ICTV Virus Taxonomy Profile: Hantaviridae 2024.

Hantaviridae is a family for negative-sense RNA viruses with genomes of about 10.5-14.6 kb. These viruses are maintained in and/or transmitted by fish, reptiles, and mammals. Several orthohantaviruses can infect humans, causing mild, severe, and sometimes-fatal diseases. Hantavirids produce enveloped virions containing three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), a glycoprotein precursor (GPC), and a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Hantaviridae, which is available at ictv.global/report/hantaviridae.

Identification and evaluation of antiviral activity of novel compounds targeting SARS-CoV-2 virus by enzymatic and antiviral assays, and computational analysis.

The viral genome of the SARS-CoV-2 coronavirus, the aetiologic agent of COVID-19, encodes structural, non-structural, and accessory proteins. Most of these components undergo rapid genetic variations, though to a lesser extent the essential viral proteases. Consequently, the protease and/or deubiquitinase activities of the cysteine proteases Mpro and PLpro became attractive targets for the design of antiviral agents. Here, we develop and evaluate new bis(benzylidene)cyclohexanones (BBC) and identify potential antiviral compounds. Three compounds were found to be effective in reducing the SARS-CoV-2 load, with EC50 values in the low micromolar concentration range. However, these compounds also exhibited inhibitory activity IC50 against PLpro at approximately 10-fold higher micromolar concentrations. Although originally developed as PLpro inhibitors, the comparison between IC50 and EC50 of BBC indicates that the mechanism of their in vitro antiviral activity is probably not directly related to inhibition of viral cysteine proteases. In conclusion, our study has identified new potential noncytotoxic antiviral compounds suitable for in vivo testing and further improvement.

VirPool: model-based estimation of SARS-CoV-2 variant proportions in wastewater samples.

BACKGROUND: The genomes of SARS-CoV-2 are classified into variants, some of which are monitored as variants of concern (e.g. the Delta variant B.1.617.2 or Omicron variant B.1.1.529). Proportions of these variants circulating in a human population are typically estimated by large-scale sequencing of individual patient samples. Sequencing a mixture of SARS-CoV-2 RNA molecules from wastewater provides a cost-effective alternative, but requires methods for estimating variant proportions in a mixed sample. RESULTS: We propose a new method based on a probabilistic model of sequencing reads, capturing sequence diversity present within individual variants, as well as sequencing errors. The algorithm is implemented in an open source Python program called VirPool. We evaluate the accuracy of VirPool on several simulated and real sequencing data sets from both Illumina and nanopore sequencing platforms, including wastewater samples from Austria and France monitoring the onset of the Alpha variant. CONCLUSIONS: VirPool is a versatile tool for wastewater and other mixed-sample analysis that can handle both short- and long-read sequencing data. Our approach does not require pre-selection of characteristic mutations for variant profiles, it is able to use the entire length of reads instead of just the most informative positions, and can also capture haplotype dependencies within a single read.

A SARS-CoV-2 mutant from B.1.258 lineage with ∆H69/∆V70 deletion in the Spike protein circulating in Central Europe in the fall 2020.

SARS-CoV-2 mutants carrying the ∆H69/∆V70 deletion in the amino-terminal domain of the Spike protein emerged independently in at least six lineages of the virus (namely, B.1.1.7, B.1.1.298, B.1.160, B.1.177, B.1.258, B.1.375). We analyzed SARS-CoV-2 samples collected from various regions of Slovakia between November and December 2020 that were presumed to contain B.1.1.7 variant due to drop-out of the Spike gene target in an RT-qPCR test caused by this deletion. Sequencing of these samples revealed that although in some cases the samples were indeed confirmed as B.1.1.7, a substantial fraction of samples contained another ∆H69/∆V70 carrying mutant belonging to the lineage B.1.258, which has been circulating in Central Europe since August 2020, long before the import of B.1.1.7. Phylogenetic analysis shows that the early sublineage of B.1.258 acquired the N439K substitution in the receptor-binding domain (RBD) of the Spike protein and, later on, also the deletion ∆H69/∆V70 in the Spike N-terminal domain (NTD). This variant was particularly common in several European countries including the Czech Republic and Slovakia but has been quickly replaced by B.1.1.7 early in 2021.

Seroprevalence of SARS-CoV-2 IgG antibodies in the staff of the Slovak Academy of Sciences in response to COVID-19 and/or vaccination: situation in August 2021.

Cross-sectional seroprevalence study of SARS-CoV-2 IgG antibodies was accomplished in the Slovak Academy of Sciences to inform authorities of research institutions about the situation at their workplaces, to assess the risk of next exposure to SARS-CoV-2, and to guide decisions on institutional measures sustaining essential research in evolving epidemic situation. Study participants provided informed consent, anamnestic information, and self-collected dry blood spot samples that were analyzed by ELISA for SARS-CoV-2 S protein-specific IgG antibodies. Relative antibody levels detected in 1928 subjects showed seroprevalence of 84.13% and led to the following main findings consistent with the current knowledge: (1) mRNA-based vaccines induce better humoral response compared to adenovirus vaccines, (2) antibody levels reflect severity of COVID-19 symptoms, (3) post-COVID vaccination results in marked elevation of IgG levels particularly in asymptomatic and mild cases, (4) antibody levels decrease with increasing time elapsed from vaccination or COVID-19. In addition, data sorting to distinct research institutes and their clustering to three principal scientific sections of the Slovak Academy of Sciences revealed marked differences in seroprevalence, and allowed to identify workplaces with relatively high seropositivity and response rate that can potentially provide a safer working environment than those, where seroprevalence was low or unknown due to low participation. Thus, findings of this study can have direct implications on management decisions during the next pandemic development, with the necessity to keep in mind the phenomenon of time-dependent immunity waning and current spread of more contagious Delta variant of SARS-CoV-2. Keywords: SARS-CoV-2 coronavirus; COVID-19; spike protein; seroprevalence; antibodies; vaccination.

Strengthening the Interaction of the Virology Community with the International Committee on Taxonomy of Viruses (ICTV) by Linking Virus Names and Their Abbreviations to Virus Species.

The International Committee on Taxonomy of Viruses (ICTV) is tasked with classifying viruses into taxa (phyla to species) and devising taxon names. Virus names and virus name abbreviations are currently not within the ICTV's official remit and are not regulated by an official entity. Many scientists, medical/veterinary professionals, and regulatory agencies do not address evolutionary questions nor are they concerned with the hierarchical organization of the viral world, and therefore, have limited use for ICTV-devised taxa. Instead, these professionals look to the ICTV as an expert point source that provides the most current taxonomic affiliations of viruses of interests to facilitate document writing. These needs are currently unmet as an ICTV-supported, easily searchable database that includes all published virus names and abbreviations linked to their taxa is not available. In addition, in stark contrast to other biological taxonomic frameworks, virus taxonomy currently permits individual species to have several members. Consequently, confusion emerges among those who are not aware of the difference between taxa and viruses, and because certain well-known viruses cannot be located in ICTV publications or be linked to their species. In addition, the number of duplicate names and abbreviations has increased dramatically in the literature. To solve this conundrum, the ICTV could mandate listing all viruses of established species and all reported unclassified viruses in forthcoming online ICTV Reports and create a searchable webpage using this information. The International Union of Microbiology Societies could also consider changing the mandate of the ICTV to include the nomenclature of all viruses in addition to taxon considerations. With such a mandate expansion, official virus names and virus name abbreviations could be catalogued and virus nomenclature could be standardized. As a result, the ICTV would become an even more useful resource for all stakeholders in virology.

Hemorrhagic Fever with Renal Syndrome, Russia.

In Russia, 131,590 cases of hemorrhagic fever with renal syndrome caused by 6 different hantaviruses were reported during 2000-2017. Most cases, 98.4%, were reported in western Russia. The average case-fatality rate was 0.4%, and strong regional differences were seen, depending on the predominant virus type.

Taxonomy of the order Bunyavirales: update 2019.

In February 2019, following the annual taxon ratification vote, the order Bunyavirales was amended by creation of two new families, four new subfamilies, 11 new genera and 77 new species, merging of two species, and deletion of one species. This article presents the updated taxonomy of the order Bunyavirales now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Taxonomy of the order Bunyavirales: second update 2018.

In October 2018, the order Bunyavirales was amended by inclusion of the family Arenaviridae, abolishment of three families, creation of three new families, 19 new genera, and 14 new species, and renaming of three genera and 22 species. This article presents the updated taxonomy of the order Bunyavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Reassortment events in the evolution of hantaviruses.

Hantaviruses (order Bunyavirales, family Hantaviridae), known as important zoonotic human pathogens, possess the capacity to exchange genome segments via genetic reassortment due to their tri-segmented genome. Although not as frequent as in the arthropod-borne bunyaviruses, reports indicating reassortment events in the evolution of hantaviruses have been recently accumulating. The intra- and inter-lineage reassortment between closely related variants has been repeatedly reported for several hantaviruses including the rodent-borne human pathogens such as Sin Nombre virus, Puumala virus, Dobrava-Belgrade virus, or Hantaan virus as well as for the more recently recognized shrew-borne hantaviruses, Imjin and Seewis. Reassortment between more distantly related viruses was rarely found but seems to play a beneficial role in the process of crossing the host species barriers. Besides the findings based on phylogenetic studies of naturally occurring strains, hantavirus reassortants were generated also in in vitro studies. Interestingly, only reassortants with exchanged M segments could be generated suggesting that a high degree of genetic compatibility is required for the S and L segments while the exchange of M segment is better tolerated or is particularly beneficial. Altogether, the numerous reports on hantavirus reassortment, summarized in this review, clearly demonstrate that reassortment events play a significant role in hantavirus evolution and contributed to the currently recognized hantavirus diversity.

Phylogenetic analysis of Puumala virus strains from Central Europe highlights the need for a full-genome perspective on hantavirus evolution.

Puumala virus (PUUV), carried by bank voles (Myodes glareolus), is the medically most important hantavirus in Central and Western Europe. In this study, a total of 523 bank voles (408 from Germany, 72 from Slovakia, and 43 from Czech Republic) collected between the years 2007-2012 were analyzed for the presence of hantavirus RNA. Partial PUUV genome segment sequences were obtained from 51 voles. Phylogenetic analyses of all three genome segments showed that the newfound strains cluster with other Central and Western European PUUV strains. The new sequences from Sumava (Bohemian Forest), Czech Republic, are most closely related to the strains from the neighboring Bavarian Forest, a known hantavirus disease outbreak region. Interestingly, the Slovak strains clustered with the sequences from Bohemian and Bavarian Forests only in the M but not S segment analyses. This well-supported topological incongruence suggests a segment reassortment event or, as we analyzed only partial sequences, homologous recombination. Our data highlight the necessity of sequencing all three hantavirus genome segments and of a broader bank vole screening not only in recognized endemic foci but also in regions with no reported human hantavirus disease cases.

Human Infections by Non-Rodent-Associated Hantaviruses in Africa.

Various hantaviruses have been discovered in unconventional hosts (shrews and bats) in Africa. Up to now, it was unknown whether these viruses pose a threat for human health. In this study, using newly established serological assays, we demonstrated evidence of shrew-borne hantavirus infections in humans from Côte d'Ivoire and Gabon.

Clinical characterization of two severe cases of hemorrhagic fever with renal syndrome (HFRS) caused by hantaviruses Puumala and Dobrava-Belgrade genotype Sochi.

BACKGROUND: Hantavirus disease belongs to the emerging infections. The clinical picture and severity of infections differ between hantavirus species and may even vary between hantavirus genotypes. The mechanisms that lead to the broad variance of severity in infected patients are not completely understood. Host- and virus-specific factors are considered. CASE PRESENTATION: We analyzed severe cases of hantavirus disease in two young women. The first case was caused by Puumala virus (PUUV) infection in Germany; the second case describes the infection with Dobrava-Belgrade virus (DOBV) in Russia. Symptoms, laboratory parameters and cytokine levels were analyzed and compared between the two patients. Serological and sequence analysis revealed that PUUV was the infecting agent for the German patient and the infection of the Russian patient was caused by Dobrava-Belgrade virus genotype Sochi (DOBV-Sochi). The symptoms in the initial phase of the diseases did not differ noticeably between both patients. However, deterioration of laboratory parameter values was prolonged and stronger in DOBV-Sochi than in PUUV infection. Circulating endothelial progenitor cells (cEPCs), known to be responsible for endothelial repair, were mobilized in both infections. Striking differences were observed in the temporal course and level of cytokine upregulation. Levels of angiopoietin-2 (Ang-2), vascular endothelial growth factor (VEGF), and stromal derived factor-1 (SDF-1α) were increased in both infections; but, sustained and more pronounced elevation was observed in DOBV-Sochi infection. CONCLUSIONS: Severe hantavirus disease caused by different hantavirus species did not differ in the general symptoms and clinical characteristics. However, we observed a prolonged clinical course and a late and enhanced mobilization of cytokines in DOBV-Sochi infection. The differences in cytokine deregulation may contribute to the observed variation in the clinical course.

Life-Threatening Sochi Virus Infections, Russia.

Sochi virus was recently identified as a new hantavirus genotype carried by the Black Sea field mouse, Apodemus ponticus. We evaluated 62 patients in Russia with Sochi virus infection. Most clinical cases were severe, and the case-fatality rate was as high as 14.5%.

Novel Arenavirus Isolates from Namaqua Rock Mice, Namibia, Southern Africa.

Arenaviruses are feared as agents that cause viral hemorrhagic fevers. We report the identification, isolation, and genetic characterization of 2 novel arenaviruses from Namaqua rock mice in Namibia. These findings extend knowledge of the distribution and diversity of arenaviruses in Africa.

Molekulare Identifikation von Hantaviren in neuen Wirten.

In addition to classical virus isolation in cell culture, the molecular detection of new virus variants by PCR techniques allows broader epidemiological insights into the world of viral pathogens. For the detection of hantaviruses-zoonotic viruses leading to fever and organ failure in humans-we developed a genus-wide nested RT-PCR format, which enables the discovery of new members within this virus genus. The methodological approach allowed the demonstration of first hantaviruses from Africa and revealed new hantavirus reservoir hosts, as shrews, moles, and bats.

Full genome sequences and preliminary molecular characterization of three tick-borne encephalitis virus strains isolated from ticks and a bank vole in Slovak Republic.

The full genome sequences of three tick-borne encephalitis virus strains, two isolated from Ixodes ricinus ticks and one from the brain of a bank vole, Myodes glareolus, originating from the Slovak Republic were determined. Nucleotide sequences were found to be very similar (>99.5 % nt-identity) with only one distinct amino acid (aa) difference to each other. They all shared 30 aa-changes when compared to type strain Neudoerfl, isolated in neighboring Austria. An internal poly(A)-stretch similar to that of strain Neudoerfl was found only in TBEV strain 114 from a tick. Despite this heterogeneity in the 3'-NCR, the high level of sequence identity was striking, indicating a low rate of nucleotide substitutions of TBEV strains in Slovakia and no obvious relation to the host species.

Molecular phylogeography of tick-borne encephalitis virus in central Europe.

In order to obtain a better understanding of tick-borne encephalitis virus (TBEV) strain movements in central Europe the E gene sequences of 102 TBEV strains collected from 1953 to 2011 at 38 sites in the Czech Republic, Slovakia, Austria and Germany were determined. Bayesian analysis suggests a 350-year history of evolution and spread in central Europe of two main lineages, A and B. In contrast to the east to west spread at the Eurasian continent level, local central European spreading patterns suggest historic west to east spread followed by more recent east to west spread. The phylogenetic and network analyses indicate TBEV ingressions from the Czech Republic and Slovakia into Germany via landscape features (Danube river system), biogenic factors (birds, red deer) and anthropogenic factors. The identification of endemic foci showing local genetic diversity is of paramount importance to the field as these will be a prerequisite for in-depth analysis of focal TBEV maintenance and long-distance TBEV spread.

Sangassou virus, the first hantavirus isolate from Africa, displays genetic and functional properties distinct from those of other murinae-associated hantaviruses.

We have discovered the first indigenous African hantavirus, Sangassou virus (SANGV). The virus was isolated from an African wood mouse (Hylomyscus simus), trapped in a forest habitat in Guinea, West Africa. Here, we report on the characterization of the genetic and functional properties of the virus. The complete genome of SANGV was determined and showed typical hantavirus organization. The small (S), medium (M), and large (L) genome segments containing genes encoding nucleocapsid protein, two envelope glycoproteins, and viral polymerase were found to be 1,746, 3,650, and 6,531 nucleotides long, respectively. The exact 5' and 3' termini for all three segments of the SANGV genome were determined and were predicted to form the panhandle structures typical of bunyaviruses. Phylogenetic analyses of all three segment sequences confirmed SANGV as a Murinae-associated hantavirus most closely related to the European Dobrava-Belgrade virus. We showed, however, that SANGV uses ß(1) integrin rather than ß(3) integrin and decay-accelerating factor (DAF)/CD55 as an entry receptor. In addition, we demonstrated a strong induction of type III lambda interferon (IFN-λ) expression in type I IFN-deficient Vero E6 cells by SANGV. These properties are unique within Murinae-associated hantaviruses and make the virus useful in comparative studies focusing on hantavirus pathogenesis.

Seroepidemiological study reveals regional co-occurrence of Lassa- and Hantavirus antibodies in Upper Guinea, West Africa.

OBJECTIVES: To assess the public health relevance of Lassa arenavirus and hantavirus infections in a subpopulation of recently febrile patients. METHODS: In a human seroprevalence study, we enrolled 253 participants on the basis of reported high fever during the last 3 months. They represented roughly 20% of the population of Bantou and Tanganya villages. Comprehensive serological screening and confirmatory assays (enzyme-linked immunosorbent assay, immunofluorescence assay, Western blot analysis) with several Lassa virus and hantavirus antigens were used to ensure high specificity and broad detection capacity. RESULTS: We found a Lassa IgG prevalence of 40.3% (102/253) and a hantavirus IgG prevalence of 1.2% (3/253). The Lassa IgM prevalence reached 2.8% (7/253). CONCLUSIONS: High Lassa virus seroprevalence in recently febrile patients indicates that Lassa fever is a significant public health problem in the region. Human hantavirus infections also occur in the region but their public health relevance remains to be determined.