ICTV Virus Taxonomy Profile: Filoviridae 2024.

Filoviridae is a family of negative-sense RNA viruses with genomes of about 13.1-20.9 kb that infect fish, mammals and reptiles. The filovirid genome is a linear, non-segmented RNA with five canonical open reading frames (ORFs) that encode a nucleoprotein (NP), a polymerase cofactor (VP35), a glycoprotein (GP1,2), a transcriptional activator (VP30) and a large protein (L) containing an RNA-directed RNA polymerase (RdRP) domain. All filovirid genomes encode additional proteins that vary among genera. Several filovirids (e.g., Ebola virus, Marburg virus) are pathogenic for humans and highly virulent. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Filoviridae, which is available at www.ictv.global/report/filoviridae.

Renaming of genera Ebolavirus and Marburgvirus to Orthoebolavirus and Orthomarburgvirus, respectively, and introduction of binomial species names within family Filoviridae.

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group continues to prospectively refine the established nomenclature for taxa included in family Filoviridae in an effort to decrease confusion of genus, species, and virus names and to adhere to amended stipulations of the International Code of Virus Classification and Nomenclature (ICVCN). Recently, the genus names Ebolavirus and Marburgvirus were changed to Orthoebolavirus and Orthomarburgvirus, respectively. Additionally, all established species names in family Filoviridae now adhere to the ICTV-mandated binomial format. Virus names remain unchanged and valid. Here, we outline the revised taxonomy of family Filoviridae as approved by the ICTV in April 2023.

Development of Oncolytic Vectors Based on Human Adenovirus Type 6 for Cancer Treatment.

Human Adenovirus type 6 (HAdV-C6) is a promising candidate for the development of oncolytic vectors as it has low seroprevalence and the intrinsic ability to evade tissue macrophages. However, its further development as a therapeutic agent is hampered by the lack of convenient cloning methods. We have developed a novel technology when a shuttle plasmid carrying the distal genome parts with modified E1A and E3 regions is recombined in vitro with the truncated HAdV-C6 genome. Using this approach, we have constructed a novel Ad6-hT-GM vector controlled by the hTERT promoter and expressing granulocyte-macrophage colony-stimulating factor (GM-CSF) instead of 6.7K and gp19K E3 proteins. We have demonstrated that control by the hTERT promoter may result in delayed viral replication, which nevertheless does not significantly change the cytotoxic ability of recombinant viruses. The insertion of the transgene by displacing the E3-6.7K/gp19K region does not drastically change the expression patterns of E3 genes; however, mild changes in expression from major late promoter were observed. Finally, we have demonstrated that the treatment of human breast cancer xenografts in murine models with Ad6-hT-GM significantly decreased the tumor volume and improved survival time compared to mock-treated mice.

Genetic Diversity and Possible Origins of the Hepatitis B Virus in Siberian Natives.

A total of 381 hepatitis B virus (HBV) DNA sequences collected from nine groups of Siberian native populations were phylogenetically analyzed along with 179 HBV strains sampled in different urban populations of former western USSR republics and 50 strains from Central Asian republics and Mongolia. Different HBV subgenotypes predominated in various native Siberian populations. Subgenotype D1 was dominant in Altaian Kazakhs (100%), Tuvans (100%), and Teleuts (100%) of southern Siberia as well as in Dolgans and Nganasans (69%), who inhabit the polar Taimyr Peninsula. D2 was the most prevalent subgenotype in the combined group of Nenets, Komi, and Khants of the northern Yamalo-Nenets Autonomous Region (71%) and in Yakuts (36%) from northeastern Siberia. D3 was the main subgenotype in South Altaians (76%) and Buryats (40%) of southeastern Siberia, and in Chukchi (51%) of the Russian Far East. Subgenotype C2 was found in Taimyr (19%) and Chukchi (27%), while subgenotype A2 was common in Yakuts (33%). In contrast, D2 was dominant (56%) in urban populations of the former western USSR, and D1 (62%) in Central Asian republics and Mongolia. Statistical analysis demonstrated that the studied groups are epidemiologically isolated from each other and might have contracted HBV from different sources during the settlement of Siberia.

Adenovirus Type 6: Subtle Structural Distinctions from Adenovirus Type 5 Result in Essential Differences in Properties and Perspectives for Gene Therapy.

Adenovirus vectors are the most frequently used agents for gene therapy, including oncolytic therapy and vaccine development. It's hard to overestimate the value of adenoviruses during the COVID-19 pandemic as to date four out of four approved viral vector-based SARS-CoV-2 vaccines are developed on adenovirus platform. The vast majority of adenoviral vectors are based on the most studied human adenovirus type 5 (HAdV-C5), however, its immunogenicity often hampers the clinical translation of HAdV-C5 vectors. The search of less seroprevalent adenovirus types led to another species C adenovirus, Adenovirus type 6 (HAdV-C6). HAdV-C6 possesses high oncolytic efficacy against multiple cancer types and remarkable ability to induce the immune response towards carrying antigens. Being genetically very close to HAdV-C5, HAdV-C6 differs from HAdV-C5 in structure of the most abundant capsid protein, hexon. This leads to the ability of HAdV-C6 to evade the uptake by Kupffer cells as well as to distinct opsonization by immunoglobulins and other blood proteins, influencing the overall biodistribution of HAdV-C6 after systemic administration. This review describes the structural features of HAdV-C6, its interaction with liver cells and blood factors, summarizes the previous experiences using HAdV-C6, and provides the rationale behind the use of HAdV-C6 for vaccine and anticancer drugs developments.

Oncolytic Effect of Adenoviruses Serotypes 5 and 6 Against U87 Glioblastoma Cancer Stem Cells.

BACKGROUND/AIM: Oncolytic adenoviruses are promising therapeutic agents against both the bulk of tumor cells and cancer stem cells. The present study intended to test the oncolytic capability of adenovirus serotype 6 (Ad6), which has a lower seroprevalence and hepatotoxicity relatively to adenovirus 5 (Ad5), against the glioblastoma and its cancer stem cells. MATERIALS AND METHODS: Oncolytic efficacy of Ad6 was compared to widespread Ad5 both in vitro and in vivo, using the U87 and U251 human glioblastoma cell lines and subcutaneously transplanted U87 cells in SCID mice, respectively. RESULTS: Ad6 had a dose-dependent cytotoxicity toward glioblastoma cells in vitro and its intratumoral injections lead to a significant (p<0.05) decrease in volume of U87 xenografts, similarly to Ad5. Based on the innate capability of glioblastoma cancer stem cells to internalize a fluorescent-labeled double-stranded DNA probe, the spatial localization of these cells was estimated and it was shown that the number of cancer stem cells tended to decrease under adenovirus therapy as compared to the control group. CONCLUSION: Ad6 was shown to be a promising agent for treating glioblastomas.

Features of monocyte-derived dendritic cells encompassing a rare subpopulation of cells that are capable of natural internalization of extracellular dsDNA.

The present study demonstrates that monocyte-derived dendritic cells (moDCs) produced in vitro using a GM-CSF and IFN-α differentiation protocol encompass a rare (∼5%) subpopulation of cells showing classical dendritic cell morphology and capable of natural internalization of extracellular self-DNA. We established that DEFB, HMGB1, LL-37 and RAGE antigens, which mediate the process of DNA internalization, are expressed on the surface of moDCs similar to plasmacytoid dendritic cells. However, in constrast to the latter subpopulation, these cells do not produce interleukin (IL)-37. Nonetheless, the process of DNA internalization was not in direct relation to the presence of the above antigens on the surface of these cells. Dendritic cells were sorted into total and non-DNA-internalizing populations and cytokine production was analyzed at 24-48 hours post-DNA treatment. We show that massive secretion of cytokines by dendritic cells is associated with the dsDNA-internalizing subpopulation. A total pool of IFN-moDCs secrete pro-inflammatory "first-wave" cytokines (IL-2, IL-6, IL-8, TNF-α) at both 24 and 48 hours time points. The anti-inflammatory cytokines IL-4 and IL-10 were found to be modestly induced, whereas GM-CSF, G-CSF, and IFN-γ production was strongly induced. Treatment of moDCs with dsDNA results in the up-regulated transcription of IFN-α, IFN-ß, IFN-γ, IL-8, IL-10, and VEGF by 6 hours. Combined dsDNA + chloroquine treatment has a synergistic effect on transcription of only one of the genes tested, with the pro-inflammatory cytokine IFN-ß displaying the strongest fold induction by 24 hours.

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).

Identification of the xenograft and its ascendant sphere-forming cell line as belonging to EBV-induced lymphoma, and characterization of the status of sphere-forming cells.

BACKGROUND: We have characterized the human cell line arised from the Epstein-Barr virus (EBV) positive multiple myeloma aspirate subjected to the long-term cultivation. This cell line has acquired the ability to form free-floating spheres and to produce a xenograft upon transplantation into NOD/SCID mice. METHODS: Cells from both in vitro culture and developed xenografts were investigated with a number of analytical approaches, including pathomorphological analysis, FISH analysis, and analysis of the surface antigens and of the VDJ locus rearrangement. RESULTS: The obtained results, as well as the confirmed presence of EBV, testify that both biological systems are derived from B-cells, which, in turn, is a progeny of the EBV-transformed B-cellular clone that supplanted the primordial multiple myeloma cells. Next we assessed whether cells that (i) were constantly present in vitro in the investigated cell line, (ii) were among the sphere-forming cells, and (iii) were capable of internalizing a fluorescent TAMRA-labeled DNA probe (TAMRA+ cells) belonged to one of the three types of undifferentiated bone marrow cells of a multiple myeloma patient: CD34+ hematopoietic stem cells, CD90+ mesenchymal stem cells, and clonotypic multiple myeloma cell. CONCLUSION: TAMRA+ cells were shown to constitute the fourth independent subpopulation of undifferentiated bone marrow cells of the multiple myeloma patient. We have demonstrated the formation of ectopic contacts between TAMRA+ cells and cells of other types in culture, in particular with CD90+ mesenchymal stem cells, followed by the transfer of some TAMRA+ cell material into the contacted cell.

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).

Bioselection of coxsackievirus B6 strain variants with altered tropism to human cancer cell lines.

Cancer cells develop increased sensitivity to members of many virus families and, in particular, can be efficiently infected and lysed by many low-pathogenic human enteroviruses. However, because of their great genetic heterogeneity, cancer cells display different levels of sensitivity to particular enterovirus strains, which may substantially limit the chances of a positive clinical response. We show that a non-pathogenic strain of coxsackievirus B6 (LEV15) can efficiently replicate to high titers in the malignant human cell lines C33A, DU145, AsPC-1 and SK-Mel28, although it displays much lower replication efficiency in A431 and A549 cells and very limited replication ability in RD and MCF7 cells, as well as in the normal lung fibroblast cell line MRC-5 and the immortalized mammary epithelial cell line MCF10A. By serial passaging in RD, MCF7 and A431 cells, we obtained LEV15 strain variants that had acquired high replication capacity in the appropriate carcinoma cell lines without losing their high replication capability in the original set of cancer cell lines and had limited replication capability in untransformed cells. The strains demonstrated improved oncolytic properties in nude-mouse xenografts. We identified nucleotide changes responsible for the phenotypes and suggest a bioselection approach for a generation of oncolytic virus strains with a wider spectrum of affected tumors.

Hepatitis C virus subtype 3a was introduced in the USSR in the early 1980s.

A total of 2120 nucleotide sequences of the NS5b region of HCV subtype 3a were analysed, including 310 strains derived from former republics of the USSR (Azerbaijan, Estonia, Lithuania, Russia, Tajikistan and Uzbekistan). Among the viral isolates collected from former regions of the Soviet Union, 294 strains formed 3 sustained phylogenetic clusters, with each having a common origin. Phylodynamic analysis demonstrated that the most recent common ancestors of the current strains inside the three clusters were introduced into the USSR population in 1981±1, 1984±2 and 1985±2, respectively (the confidence intervals were calculated using Student's t-distribution, P<0.05). The time estimation obtained for HCV subtype 3a correlated well with the historical and epidemiological context of this period, and in particular with the start of widespread injection drug use in the USSR in the first half of the 1980s.

Implementation of Objective PASC-Derived Taxon Demarcation Criteria for Official Classification of Filoviruses.

The mononegaviral family Filoviridae has eight members assigned to three genera and seven species. Until now, genus and species demarcation were based on arbitrarily chosen filovirus genome sequence divergence values (≈50% for genera, ≈30% for species) and arbitrarily chosen phenotypic virus or virion characteristics. Here we report filovirus genome sequence-based taxon demarcation criteria using the publicly accessible PAirwise Sequencing Comparison (PASC) tool of the US National Center for Biotechnology Information (Bethesda, MD, USA). Comparison of all available filovirus genomes in GenBank using PASC revealed optimal genus demarcation at the 55-58% sequence diversity threshold range for genera and at the 23-36% sequence diversity threshold range for species. Because these thresholds do not change the current official filovirus classification, these values are now implemented as filovirus taxon demarcation criteria that may solely be used for filovirus classification in case additional data are absent. A near-complete, coding-complete, or complete filovirus genome sequence will now be required to allow official classification of any novel "filovirus." Classification of filoviruses into existing taxa or determining the need for novel taxa is now straightforward and could even become automated using a presented algorithm/flowchart rooted in RefSeq (type) sequences.

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).

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.].

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).

First genetic characterization of rotavirus C in Russia.

Rotaviruses C (RVC) cause sporadic cases and outbreaks of diarrhea in humans and animals worldwide. The aim of this study was to monitor RVC during a surveillance study of sporadic cases of viral gastroenteritis in the Novosibirsk and Omsk regions of Russia from 2006 to 2011. A total of 2144 stool samples from children and adults hospitalized with acute gastroenteritis were tested for RVC by RT-PCR. Sixteen RVC-positive stool samples were detected at a rate of 0.6% (13/2037) in children and 2.8% (3/107) in adults. The low detection rate suggested that RVC infection was an uncommon cause of hospitalization in Russia. The complete VP7, VP4, VP6, and NSP4 gene sequences were determined. It was found that RVCs with at least two different genome backgrounds circulated in Siberia. VP4, VP6, and NSP4 gene sequences of most Russian RVC strains clustered with South Asian strains, while the VP7 gene showed a closer relationship to European strains. Meanwhile, only VP4 and NSP4 sequences of the strain Omsk08-386 clustered with South Asian strains, while its VP6 and VP7 sequences clustered with European strains. This is the first genetic characterization of Russian RVC strains and the first report on the prevalence of RVC in the Asian part of Russia.

Molecular epidemiology of noroviruses associated with sporadic gastroenteritis in children in Novosibirsk, Russia, 2003-2012.

Noroviruses (NoVs) are an important cause of acute gastroenteritis worldwide. To monitor the molecular epidemiology of NoVs genogroup II (GII) in Novosibirsk, Russia, a total of 10,198 stool samples from young children hospitalized with acute gastroenteritis and two asymptomatic comparison groups were collected from 2003 to 2012. All samples were screened for the presence of NoV GII, rotavirus, and astrovirus by RT-PCR. The prevalence of NoV in gastroenteritis cases was 13.1%, varying from 7.1% to 21.3% in different seasons. Rotavirus and/or astrovirus were detectable in 25% of the NoV-positive samples. NoV was detected throughout the year with a seasonal increase during winter months. Based on sequence analysis of regions D and/or C within the VP1 gene, 892 identified NoV strains were divided into nine genotypes­GII.3 (51%), GII.4 (44%), GII.6 (2%), as well as GII.1, GII.2, GII.5, GII.7, GII.16, and GII.21 (totally, 3%). The prevalence of NoV in the comparison groups was considerably lower (∼2.5%); only GII.4 (n = 6), GII.21 (n = 2) and GII.1 (n = 1) genotypes were revealed. Based on phylogenetic analysis of the ORF1/ORF2 junction region sequences, GII.P21/GII.3 recombinant and GII.P4/GII.4 were prevalent genotypes (totally, 93%) and their ratio changed every season. The median age of children with NoV infection was 6.6 months (range, <1-35 months), but it was different depending on NoV genotype. Children infected with the NoV GII.3 were younger (median 6.2 months) than GII.4-positive patients (median 9.1 months). This is the first long-term systematic study of NoV molecular epidemiology in Russia.

Filovirus RefSeq entries: evaluation and selection of filovirus type variants, type sequences, and names.

Sequence determination of complete or coding-complete genomes of viruses is becoming common practice for supporting the work of epidemiologists, ecologists, virologists, and taxonomists. Sequencing duration and costs are rapidly decreasing, sequencing hardware is under modification for use by non-experts, and software is constantly being improved to simplify sequence data management and analysis. Thus, analysis of virus disease outbreaks on the molecular level is now feasible, including characterization of the evolution of individual virus populations in single patients over time. The increasing accumulation of sequencing data creates a management problem for the curators of commonly used sequence databases and an entry retrieval problem for end users. Therefore, utilizing the data to their fullest potential will require setting nomenclature and annotation standards for virus isolates and associated genomic sequences. The National Center for Biotechnology Information's (NCBI's) RefSeq is a non-redundant, curated database for reference (or type) nucleotide sequence records that supplies source data to numerous other databases. Building on recently proposed templates for filovirus variant naming [ ()////-], we report consensus decisions from a majority of past and currently active filovirus experts on the eight filovirus type variants and isolates to be represented in RefSeq, their final designations, and their associated sequences.

Discussions and decisions of the 2012­2014 International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group, January 2012­June 2013.

The International Committee on Taxonomy of Viruses (ICTV) Filoviridae Study Group prepares proposals on the classification and nomenclature of filoviruses to reflect current knowledge or to correct disagreements with the International Code of Virus Classification and Nomenclature (ICVCN). In recent years, filovirus taxonomy has been corrected and updated, but parts of it remain controversial, and several topics remain to be debated. This article summarizes the decisions and discussion of the currently acting ICTV Filoviridae Study Group since its inauguration in January 2012.