IFIH1 loss of function predisposes to inflammatory and SARS-CoV-2-related infectious diseases.

The IFIH1 gene, encoding melanoma differentiation-associated protein 5 (MDA5), is an indispensable innate immune regulator involved in the early detection of viral infections. Previous studies described MDA5 dysregulation in weakened immunological responses, and increased susceptibility to microbial infections and autoimmune disorders. Monoallelic gain-of-function of the IFIH1 gene has been associated with multisystem disorders, namely Aicardi-Goutieres and Singleton-Merten syndromes, while biallelic loss causes immunodeficiency. In this study, nine patients suffering from recurrent infections, inflammatory diseases, severe COVID-19 or multisystem inflammatory syndrome in children (MIS-C) were identified with putative loss-of-function IFIH1 variants by whole-exome sequencing. All patients revealed signs of lymphopaenia and an increase in inflammatory markers, including CRP, amyloid A, ferritin and IL-6. One patient with a pathogenic homozygous variant c.2807+1G>A was the most severe case showing immunodeficiency and glomerulonephritis. The c.1641+1G>C variant was identified in the heterozygous state in patients suffering from periodic fever, COVID-19 or MIS-C, while the c.2016delA variant was identified in two patients with inflammatory bowel disease or MIS-C. There was a significant association between IFIH1 monoallelic loss of function and susceptibility to infections in males. Expression analysis showed that PBMCs of one patient with a c.2016delA variant had a significant decrease in ISG15, IFNA and IFNG transcript levels, compared to normal PBMCs, upon stimulation with Poly(I:C), suggesting that MDA5 receptor truncation disrupts the immune response. Our findings accentuate the implication of rare monogenic IFIH1 loss-of-function variants in altering the immune response, and severely predisposing patients to inflammatory and infectious diseases, including SARS-CoV-2-related disorders.

Association of Dromedary Camels and Camel Ticks with Reassortant Crimean-Congo Hemorrhagic Fever Virus, United Arab Emirates.

We previously detected a potentially novel reassortant of Crimean-Congo hemorrhagic fever virus in camels at the largest livestock market in the United Arab Emirates. A broader survey of large mammals at the site indicated zoonotic transmission is associated with dromedaries and camel ticks. Seroprevalence in cattle, sheep, and goats is minimal.

ICTV Virus Taxonomy Profile: Bornaviridae.

Members of the family Bornaviridae produce enveloped virions containing a linear negative-sense non-segmented RNA genome of about 9 kb. Bornaviruses are found in mammals, birds, reptiles and fish. The most-studied viruses with public health and veterinary impact are Borna disease virus 1 and variegated squirrel bornavirus 1, both of which cause fatal encephalitis in humans. Several orthobornaviruses cause neurological and intestinal disorders in birds, mostly parrots. Endogenous bornavirus-like sequences occur in the genomes of various animals. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Bornaviridae, which is available at ictv.global/report/bornaviridae.

Crimean-Congo Hemorrhagic Fever Virus Endemicity in United Arab Emirates, 2019.

We conducted a cross-sectional survey of Crimean-Congo hemorrhagic fever virus (CCHFV) in dromedary camels and attached ticks at 3 locations in the United Arab Emirates. Results revealed a high prevalence of CCHFV-reactive antibodies in camels and viral RNA in ticks and camel serum, suggesting the virus is endemic in this country.

SARS-CoV-2 Whole Genome Amplification and Sequencing for Effective Population-Based Surveillance and Control of Viral Transmission.

BACKGROUND: With the gradual reopening of economies and resumption of social life, robust surveillance mechanisms should be implemented to control the ongoing COVID-19 pandemic. Unlike RT-qPCR, SARS-CoV-2 whole genome sequencing (cWGS) has the added advantage of identifying cryptic origins of the virus, and the extent of community-based transmissions versus new viral introductions, which can in turn influence public health policy decisions. However, the practical and cost considerations of cWGS should be addressed before it is widely implemented. METHODS: We performed shotgun transcriptome sequencing using RNA extracted from nasopharyngeal swabs of patients with COVID-19, and compared it to targeted SARS-CoV-2 genome amplification and sequencing with respect to virus detection, scalability, and cost-effectiveness. To track virus origin, we used open-source multiple sequence alignment and phylogenetic tools to compare the assembled SARS-CoV-2 genomes to publicly available sequences. RESULTS: We found considerable improvement in whole genome sequencing data quality and viral detection using amplicon-based target enrichment of SARS-CoV-2. With enrichment, more than 99% of the sequencing reads mapped to the viral genome, compared to an average of 0.63% without enrichment. Consequently, an increase in genome coverage was obtained using substantially less sequencing data, enabling higher scalability and sizable cost reductions. We also demonstrated how SARS-CoV-2 genome sequences can be used to determine their possible origin through phylogenetic analysis including other viral strains. CONCLUSIONS: SARS-CoV-2 whole genome sequencing is a practical, cost-effective, and powerful approach for population-based surveillance and control of viral transmission in the next phase of the COVID-19 pandemic.

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.

Haemosporidioses in wild Eurasian blackbirds (Turdus merula) and song thrushes (T. philomelos): an in situ hybridization study with emphasis on exo-erythrocytic parasite burden.

BACKGROUND: Passerine birds are frequently infected with diverse haemosporidian parasites. While infections are traditionally considered benign in wild birds, recent studies demonstrated mortalities of passerine species due to exo-erythrocytic development of the parasites, which can damage organs in affected hosts. However, exo-erythrocytic development remains insufficiently investigated for most haemosporidian species and thus little is known about the virulence of tissue stages in wild passerine birds. The aim of the present study was to investigate natural haemosporidian infections in deceased Eurasian blackbirds (Turdus merula) and song thrushes (Turdus philomelos) and to determine parasite burden and associated histological effects. METHODS: For molecular analysis, blood and tissue samples from 306 thrushes were screened for Plasmodium, Haemoproteus and Leucocytozoon parasites by nested PCR. For the detection of parasite stages in organ samples, tissue sections were subjected to chromogenic in situ hybridization (CISH) using genus- and species-specific probes targeting the rRNAs of parasites. Exo-erythrocytic parasite burden was semi-quantitatively assessed and histological lesions were evaluated in haematoxylin-eosin-stained sections. RESULTS: By PCR, 179 of 277 Eurasian blackbirds and 15 of 29 song thrushes were positive for haemosporidians. Parasites of all three genera were detected, with Plasmodium matutinum LINN1 and Plasmodium vaughani SYAT05 showing the highest prevalence. CISH revealed significant differences in exo-erythrocytic parasite burden between lineages in Eurasian blackbirds, with P. matutinum LINN1 frequently causing high exo-erythrocytic parasite burdens in various organs that were associated with histological alterations. Song thrushes infected with P. matutinum LINN1 and birds infected with other haemosporidian lineages showed mostly low exo-erythrocytic parasite burdens. Two Eurasian blackbirds infected with Leucocytozoon sp. TUMER01 showed megalomeronts in various organs that were associated with inflammatory reactions and necroses. CONCLUSION: This study suggests that P. matutinum LINN1, a common lineage among native thrushes, regularly causes high exo-erythrocytic parasite burdens in Eurasian blackbirds, which may result in disease and mortalities, indicating its high pathogenic potential. The findings further illustrate that the same parasite lineage may show different levels of virulence in related bird species which should be considered when assessing the pathogenicity of haemosporidian parasite species. Finally, the study provides evidence of virulent Leucocytozoon sp. TUMER01 infections in two Eurasian blackbirds caused by megalomeront formation.

West Nile and Usutu Virus Infections and Challenges to Blood Safety in the European Union.

West Nile virus (WNV) and Usutu virus (USUV) circulate in several European Union (EU) countries. The risk of transfusion-transmitted West Nile virus (TT-WNV) has been recognized, and preventive blood safety measures have been implemented. We summarized the applied interventions in the EU countries and assessed the safety of the blood supply by compiling data on WNV positivity among blood donors and on reported TT-WNV cases. The paucity of reported TT-WNV infections and the screening results suggest that blood safety interventions are effective. However, limited circulation of WNV in the EU and presumed underrecognition or underreporting of TT-WNV cases contribute to the present situation. Because of cross-reactivity between genetically related flaviviruses in the automated nucleic acid test systems, USUV-positive blood donations are found during routine WNV screening. The clinical relevance of USUV infection in humans and the risk of USUV to blood safety are unknown.

Taxonomy of the order Mononegavirales: update 2019.

In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Taxonomy of the order Mononegavirales: second update 2018.

In October 2018, the order Mononegavirales was amended by the establishment of three new families and three new genera, abolishment of two genera, and creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Possibility and Challenges of Conversion of Current Virus Species Names to Linnaean Binomials.

Botanical, mycological, zoological, and prokaryotic species names follow the Linnaean format, consisting of an italicized Latinized binomen with a capitalized genus name and a lower case species epithet (e.g., Homo sapiens). Virus species names, however, do not follow a uniform format, and, even when binomial, are not Linnaean in style. In this thought exercise, we attempted to convert all currently official names of species included in the virus family Arenaviridae and the virus order Mononegavirales to Linnaean binomials, and to identify and address associated challenges and concerns. Surprisingly, this endeavor was not as complicated or time-consuming as even the authors of this article expected when conceiving the experiment. [Arenaviridae; binomials; ICTV; International Committee on Taxonomy of Viruses; Mononegavirales; virus nomenclature; virus taxonomy.].

Increase in human West Nile and Usutu virus infections, Austria, 2018.

Between 28 June and 17 September 2018, 27 cases of human West Nile virus infections were recorded in Austria; four cases of West Nile neuroinvasive disease, 11 cases of West Nile fever, six infections detected by blood donation screening and six imported cases. In addition, 18 cases of human Usutu virus infections (all blood donors) were recorded. This is the highest number of annual infections recorded in Austria since the introduction of both viruses.

Taxonomy of the order Mononegavirales: update 2017.

In 2017, the order Mononegavirales was expanded by the inclusion of a total of 69 novel species. Five new rhabdovirus genera and one new nyamivirus genus were established to harbor 41 of these species, whereas the remaining new species were assigned to already established genera. Furthermore, non-Latinized binomial species names replaced all paramyxovirus and pneumovirus species names, thereby accomplishing application of binomial species names throughout the entire order. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Usutu virus infections among blood donors, Austria, July and August 2017 - Raising awareness for diagnostic challenges.

Between July and August 2017, seven of 12,047 blood donations from eastern Austria, reacted positive to West Nile virus (WNV) in the cobas test (Roche). Follow-up investigations revealed Usutu virus (USUV) nucleic acid in six of these. Retrospective analyses of four blood donors diagnosed as WNV-infected in 2016 showed one USUV positive. Blood transfusion services and public health authorities in USUV-endemic areas should be aware of a possible increase of human USUV infections.

West Nile virus surveillance in Europe: moving towards an integrated animal-human-vector approach.

This article uses the experience of five European countries to review the integrated approaches (human, animal and vector) for surveillance and monitoring of West Nile virus (WNV) at national and European levels. The epidemiological situation of West Nile fever in Europe is heterogeneous. No model of surveillance and monitoring fits all, hence this article merely encourages countries to implement the integrated approach that meets their needs. Integration of surveillance and monitoring activities conducted by the public health authorities, the animal health authorities and the authorities in charge of vector surveillance and control should improve efficiency and save resources by implementing targeted measures. The creation of a formal interagency working group is identified as a crucial step towards integration. Blood safety is a key incentive for public health authorities to allocate sufficient resources for WNV surveillance, while the facts that an effective vaccine is available for horses and that most infected animals remain asymptomatic make the disease a lesser priority for animal health authorities. The examples described here can support other European countries wishing to strengthen their WNV surveillance or preparedness, and also serve as a model for surveillance and monitoring of other (vector-borne) zoonotic infections.

Vector prevalence and detection of Crimean-Congo haemorrhagic fever virus in Golestan Province, Iran.

BACKGROUND & OBJECTIVES: Crimean-Congo haemorrhagic fever virus (CCHFV) causes severe disease with fatality rate of 30%. The virus is transmitted to humans through the bite of an infected tick, direct contact with the products of infected livestock as well as nosocomially. The disease occurs sporadically throughout many of African, Asian and European countries. Different species of ticks serve either as vector or reservoir for CCHFV. This study was aimed to determine the prevalence of CCHFV in hard ticks (Ixodidae) in the Golestan Province of Iran. METHODS: A molecular survey was conducted on hard ticks (Ixodidae) isolated from six counties in Golestan Province, north of Iran during 2014-15. The ticks were identified using morphological characteristics and presence of CCHFV RNA was detected using RT-PCR. RESULTS: Data revealed the presence of CCHFV in 5.3% of the ticks selected for screening. The infected ticks belonged to Hyalomma dromedarii, Hy. anatolicum, Hy. marginatum and Rhipicephalus sanguineus species. INTERPRETATION & CONCLUSION: The study demonstrated that Hyalomma ticks are the main vectors of CCHFV in Golestan Province. Thus, preventive strategies such as using acaricides and repellents in order to avoid contact with Hyalomma ticks are proposed.

Taxonomy of the order Mononegavirales: update 2016.

In 2016, the order Mononegavirales was emended through the addition of two new families (Mymonaviridae and Sunviridae), the elevation of the paramyxoviral subfamily Pneumovirinae to family status (Pneumoviridae), the addition of five free-floating genera (Anphevirus, Arlivirus, Chengtivirus, Crustavirus, and Wastrivirus), and several other changes at the genus and species levels. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Close relationship between West Nile virus from Turkey and lineage 1 strain from Central African Republic.

We sequenced West Nile viruses (WNVs) from Turkey and found close relationships to WNV lineage 1 strain ArB310/67 from the Central African Republic, distinct from other WNVs circulating in the Mediterranean Basin, eastern Europe, and the Middle East. These findings suggest independent introductions of WNV strains from Africa to the Middle East.

Taxonomic reorganization of the family Bornaviridae.

Knowledge of bornaviruses has expanded considerably during the last decade. A possible reservoir of mammalian Borna disease virus has been identified, divergent bornaviruses have been detected in birds and reptiles, and endogenous bornavirus-like elements have been discovered in the genomes of vertebrates of several species. Previous sequence comparisons and alignments have indicated that the members of the current family Bornaviridae are phylogenetically diverse and are not adequately classified in the existing bornavirus taxonomy supported by the International Committee on Taxonomy of Viruses (ICTV). We provide an update of these analyses and describe their implications for taxonomy. We propose retaining the family name Bornaviridae and the genus Bornavirus but reorganizing species classification. PAirwise Sequence Comparison (PASC) of bornavirus genomes and Basic Local Alignment Search Tool (BLAST) comparison of genomic and protein sequences, in combination with other already published phylogenetic analyses and known biological characteristics of bornaviruses, indicate that this genus should include at least five species: Mammalian 1 bornavirus (classical Borna disease virus and divergent Borna disease virus isolate No/98), Psittaciform 1 bornavirus (avian/psittacine bornaviruses 1, 2, 3, 4, 7), Passeriform 1 bornavirus (avian/canary bornaviruses C1, C2, C3, LS), Passeriform 2 bornavirus (estrildid finch bornavirus EF), and Waterbird 1 bornavirus (avian bornavirus 062CG). This classification is also in line with biological characteristics of these viruses and their vertebrate hosts. A snake bornavirus, proposed to be named Loveridge's garter snake virus 1, should be classified as a member of an additional species (Elapid 1 bornavirus), unassigned to a genus, in the family Bornaviridae. Avian bornaviruses 5, 6, MALL, and another "reptile bornavirus" ("Gaboon viper virus") should stay unclassified until further information becomes available. Finally, we propose new virus names and abbreviations when necessary to achieve clear differentiation and unique identification.

Putative new West Nile virus lineage in Uranotaenia unguiculata mosquitoes, Austria, 2013.

West Nile virus (WNV) is becoming more widespread and markedly effecting public health. We sequenced the complete polyprotein gene of a divergent WNV strain newly detected in a pool of Uranotaenia unguiculata mosquitoes in Austria. Phylogenetic analyses suggest that the new strain constitutes a ninth WNV lineage or a sublineage of WNV lineage 4.