Lymphocytic choriomeningitis, Ljungan and orthopoxvirus seroconversions in patients hospitalized due to acute Puumala hantavirus infection

Background: The emergence and re-emergence of zoonotic and vector-borne diseases are increasing in Europe. Prominent rodent-borne zoonotic viruses include Puumala hantavirus (PUUV; the causative agent of nephropathia epidemica, NE), lymphocytic choriomeningitis virus (LCMV), and orthopoxviruses (OPV). In addition, Ljungan virus (LV) is considered a potentially zoonotic virus. Objective: The aim of this study was to compare clinical picture between acute PUUV patients with and without additional rodent-borne viral infections, to investigate if concurrent infections influence disease severity. Study design: We evaluated seroprevalence of and seroconversions to LCMV, LV and OPV in 116 patients hospitalized for NE. Clinical and laboratory variables were closely monitored during hospital care. Results: A total of five LCMV, 15 LV, and one OPV seroconversions occurred. NE patients with LCMV seroconversions were younger, and had lower plasma creatinine concentrations and platelet counts than patients without LCMV seroconversions. No differences occurred in clinical or laboratory findings between patients with and without seroconversions to LV and OPV. We report, for the first time, LCMV seroprevalence in Finland, with 8.5% of NE patients seropositive for this virus. Seroprevalences for LV and OPV were 47.8% and 32.4%, respectively. Conclusion: Cases with LCMV seroconversions were statistically younger, had milder acute kidney injury and more severe thrombocytopenia than patients without LCMV. However, the low number of seroconversion cases precludes firm conclusions. Concurrent LV or OPV infections do not appear to influence clinical picture for NE patients. (C) 2016 Elsevier B.V. All rights reserved.Peer reviewe

Evolutionary Relationships of Ljungan Virus Variants Circulating in Multi-Host Systems across Europe

The picornavirus named ‘Ljungan virus’ (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission

Evolutionary Relationships of Ljungan Virus Variants Circulating in Multi-Host Systems across Europe

The picornavirus named ‘Ljungan virus’ (LV, species Parechovirus B) has been detected in a dozen small mammal species from across Europe, but detailed information on its genetic diversity and host specificity is lacking. Here, we analyze the evolutionary relationships of LV variants circulating in free-living mammal populations by comparing the phylogenetics of the VP1 region (encoding the capsid protein and associated with LV serotype) and the 3Dpol region (encoding the RNA polymerase) from 24 LV RNA-positive animals and a fragment of the 5′ untranslated region (UTR) sequence (used for defining strains) in sympatric small mammals. We define three new VP1 genotypes: two in bank voles (Myodes glareolus) (genotype 8 from Finland, Sweden, France, and Italy, and genotype 9 from France and Italy) and one in field voles (Microtus arvalis) (genotype 7 from Finland). There are several other indications that LV variants are host-specific, at least in parts of their range. Our results suggest that LV evolution is rapid, ongoing and affected by genetic drift, purifying selection, spillover and host evolutionary history. Although recent studies suggest that LV does not have zoonotic potential, its widespread geographical and host distribution in natural populations of well-characterized small mammals could make it useful as a model for studying RNA virus evolution and transmission

Geographical Distribution and Genetic Diversity of Bank Vole Hepaciviruses in Europe

The development of new diagnostic methods resulted in the discovery of novel hepaciviruses in wild populations of the bank vole (Myodes glareolus, syn. Clethrionomys glareolus). The naturally infected voles demonstrate signs of hepatitis similar to those induced by hepatitis C virus (HCV) in humans. The aim of the present research was to investigate the geographical distribution of bank vole-associated hepaciviruses (BvHVs) and their genetic diversity in Europe. Real-time reverse transcription polymerase chain reaction (RT-qPCR) screening revealed BvHV RNA in 442 out of 1838 (24.0%) bank voles from nine European countries and in one of seven northern red-backed voles (Myodes rutilus, syn. Clethrionomys rutilus). BvHV RNA was not found in any other small mammal species (n = 23) tested here. Phylogenetic and isolation-by-distance analyses confirmed the occurrence of both BvHV species (Hepacivirus F and Hepacivirus J) and their sympatric occurrence at several trapping sites in two countries. The broad geographical distribution of BvHVs across Europe was associated with their presence in bank voles of different evolutionary lineages. The extensive geographical distribution and high levels of genetic diversity of BvHVs, as well as the high population fluctuations of bank voles and occasional commensalism in some parts of Europe warrant future studies on the zoonotic potential of BvHVs.Peer reviewe

Is rodent-borne Ljungan virus responsible for mortality in migrating Norwegian lemmings (Lemmus lemmus)?

In 1998, a new virus was isolated in wild populations of bank voles (Myodes glareolus) in Sweden. The suspected pathogen was named the “Ljungan virus” (LV), after the river near the site of its discovery. Later, it was also detected in voles in the United States and Denmark, and more recently in the UK and Italy. Interest in LV stems from reports that this virus may be associated with human fetal death and malformations. Some authors maintain that LV should be considered a potential zoonotic agent (i.e. a pathogen carried by wild animals that can infect and cause disease in humans), while others are distinctly more skeptical. Recent optimization and testing of a serological technique using LV-positive rodent samples show that humans can apparently be infected with LV, or an LV-type virus, but its ability to cause symptoms has not been definitively proven, and species-specificity has not been investigated

PCR prevalence of rodent-borne Ljungan virus across Europe

Since its discovery in Swedish bank voles (Myodes glareolus) in the 1990s (Niklasson et al., 1999), interest in the Ljungan (picorna-)virus (LV) has grown as a result of a suggested association of the virus with some human pathologies, and because serological and neutralization tests have confirmed that humans are exposed to LV (38% in Jääskeläinen et al., 2013). LV infection induces fetal malformations and diabetes-like symptoms in laboratory mice, and since LV also causes disease in some wild rodents, it may have a role in small mammal cycles. Hence, LV epidemiology is potentially of global interest. Although LV has been noted in single populations of several rodent species in Denmark, the USA, Germany, Italy, Finland and the UK (Johansson et al., 2003; Hauffe et al., 2010; Kallies, 2010 and references therein; Jääskeläinen et al., 2013; Salisbury et al., 2014), this is the first systematic screening of LV across the EU, especially in the bank vole, but also in other small mammals, including shrews and commensal species. In all, 15 different species from nine European countries were sampled as part of the EU FP7 project EDENext. Using an LV-specific RT-PCR method (Donoso-Mantke et al., 2007), 1509 liver samples stored at -80°C were screened for LV, including 831 bank voles. All amplified fragments were sequenced for confirmation. LV-positive samples were found in all countries with significant sample sizes, and in most species, including house mice, but not black rats. Overall PCR prevalence in bank voles was about 16% (range 0-50% per population). We added eight new species to the list of LV hosts, including the red squirrel (Sciurus vulgaris), and a number of voles and shrews. Our study suggests that LV has a wide geographical and host distribution