Michael T. Wolfinger

University of Vienna | UniWien · Research Group Bioinformatics and Computational Biology (BCB)

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3 UTR of tick-borne, insect-specific and no-known-vect...

Superspreading events shaped the coronavirus disease 2019 (COVID-19) pandemic, and their rapid identification and containment are essential for disease control. Here, we provide a national-scale analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading during the first wave of infections in Austria, a country that play...

Recent experimental evidence revealed a thorough understanding of the involvement of functional RNA elements in the 3′ untranslated regions (UTRs) of flaviviruses with virus tropism. Comparative genomics and thermodynamic modeling allow for the prediction and functional characterization of homologous structures in phylogenetically related viruses....

The internal ribosome entry site (IRES) RNA of bovine viral diarrhoea virus (BVDV), an economically significant Pestivirus, is required for the cap-independent translation of viral genomic RNA. Thus, it is essential for viral replication and pathogenesis. We applied a combination of high-throughput biochemical RNA structure probing (SHAPE-MaP) and...

Tick-borne encephalitis virus (TBEV) is the aetiological agent of tick-borne encephalitis, an infectious disease of the central nervous system that is often associated with severe sequelae in humans. While TBEV is typically classified into three subtypes, recent evidence suggests a more varied range of TBEV subtypes and lineages that differ substan...

An efficient structural refinement technique for protein-RNA complexes is proposed based on a combination of AI-based modeling and flexible docking. Specifically, an enhanced sampling method called parallel cascade selection molecular dynamics (PaCS-MD) was extended to include flexible docking to construct protein-RNA complexes from those obtained...

Evolutionarily conserved RNAs in untranslated regions are key regulators of the viral life cycle. Exoribonuclease-resistant RNAs (xrRNAs) are particularly interesting examples of structurally conserved elements because they actively dysregulate the messenger RNA (mRNA) degradation machinery of host cells, thereby mediating viral pathogenicity. We r...

Numerous viruses utilize essential long-range RNA-RNA genome interactions, specifically flaviviruses. Using Japanese encephalitis virus (JEV) as a model system, we computationally predicted and then bio-physically validated and characterized its long-range RNA-RNA genomic interaction. Using multiple RNA computation assessment programs, we determine...

Evolutionarily conserved RNAs in untranslated regions are key regulators of the viral life cycle. Exoribonuclease-resistant RNAs (xrRNAs) are particularly interesting examples of structurally conserved elements because they actively dysregulate the messenger RNA (mRNA) degradation machinery of host cells, thereby mediating viral pathogenicity. We r...

Pathogen nomenclature systems are a key component of effective communication and collaboration for researchers and public health workers. Since February 2021, the Pango nomenclature for SARS-CoV-2 has been sustained by crowdsourced lineage proposals as new isolates were added to a growing global dataset. This approach to dynamic lineage designation...

We are recruiting a highly motivated PhD candidate to join our team and help us understand the intricate mechanisms of structured viral RNAs in Synthetic Biology. The research project will be in the field of Computational RNA Biology, focusing on the design of exoribonuclease-resistant RNAs (xrRNAs) and xrRNA riboswitches. It is part of the FWF/DFG...

VEEnext is an interactive resource to study the evolution and global spread of the Venezuelan equine encephalitis (VEE) serocomplex viruses within the Nextstrain platform. It features 165 virus isolates sampled between 1938 and 2017.

CHIKVnext is an interactive web resource to study the evolution and spread of Chikungunya virus (CHIKV), featuring almost 1400 whole genome CHIKV isolates sampled between 1953 and 2022. It is built on the #Nextstrain platform that makes phylogeny and phylogeographics easily accessible through an interactive web application.

Flaviviruses subvert the host RNA decay machinery to produce subgenomic flavivirus RNA (sfRNA), products of the 5’-3’ exoribonuclease XRN1/Pacman stalling on secondary RNA structures in the 3’ untranslated region (UTR) of the viral genome. The classical insect-specific flavivirus (cISF) Kamiti River virus (KRV) has a unique 1.2 kb long 3’ UTR, of w...

Presentation given at the 7th 'Computational Approaches to RNA Structure and Function' conference, Benasque, Spain on 12 August 2022

The Musashi (MSI) family of RNA-binding proteins, comprising the two homologs Musashi-1 (MSI1) and Musashi-2 (MSI2), typically regulates translation and is involved in cell proliferation and tumorigenesis. MSI proteins contain two ribonucleoprotein-like RNA-binding domains, RBD1 and RBD2, that bind single-stranded RNA motifs with a central UAG trin...

Machine learning (ML) and in particular deep learning techniques have gained popularity for predicting structures from biopolymer sequences. An interesting case is the prediction of RNA secondary structures, where well established biophysics based methods exist. The accuracy of these classical methods is limited due to lack of experimental paramete...

In Pseudomonas aeruginosa, the RNA chaperone Hfq and the catabolite repression protein Crc act in concert to regulate numerous genes during carbon catabolite repression (CCR). After alleviation of CCR, the RNA CrcZ sequesters Hfq/Crc, which leads to a rewiring of gene expression to ensure the consumption of less preferred carbon and nitrogen source...

Human Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on th...

Numerous viruses utilize essential long-range RNA-RNA genome interactions, specifically flaviviruses. Using Japanese encephalitis virus (JEV) as a model system, we computationally predicted and then biophysically validated and characterized its long-range RNA-RNA genomic interaction. Using multiple RNA computation assessment programs, we determine...

Tick-borne encephalitis virus (TBEV) is the etiological agent of tick-borne encephalitis, an infectious disease of the central nervous system that is often associated with severe sequelae in humans. While TBEV is typically classified into three subtypes, recent evidence suggests a more varied range of TBEV subtypes and lineages that differ substant...

Machine learning (ML) and in particular deep learning techniques have gained popularity for predicting structures from biopolymer sequences. An interesting case is the prediction of RNA secondary structures, where well established biophysics based methods exist. The accuracy of these classical methods is limited due to lack of experimental paramete...

Human Long Intergenic Noncoding RNA-p21 (LincRNA-p21) is a regulatory noncoding RNA that plays an important role in promoting apoptosis. LincRNA-p21 is also critical in down-regulating many p53 target genes through its interaction with a p53 repressive complex. The interaction between LincRNA-p21 and the repressive complex is likely dependent on th...

The ability of RNA to fold into intricate structures in 2D and 3D is exploited by viruses to mediate tropism. Therefore, a deep understanding of RNA structure formation is crucial for the emerging field of virus bioinformatics. The ViennaRNA Package comes with a rich portfolio of tools to analyze RNA folding and the traits that are associated with...

Changes in v0.1.2: Add 3'UTR elements found in different subtypes of tick-borne encephalitis virus

We provide a custom Nextstrain build to explore the molecular epidemiology of Tick-borne encephalitis virus, available at https://nextstrain.org/groups/ViennaRNA/TBEVnext/v1.0

The Internal Ribosome Entry Site (IRES) RNA of Bovine viral diarrhea virus (BVDV), an economically significant Pestivirus, is required for the cap-independent translation of viral genomic RNA. Thus, it is essential for viral replication and pathogenesis. We applied a combination of high-throughput biochemical RNA structure probing (SHAPE-MaP) and i...

Pseudomonas aeruginosa ( Pae ) is notorious for its high-level resistance toward clinically used antibiotics. In fact, Pae has rendered most antimicrobials ineffective, leaving polymyxins and aminoglycosides as last resort antibiotics. Although several resistance mechanisms of Pae are known toward these drugs, a profounder knowledge of hitherto uni...

Tick-borne flaviviruses (TBFVs) infect mammalian hosts through tick bites and can cause various serious illnesses, such as encephalitis and hemorrhagic fevers, both in humans and animals. Despite their importance to public health, there is limited epidemiological information on TBFV infection in Africa. Herein, we report that a novel flavivirus, Mp...

Chikungunya virus (CHIKV) is an emerging Alphavirus which causes millions of human infections every year. Outbreaks have been reported in Africa and Asia since the early 1950s, from three CHIKV lineages: West African, East Central South African, and Asian Urban. As new outbreaks occurred in the Americas, individual strains from the known lineages h...

Chikungunya virus (CHIKV) is an emerging Alphavirus which causes millions of human infections every year. Outbreaks have been reported in Africa and Asia since the early 1950s, from three CHIKV lineages: West African, East Central South African, and Asian Urban. As new outbreaks occurred in the Americas, individual strains from the known lineages h...

Chikungunya virus (CHIKV) is an emerging Alphavirus which causes millions of human infections every year. Outbreaks have been reported in Africa and Asia since the early 1950s, from three CHIKV lineages: West African, East Central South African, and Asian Urban. As new outbreaks occurred in the Americas, individual strains from the known lineages h...

Recent experimental evidence revealed a thorough understanding of the involvement of functional RNA elements in the 3’ untranslated regions (UTRs) of flaviviruses with virus tropism. Comparative genomics and thermodynamic modeling allow for the prediction and functional characterization of homologous structures in phylogenetically related viruses....

RNA molecules may be subject to independent selection pressures on sequence and structure. This can, in principle, lead to the preservation of structural features without maintaining the exact position on the conserved sequence. Consequently, structurally analogous base pairs are no longer formed by homologous bases, and homologous nucleotides do n...

Tick-borne flaviviruses (TBFVs) infect mammalian hosts through tick bites and can cause various serious illnesses, such as encephalitis and hemorrhagic fevers, both in humans and animals. Despite their importance to public health, there is limited epidemiological information on TBFV infection in Africa is limited. Herein, we report that a novel fla...

Chikungunya virus (CHIKV) is an emerging alphavirus, which causes millions of human infections every year. Being the etiological agent of Chikungunya fever, a febrile disease associated with severe arthralgia, CHIKV has probably been circulating in sylvatic transmission cycles for many centuries. Outbreaks have been reported in Africa and Asia sinc...

To monitor the arthropod-borne virus transmission in mosquitoes, we have attempted both to detect and isolate viruses from 3304 wild-caught female mosquitoes in the Livingstone (Southern Province) and Mongu (Western Province) regions in Zambia in 2017. A pan-flavivirus RT-PCR assay was performed to identify flavivirus genomes in total RNA extracted...

Superspreading events shape the COVID-19 pandemic. Here we provide a national-scale analysis of SARS-CoV-2 outbreaks in Austria, a country that played a major role for virus transmission across Europe and beyond. Capitalizing on a national epidemiological surveillance system, we performed deep whole-genome sequencing of virus isolates from 576 samp...

Carbapenems are often the antibiotics of choice to combat life threatening infections caused by the opportunistic human pathogen Pseudomonas aeruginosa. The outer membrane porins OprD and OpdP serve as entry ports for carbapenems. Here, we report that the RNA chaperone Hfq governs post-transcriptional regulation of the oprD and opdP genes in a dist...

RNA viruses cause millions of infections in humans and animals every year, thereby challenging health systems and economies globally. Large-scale outbreaks of emerging and re-emerging agents, such as Dengue, Zika, Chikungunya, and Ebola virus in human and African swine fever virus in animals have been reported over the last years. These outbreaks c...

In silico prediction of evolutionarily conserved RNA secondary structures in the upstream 500 nucleotides of Wuhan seafood market pneumonia virus (Wuhan-nCoV, GenBank MN908947.3, top) and severe acute respiratory syndrome virus (SARS, RefSeq NC_004718.3, bottom). The genomic regions shown here comprise the 5'UTR and the amino-terminal region of the...

Arthropod-borne RNA viruses (arboviruses) represent a global health threat, causing millions of human and animal infections every year. Recent outbreaks of emerging and re-emerging viruses have revealed new clinical manifestations, e.g., the accumulation of congenital microcephaly cases during the Zika virus epidemic in the Americas 2015-2016. Whil...

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the family Togaviridae, has recently emerged in the Americas from lineages from two continents: Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent patterns of emergence and the curr...

RNA molecules may experience independent selection pressures on their sequence and (secondary) structure. Structural features then may be preserved without maintaining their exact position along the sequence. In such cases, corresponding base pairs are no longer formed by homologous bases, leading to the incongruent evolutionary conservation of seq...

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the family Togaviridae, has recently emerged in the Americas from lineages from two continents, Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent patterns of emergence and the curr...

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the family Togaviridae, has recently emerged in the Americas from lineages from two continents, Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent patterns of emergence and the curr...

Chikungunya virus (CHIKV), a mosquito-borne alphavirus of the Togaviridae family, has recently emerged in the Americas from two originating continents, Asia and Africa. Historically, CHIKV circulated as at least four lineages worldwide with both enzootic and epidemic transmission cycles. To understand the recent re-emergence patterns, and the curre...

RNA molecules may experience independent selection pressures on their sequence and (secondary) structure. Structural features then may be preserved without maintaining their exact position along the sequence. In such cases, corresponding base pairs are no longer formed by homologous bases, leading to the incongruent evolutionary conservation of seq...

Zika virus (ZIKV) belongs to a class of neurotropic viruses that have the ability to cause congenital infection, which can result in microcephaly or fetal demise. Recently, the RNA-binding protein Musashi-1 (Msi1), which mediates the maintenance and self-renewal of stem cells and acts as a translational regulator, has been associated with promoting...

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3'UTR of tick-borne, insect-specific and no-known-vect...

Untranslated regions (UTRs) of flaviviruses contain a large number of RNA structural elements involved in mediating the viral life cycle, including cyclisation, replication, and encapsidation. Here we report on a comparative genomics approach to characterize evolutionarily conserved RNAs in the 3'UTR of tick-borne, insect-specific and no-known-vect...

Translation factor a/eIF5A is highly conserved in Eukarya and Archaea. The eukaryal eIF5A protein is required for transit of ribosomes across consecutive proline codons, whereas the function of the archaeal orthologue remains unknown. Here, we provide a first hint for an involvement of Sulfolobus solfataricus (Sso) aIF5A in translation. CRISPR-medi...

Arboviruses are a group of viruses transmitted by arthropods, mostly ticks, and mosquitoes. Among the members of this group are the families Togaviridae and Flaviviridae, (+)ssRNA viruses, such as Chikungunya, Dengue, and Zika. Multiple of these viruses have demonstrated their ability to cause neuropathology in humans. In Zika, a protein binding mo...

Purpose: Arboviruses are a group of viruses transmitted by arthropods, mostly ticks, and mosquitoes. Among the members of this group are the families Togaviridae and Flaviviridae, (+)ssRNA viruses, such as Chikungunya, Dengue, and Zika. Multiple of these viruses have demonstrated their ability to cause neuropathology in humans. In Zika, a protein b...

The opportunistic human pathogen Pseudomonas aeruginosa is responsible for ∼ 10% of hospital-acquired infections worldwide. It is notorious for its high level resistance toward many antibiotics, and the number of multi-drug resistant clinical isolates is steadily increasing. A better understanding of the molecular mechanisms underlying drug resista...

Zika virus (ZIKV) belongs to a class of neurotropic viruses that have the ability to cause congenital infection, which can result in microcephaly or fetal demise. Recently, the RNA-binding protein Musashi-1 (Msi1), which mediates the maintenance and self-renewal of stem cells and acts as a translational regulator, has been associated with promoting...

The telomerase RNA in yeasts is large, usually >1000 nt, and contains functional elements that have been extensively studied experimentally in several disparate species. Nevertheless, they are very difficult to detect by homology-based methods and so far have escaped annotation in the majority of the genomes of Saccharomycotina. This is a consequen...

Flaviviruses represent a global health threat and are responsible for millions of infections in humans every year. During the 2015-2017 outbreak of Zika virus (ZIKV) in the Americas accumulation of congenital microcephaly cases was observed, which has been associated with ZIKV infection. However, the underlying biological mechanisms remain elusive....

Emerging and re-emerging arthropod-borne viruses such as Japanese encephalitis (JEV), Dengue (DENV), Yellow fever (YFV), and Chikungunya (CHIKV) viruses are a growing global health threat. Zika virus (ZIKV) is a neurotropic flavivirus (FV) that can cause congenital infection, which can result in microcephaly and fetal demise. Recently, the translat...