered in the year 2000 in the West Kazakhstan region. [...] Read more.

Orthohantaviruses are zoonotic pathogens that play a significant role in public health. These viruses can cause haemorrhagic fever with renal syndrome in Eurasia. In the Republic of Kazakhstan, the first human cases were registered in the year 2000 in the West Kazakhstan region. Small mammals can be reservoirs of orthohantaviruses. Previous studies showed orthohantavirus antigens in wild-living small mammals in four districts of West Kazakhstan. Clinical studies suggested that there might be further regions with human orthohantavirus infections in Kazakhstan, but genetic data of orthohantaviruses in natural foci are limited. The aim of this study was to investigate small mammals for the presence of orthohantaviruses by molecular biological methods and to provide a phylogenetic characterization of the circulating strains in Kazakhstan. Small mammals were trapped at 19 sites in West Kazakhstan, four in Almaty region and at seven sites around Almaty city during all seasons of 2018 and 2019. Lung tissues of small mammals were homogenized and RNA was extracted. Orthohantavirus RT-PCR assays were applied for detection of partial S and L segment sequences. Results were compared to published fragments. In total, 621 small mammals from 11 species were analysed. Among the collected small mammals, 2.4% tested positive for orthohantavirus RNA, one sample from West Kazakhstan and 14 samples from Almaty region. None of the rodents caught in Almaty city were infected. Sequencing parts of the small (S) and large (L) segments specified Tula virus (TULV) in these two regions. Our data show that geographical distribution of TULV is more extended as previously thought. The detected sequences were found to be split in two distinct genetic clusters of TULV in West Kazakhstan and Almaty region. TULV was detected in the common vole (Microtus arvalis) and for the first time in two individuals of the forest dormouse (Dryomys nitedula), interpreted as a spill-over infection in Kazakhstan. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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12 pages, 1292 KiB

Open AccessArticle

Detection of Lassa Virus-Reactive IgG Antibodies in Wild Rodents: Validation of a Capture Enzyme-Linked Immunological Assay

by Hugo Soubrier, Umaru Bangura, Chris Hoffmann, Ayodeji Olayemi, Adetunji Samuel Adesina, Stephan Günther, Lisa Oestereich and Elisabeth Fichet-Calvet

Viruses 2022, 14(5), 993; https://doi.org/10.3390/v14050993 - 07 May 2022

Cited by 1 | Viewed by 2406

Abstract

The aim of this study was to evaluate the use of a capture enzyme-linked immunosorbent assay (ELISA) for the detection of LASV-reactive IgG antibodies in Mastomys rodents. The assay was used for laboratory-bred Mastomys rodents, as well as for animals caught in the [...] Read more.

The aim of this study was to evaluate the use of a capture enzyme-linked immunosorbent assay (ELISA) for the detection of LASV-reactive IgG antibodies in Mastomys rodents. The assay was used for laboratory-bred Mastomys rodents, as well as for animals caught in the wild in various regions of West Africa. The ELISA reached an accuracy of 97.1% in samples of known exposure, and a comparison to an immunofluorescence assay (IFA) revealed a very strong agreement between the ELISA and IFA results (Cohen’s kappa of 0.81). The agreement is valid in Nigeria, and in Guinea and Sierra Leone where the lineages II and IV are circulating, respectively. Altogether, these results indicate that this capture ELISA is suitable for LASV IgG serostatus determination in Mastomys rodents as an alternative to IFA. This assay will be a strong, accurate, and semi-quantitative alternative for rodent seroprevalence studies that does not depend on biosafety level 4 infrastructures, providing great benefits for ecology and epidemiology studies of Lassa fever, a disease listed on the Research and Development Blueprint of the WHO. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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18 pages, 3879 KiB

Open AccessArticle

The Bank Vole (Clethrionomys glareolus)—Small Animal Model for Hepacivirus Infection

by Susanne Röhrs, Lineke Begeman, Beate K. Straub, Mariana Boadella, Dennis Hanke, Kerstin Wernike, Stephan Drewes, Bernd Hoffmann, Markus Keller, Jan Felix Drexler, Christian Drosten, Dirk Höper, Thijs Kuiken, Rainer G. Ulrich and Martin Beer

Viruses 2021, 13(12), 2421; https://doi.org/10.3390/v13122421 - 03 Dec 2021

Cited by 4 | Viewed by 2123

Abstract

Many people worldwide suffer from hepatitis C virus (HCV) infection, which is frequently persistent. The lack of efficient vaccines against HCV and the unavailability of or limited compliance with existing antiviral therapies is problematic for health care systems worldwide. Improved small animal models [...] Read more.

Many people worldwide suffer from hepatitis C virus (HCV) infection, which is frequently persistent. The lack of efficient vaccines against HCV and the unavailability of or limited compliance with existing antiviral therapies is problematic for health care systems worldwide. Improved small animal models would support further hepacivirus research, including development of vaccines and novel antivirals. The recent discovery of several mammalian hepaciviruses may facilitate such research. In this study, we demonstrated that bank voles (Clethrionomys glareolus) were susceptible to bank vole-associated Hepacivirus F and Hepacivirus J strains, based on the detection of hepaciviral RNA in 52 of 55 experimentally inoculated voles. In contrast, interferon α/β receptor deficient C57/Bl6 mice were resistant to infection with both bank vole hepaciviruses (BvHVs). The highest viral genome loads in infected voles were detected in the liver, and viral RNA was visualized by in situ hybridization in hepatocytes, confirming a marked hepatotropism. Furthermore, liver lesions in infected voles resembled those of HCV infection in humans. In conclusion, infection with both BvHVs in their natural hosts shares striking similarities to HCV infection in humans and may represent promising small animal models for this important human disease. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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Review

Jump to: Research, Other

28 pages, 1364 KiB

Open AccessReview

The Virus–Host Interplay in Junín Mammarenavirus Infection

by Giovanna Lucrecia Gallo, Nora López and María Eugenia Loureiro

Viruses 2022, 14(6), 1134; https://doi.org/10.3390/v14061134 - 24 May 2022

Cited by 8 | Viewed by 2801

Abstract

Junín virus (JUNV) belongs to the Arenaviridae family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports [...] Read more.

Junín virus (JUNV) belongs to the Arenaviridae family and is the causative agent of Argentine hemorrhagic fever (AHF), a severe human disease endemic to agricultural areas in Argentina. At this moment, there are no effective antiviral therapeutics to battle pathogenic arenaviruses. Cumulative reports from recent years have widely provided information on cellular factors playing key roles during JUNV infection. In this review, we summarize research on host molecular determinants that intervene in the different stages of the viral life cycle: viral entry, replication, assembly and budding. Alongside, we describe JUNV tight interplay with the innate immune system. We also review the development of different reverse genetics systems and their use as tools to study JUNV biology and its close teamwork with the host. Elucidating relevant interactions of the virus with the host cell machinery is highly necessary to better understand the mechanistic basis beyond virus multiplication, disease pathogenesis and viral subversion of the immune response. Altogether, this knowledge becomes essential for identifying potential targets for the rational design of novel antiviral treatments to combat JUNV as well as other pathogenic arenaviruses. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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Other

Jump to: Research, Review

7 pages, 756 KiB

Open AccessBrief Report

HuH-7-Lunet BLR Cells Propagate Rat Hepatitis E Virus (HEV) in a Cell Culture System Optimized for HEV

by Mathias Schemmerer, Monika Erl and Jürgen J. Wenzel

Viruses 2022, 14(5), 1116; https://doi.org/10.3390/v14051116 - 23 May 2022

Cited by 4 | Viewed by 2417

Abstract

The family Hepeviridae comprises the species Orthohepevirus A–D (HEV-A to -D). HEV-C genotype 1 (HEV-C1, rat HEV) is able to infect humans. This study investigated whether an optimized HEV-A cell culture system is able to propagate the cell culture-derived rat HEV, and if [...] Read more.

The family Hepeviridae comprises the species Orthohepevirus A–D (HEV-A to -D). HEV-C genotype 1 (HEV-C1, rat HEV) is able to infect humans. This study investigated whether an optimized HEV-A cell culture system is able to propagate the cell culture-derived rat HEV, and if de novo isolation of the virus from rat liver is possible. We tested the liver carcinoma cell lines PLC/PRF/5, HuH-7, and HuH-7-Lunet BLR for their susceptibility to HEV-C1 strains. Cells were infected with the cell culture-derived HEV-C1 strain R63 and rat liver-derived strain R68. Cells were maintained in MEMM medium, which was refreshed every 3–4 days. The viral load of HEV-C1 was determined by RT-qPCR in the supernatant and expressed as genome copies per mL (c/mL). Rat HEV replication was most efficient in the newly introduced HuH-7-Lunet BLR cell line. Even if the rat HEV isolate had been pre-adapted to PLC/PRF/5 by multiple passages, replication in HuH-7-Lunet BLR was still at least equally effective. Only HuH-7-Lunet BLR cells were susceptible to the isolation of HEV-C1 from the liver homogenate. These results suggest HuH-7-Lunet BLR as the most permissive cell line for rat HEV. Our HEV-C1 cell culture system may be useful for basic research, the animal-free generation of large amounts of the virus as well as for the testing of antiviral compounds and drugs. Full article

(This article belongs to the Special Issue Rodent-Borne Viruses 2.0)

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