Natural history of eukaryotic DNA viruses with double jelly-roll major capsid proteins.

The phylum Preplasmiviricota (kingdom Bamfordvirae, realm Varidnaviria) is a broad assemblage of diverse viruses with comparatively short double-stranded DNA genomes (<50 kbp) that produce icosahedral capsids built from double jelly-roll major capsid proteins. Preplasmiviricots infect hosts from all cellular domains, testifying to their ancient origin and, in particular, are associated with six of the seven supergroups of eukaryotes. Preplasmiviricots comprise four major groups of viruses, namely, polintons, polinton-like viruses (PLVs), virophages, and adenovirids. We employed protein structure modeling and analysis to show that protein-primed DNA polymerases (pPolBs) of polintons, virophages, and cytoplasmic linear plasmids encompass an N-terminal domain homologous to the terminal proteins (TPs) of prokaryotic PRD1-like tectivirids and eukaryotic adenovirids that are involved in protein-primed replication initiation, followed by a viral ovarian tumor-like cysteine deubiquitinylase (vOTU) domain. The vOTU domain is likely responsible for the cleavage of the TP from the large pPolB polypeptide and is inactivated in adenovirids, in which TP is a separate protein. Many PLVs and transpovirons encode a distinct derivative of polinton-like pPolB that retains the TP, vOTU and pPolB polymerization palm domains but lacks the exonuclease domain and instead contains a supefamily 1 helicase domain. Analysis of the presence/absence and inactivation of the vOTU domains, and replacement of pPolB with other DNA polymerases in eukaryotic preplasmiviricots enabled us to outline a complete scenario for their origin and evolution.

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.

ICTV Virus Taxonomy Profile: Nairoviridae 2024.

Nairoviridae is a family for negative-sense RNA viruses with genomes of about 17.2-21.1 kb. These viruses are maintained in and/or transmitted by arthropods among birds, reptiles and mammals. Norwaviruses and orthonairoviruses can cause febrile illness in humans. Several orthonairoviruses can infect mammals, causing mild, severe and sometimes, fatal diseases. Nairovirids produce enveloped virions containing two or three single-stranded RNA segments with open reading frames that encode a nucleoprotein (N), sometimes 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 Nairoviridae, which is available at www.ictv.global/report/nairoviridae.

Treatment of highly virulent mammarenavirus infections-status quo and future directions.

INTRODUCTION: Mammarenaviruses are negative-sense bisegmented enveloped RNA viruses that are endemic in Africa, the Americas, and Europe. Several are highly virulent, causing acute human diseases associated with high case fatality rates, and are considered to be significant with respect to public health impact or bioterrorism threat. AREAS COVERED: This review summarizes the status quo of treatment development, starting with drugs that are in advanced stages of evaluation in early clinical trials, followed by promising candidate medical countermeasures emerging from bench analyses and investigational animal research. EXPERT OPINION: Specific therapeutic treatments for diseases caused by mammarenaviruses remain limited to the off-label use of ribavirin and transfusion of convalescent sera. Progress in identifying novel candidate medical countermeasures against mammarenavirus infection has been slow in part because of the biosafety and biosecurity requirements. However, novel methodologies and tools have enabled increasingly efficient high-throughput molecular screens of regulatory-agency-approved small-molecule drugs and led to the identification of several compounds that could be repurposed for the treatment of infection with several mammarenaviruses. Unfortunately, most of them have not yet been evaluated in vivo. The most promising treatment under development is a monoclonal antibody cocktail that is protective against multiple lineages of the Lassa virus in nonhuman primate disease models.

Monkeypox virus genomic accordion strategies.

The 2023 monkeypox (mpox) epidemic was caused by a subclade IIb descendant of a monkeypox virus (MPXV) lineage traced back to Nigeria in 1971. Person-to-person transmission appears higher than for clade I or subclade IIa MPXV, possibly caused by genomic changes in subclade IIb MPXV. Key genomic changes could occur in the genome's low-complexity regions (LCRs), which are challenging to sequence and are often dismissed as uninformative. Here, using a combination of highly sensitive techniques, we determine a high-quality MPXV genome sequence of a representative of the current epidemic with LCRs resolved at unprecedented accuracy. This reveals significant variation in short tandem repeats within LCRs. We demonstrate that LCR entropy in the MPXV genome is significantly higher than that of single-nucleotide polymorphisms (SNPs) and that LCRs are not randomly distributed. In silico analyses indicate that expression, translation, stability, or function of MPXV orthologous poxvirus genes (OPGs), including OPG153, OPG204, and OPG208, could be affected in a manner consistent with the established "genomic accordion" evolutionary strategies of orthopoxviruses. We posit that genomic studies focusing on phenotypic MPXV differences should consider LCR variability.

Polyubiquitylated rice stripe virus NS3 translocates to the nucleus to promote cytosolic virus replication via miRNA-induced fibrillin 2 upregulation.

Viruses are encapsidated mobile genetic elements that rely on host cells for replication. Several cytoplasmic RNA viruses synthesize proteins and/or RNAs that translocate to infected cell nuclei. However, the underlying mechanisms and role(s) of cytoplasmic-nuclear trafficking are unclear. We demonstrate that infection of small brown planthoppers with rice stripe virus (RSV), a negarnaviricot RNA virus, results in K63-linked polyubiquitylation of RSV's nonstructural protein 3 (NS3) at residue K127 by the RING ubiquitin ligase (E3) LsRING. In turn, ubiquitylation leads to NS3 trafficking from the cytoplasm to the nucleus, where NS3 regulates primary miRNA pri-miR-92 processing through manipulation of the microprocessor complex, resulting in accumulation of upregulated miRNA lst-miR-92. We show that lst-miR-92 regulates the expression of fibrillin 2, an extracellular matrix protein, thereby increasing RSV loads. Our results highlight the manipulation of intranuclear, cytoplasmic, and extracellular components by an RNA virus to promote its own replication in an insect vector.

Isolation of Diverse Simian Arteriviruses Causing Hemorrhagic Disease.

Genetically diverse simian arteriviruses (simarteriviruses) naturally infect geographically and phylogenetically diverse monkeys, and cross-species transmission and emergence are of considerable concern. Characterization of most simarteriviruses beyond sequence analysis has not been possible because the viruses fail to propagate in the laboratory. We attempted to isolate 4 simarteriviruses, Kibale red colobus virus 1, Pebjah virus, simian hemorrhagic fever virus, and Southwest baboon virus 1, by inoculating an immortalized grivet cell line (known to replicate simian hemorrhagic fever virus), primary macaque cells, macrophages derived from macaque induced pluripotent stem cells, and mice engrafted with macaque CD34+-enriched hematopoietic stem cells. The combined effort resulted in successful virus isolation; however, no single approach was successful for all 4 simarteriviruses. We describe several approaches that might be used to isolate additional simarteriviruses for phenotypic characterization. Our results will expedite laboratory studies of simarteriviruses to elucidate virus-host interactions, assess zoonotic risk, and develop medical countermeasures.

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.

ICTV Virus Taxonomy Profile: Kolmioviridae 2024.

Kolmioviridae is a family for negative-sense RNA viruses with circular, viroid-like genomes of about 1.5-1.7 kb that are maintained in mammals, amphibians, birds, fish, insects and reptiles. Deltaviruses, for instance, can cause severe hepatitis in humans. Kolmiovirids encode delta antigen (DAg) and replicate using host-cell DNA-directed RNA polymerase II and ribozymes encoded in their genome and antigenome. They require evolutionary unrelated helper viruses to provide envelopes and incorporate helper virus proteins for infectious particle formation. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Kolmioviridae, which is available at ictv.global/report/kolmioviridae.

Megataxonomy and global ecology of the virosphere.

Nearly all organisms are hosts to multiple viruses that collectively appear to be the most abundant biological entities in the biosphere. With recent advances in metagenomics and metatranscriptomics, the known diversity of viruses substantially expanded. Comparative analysis of these viruses using advanced computational methods culminated in the reconstruction of the evolution of major groups of viruses and enabled the construction of a virus megataxonomy, which has been formally adopted by the International Committee on Taxonomy of Viruses. This comprehensive taxonomy consists of six virus realms, which are aspired to be monophyletic and assembled based on the conservation of hallmark proteins involved in capsid structure formation or genome replication. The viruses in different major taxa substantially differ in host range and accordingly in ecological niches. In this review article, we outline the latest developments in virus megataxonomy and the recent discoveries that will likely lead to reassessment of some major taxa, in particular, split of three of the current six realms into two or more independent realms. We then discuss the correspondence between virus taxonomy and the distribution of viruses among hosts and ecological niches, as well as the abundance of viruses versus cells in different habitats. The distribution of viruses across environments appears to be primarily determined by the host ranges, i.e. the virome is shaped by the composition of the biome in a given habitat, which itself is affected by abiotic factors.

Thalamic deep brain stimulation for tourette syndrome increases cortical beta activity.

BACKGROUND: Deep brain stimulation (DBS) of the thalamus can effectively reduce tics in severely affected patients with Tourette syndrome (TS). Its effect on cortical oscillatory activity is currently unknown. OBJECTIVE: We assessed whether DBS modulates beta activity at fronto-central electrodes. We explored concurrent EEG sources and probabilistic stimulation maps. METHODS: Resting state EEG of TS patients treated with thalamic DBS was recorded in repeated DBS-on and DBS-off states. A mixed linear model was employed for statistical evaluation. EEG sources were estimated with eLORETA. Thalamic probabilistic stimulation maps were obtained by assigning beta power difference scores (DBS-on minus DBS-off) to stimulation sites. RESULTS: We observed increased beta power in DBS-on compared to DBS-off states. Modulation of cortical beta activity was localized to the midcingulate cortex. Beta modulation was more pronounced when stimulating the thalamus posteriorly, peaking in the ventral posterior nucleus. CONCLUSION: Thalamic DBS in TS patients modulates beta frequency oscillations presumably important for sensorimotor function and relevant to TS pathophysiology.

Virome profiling of fig wasps (Ceratosolen spp.) reveals virus diversity spanning four realms.

We investigated the virome of agaonid fig wasps (Ceratosolen spp.) inside syconia ("fruits") of various Ficus trees fed upon by frugivores such as pteropodid bats in Sub-Saharan Africa. This virome includes representatives of viral families spanning four realms and includes near-complete genome sequences of three novel viruses and fragments of five additional potentially novel viruses evolutionarily associated with insects, fungi, plants, and vertebrates. Our study provides evidence that frugivorous animals are exposed to a plethora of viruses by coincidental consumption of fig wasps, which are obligate pollinators of figs worldwide.

Comparative analysis of radiomics and deep-learning algorithms for survival prediction in hepatocellular carcinoma.

To examine the comparative robustness of computed tomography (CT)-based conventional radiomics and deep-learning convolutional neural networks (CNN) to predict overall survival (OS) in HCC patients. Retrospectively, 114 HCC patients with pretherapeutic CT of the liver were randomized into a development (n = 85) and a validation (n = 29) cohort, including patients of all tumor stages and several applied therapies. In addition to clinical parameters, image annotations of the liver parenchyma and of tumor findings on CT were available. Cox-regression based on radiomics features and CNN models were established and combined with clinical parameters to predict OS. Model performance was assessed using the concordance index (C-index). Log-rank tests were used to test model-based patient stratification into high/low-risk groups. The clinical Cox-regression model achieved the best validation performance for OS (C-index [95% confidence interval (CI)] 0.74 [0.57-0.86]) with a significant difference between the risk groups (p = 0.03). In image analysis, the CNN models (lowest C-index [CI] 0.63 [0.39-0.83]; highest C-index [CI] 0.71 [0.49-0.88]) were superior to the corresponding radiomics models (lowest C-index [CI] 0.51 [0.30-0.73]; highest C-index [CI] 0.66 [0.48-0.79]). A significant risk stratification was not possible (p > 0.05). Under clinical conditions, CNN-algorithms demonstrate superior prognostic potential to predict OS in HCC patients compared to conventional radiomics approaches and could therefore provide important information in the clinical setting, especially when clinical data is limited.

Cardiac remodelling in non-alcoholic fatty liver disease in the general population.

BACKGROUND AND AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk for cardiovascular disease. Our study investigates the contribution of NAFLD to changes in cardiac structure and function in a general population. METHODS: One thousand ninety-six adults (49.3% female) from the Study of Health in Pomerania underwent magnetic resonance imaging including cardiac and liver imaging. The presence of NAFLD by proton density fat fraction was related to left cardiac structure and function. Results were adjusted for clinical confounders using multivariable linear regression model. RESULTS: The prevalence for NAFLD was 35.9%. In adjusted multivariable linear regression models, NAFLD was positively associated with higher left ventricular mass index (ß = 0.95; 95% confidence interval (CI): 0.45; 1.45), left ventricular concentricity (ß = 0.043; 95% CI: 0.031; 0.056), left ventricular end-diastolic wall thickness (ß = 0.29; 95% CI: 0.20; 0.38), left atrial end-diastolic volume index (ß = 0.67; 95% CI: 0.01; 1.32) and inversely associated with left ventricular end-diastolic volume index (ß = -0.78; 95% CI: -1.51; -0.05). When stratified by sex, we only found significant positive associations of NAFLD with left ventricular mass index, left atrial end-diastolic volume index, left ventricular cardiac output and an inverse association with global longitudinal strain in women. In contrast, men had an inverse association with left ventricular end-diastolic volume index and left ventricular stroke volume. Higher liver fat content was stronger associated with higher left ventricular mass index, left ventricular concentricity and left ventricular end-diastolic wall thickness. CONCLUSION: NAFLD is associated with cardiac remodelling in the general population showing sex specific patterns in cardiac structure and function.

Repeatability of computed tomography liver radiomic features in a nonhuman primate model of diet-induced steatosis.

Purpose: We describe a method to identify repeatable liver computed tomography (CT) radiomic features, suitable for detection of steatosis, in nonhuman primates. Criteria used for feature selection exclude nonrepeatable features and may be useful to improve the performance and robustness of radiomics-based predictive models. Approach: Six crab-eating macaques were equally assigned to two experimental groups, fed regular chow or an atherogenic diet. High-resolution CT images were acquired over several days for each macaque. First-order and second-order radiomic features were extracted from six regions in the liver parenchyma, either with or without liver-to-spleen intensity normalization from images reconstructed using either a standard (B-filter) or a bone-enhanced (D-filter) kernel. Intrasubject repeatability of each feature was assessed using a paired t-test for all scans and the minimum p-value was identified for each macaque. Repeatable features were defined as having a minimum p-value among all macaques above the significance level after Bonferroni's correction. Features showing a significant difference with respect to diet group were identified using a two-sample t-test. Results: A list of repeatable features was generated for each type of image. The largest number of repeatable features was achieved from spleen-normalized D-filtered images, which also produced the largest number of second-order radiomic features that were repeatable and different between diet groups. Conclusions: Repeatability depends on reconstruction kernel and normalization. Features were quantified and ranked based on their repeatability. Features to be excluded for more robust models were identified. Features that were repeatable but different between diet groups were also identified.

ICTV Virus Taxonomy Profile: Leishbuviridae 2023.

Leishbuviridae is a family of negative-sense RNA viruses with genomes of about 8.0 kb that have been found in protists. The leishbuvirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a glycoprotein (GP), 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 Leishbuviridae, which is available at ictv.global/report/leishbuviridae.

ICTV Virus Taxonomy Profile: Discoviridae 2023.

Discoviridae is a family of negative-sense RNA viruses with genomes of 6.2-9.7 kb that have been associated with fungi and stramenopiles. The discovirid genome consists of three monocistronic RNA segments with open reading frames (ORFs) that encode a nucleoprotein (NP), a nonstructural protein (Ns), 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 Discoviridae, which is available at ictv.global/report/discoviridae.

ICTV Virus Taxonomy Profile: Jingchuvirales 2023.

Jingchuvirales is an order of negative-sense RNA viruses with genomes of 9.1-15.3 kb that have been associated with arachnids, barnacles, crustaceans, insects, fish and reptiles in Africa, Asia, Australia, Europe, North America and South America. The jingchuviral genome has two to four open reading frames (ORFs) that encode a glycoprotein (GP), a nucleoprotein (NP), a large (L) protein containing an RNA-directed RNA polymerase (RdRP) domain, and/or proteins of unknown function. Viruses in the order are only known from their genome sequences. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the order Jingchuvirales and on the families Aliusviridae, Chuviridae, Crepuscuviridae, Myriaviridae and Natareviridae, which are available at ictv.global/report/jingchuvirales, ictv.global/report/aliusviridae, ictv.global/report/chuviridae, ictv.global/report/crepuscuviridae, ictv.global/report/myriaviridae and ictv.global/report/natareviridae, respectively.