Biology subjects

Hoffmann, M.

Publications and source records attributed to Hoffmann, M..

At least 55 records · Page 3Linked to original sources

bioRxiv2023

circRNA-sponging: a pipeline for extensive analysis of circRNA expression and their role in miRNA sponging

MotivationCircular RNAs (circRNAs) are long non-coding RNAs (lncRNAs) often associated with diseases and considered potential biomarkers for diagnosis and treatment. Among other functions, circRNAs have been shown to act as microRNA (miRNA) sponges, preventing the role of miRNAs that repress their targets. However, there is no pipeline to systematically assess the sponging potential of circRNAs. ResultsWe developed circRNA-sponging, a nextflow pipeline that (1) identifies circRNAs via backsplicing junctions detected in RNA-seq data, (2) quantifies their expression values in relation to their linear counterparts spliced from the same gene, (3) performs differential expression analysis, (4) identifies and quantifies miRNA expression from miRNA-sequencing (miRNA-seq) data, (5) predicts miRNA binding sites on circRNAs, (6) systematically investigates potential circRNA-miRNA sponging events, (7) creates a network of competing endogenous RNAs, and (8) identifies potential circRNA biomarkers. We showed the functionality of the circRNA-sponging pipeline using RNA sequencing data from brain tissues, where we identified two distinct types of circRNAs characterized by a specific ratio of the number of the binding site to the length of the transcript. The circRNA-sponging pipeline is the first end-to-end pipeline to identify circRNAs and their sponging systematically with raw total RNA-seq and miRNA-seq files, allowing us to better indicate the functional impact of circRNAs as a routine aspect in transcriptomic research. Availabilityhttps://github.com/biomedbigdata/circRNA-sponging Contactmarkus.daniel.hoffmann@tum.de; markus.list@tum.de Supplementary MaterialSupplementary data are available at Bioinformatic Advances online.

bioinformatics↗

bioRxiv2022

TMPRSS2 is essential for SARS-CoV-2 Beta and Omicron infection

The COVID-19 pandemic remains a global health threat and novel antiviral strategies are urgently needed. SARS-CoV-2 employs the cellular serine protease TMPRSS2 for entry into lung cells and TMPRSS2 inhibitors are being developed for COVID-19 therapy. However, the SARS-CoV-2 Omicron variant, which currently dominates the pandemic, prefers the endo/lysosomal cysteine protease cathepsin L over TMPRSS2 for cell entry, raising doubts whether TMPRSS2 inhibitors would be suitable for treatment of patients infected with the Omicron variant. Nevertheless, the contribution of TMPRSS2 to spread of SARS-CoV-2 in the infected host is largely unclear. Here, we show that loss of TMPRSS2 strongly reduced the replication of the Beta variant in nose, trachea and lung of C57BL mice and protected the animals from weight loss and disease. Infection of mice with the Omicron variant did not cause disease, as expected, but again TMPRSS2 was essential for efficient viral spread in the upper and lower respiratory tract. These results identify a key role of TMPRSS2 in SARS-CoV-2 Beta and Omicron infection and highlight TMPRSS2 as an attractive target for antiviral intervention.

immunology↗

bioRxiv2022

Long-term immune protection against SARS-CoV-2 escape variants upon a single vaccination with murine cytomegalovirus expressing the spike protein

Current vaccines against COVID-19 elicit immune responses that are overall strong but wane rapidly. As a consequence, the necessary booster shots have led to vaccine fatigue. Hence, vaccines that would provide lasting protection against COVID-19 are needed, but are still unavailable. Cytomegaloviruses (CMV) elicit lasting and uniquely strong immune responses. Used as vaccine vectors, they may be attractive tools that obviate the need for boosters. Therefore, we tested the murine CMV (MCMV) as a vaccine vector against COVID-19 in relevant preclinical models of immunization and challenge. We have previously developed a recombinant murine CMV (MCMV) vaccine vector expressing the spike protein of the ancestral SARS-CoV-2 (MCMVS). In this study, we show that the MCMVS elicits a robust and lasting protection in young and aged mice. Notably, S-specific humoral and cellular immunity was not only maintained but even increased over a period of at least 6 months. During that time, antibody avidity continuously increased and expanded in breadth, resulting in neutralization of genetically distant variants, like Omicron BA.1. A single dose of MCMVS conferred rapid virus clearance upon challenge. Moreover, MCMVS vaccination controlled two immune-evading variants of concern (VoCs), the Beta (B.1.135) and the Omicron (BA.1) variants. Thus, CMV vectors provide unique advantages over other vaccine technologies, eliciting broadly reactive and long-lasting immune responses against COVID-19. Authors SummaryWhile widespread vaccination has substantially reduced risks of severe COVID presentations and morbidity, immune waning and continuous immune escape of novel SARS-CoV-2 variants have resulted in a need for numerous vaccine boosters and a continuous adaptation of vaccines to new SARS-CoV-2 variants. We show in proof of principle experiments with a recombinant murine cytomegalovirus expressing the SARS-CoV-2 spike protein (MCMVS) that one immunization with a CMV vaccine vector drives enduring protection in both young and aged mice, with long-term maturation of immune responses that broaden the antiviral effects over time. Hence, this approach resolves issues of immune waning and mitigates the effects of COVID-19 evolution and immune escape, reducing the need for additional immunizations and potentially improving vaccine compliance.

immunology↗

bioRxiv2022

SARS-CoV-2 vaccination of laboratory rhesus monkeys (Macaca mulatta): Monitoring and efficacy

The availability of effective vaccines and a high vaccination rate allowed the recent mitigation, or even withdrawal, of many protective measures for containing the SARS CoV-2 pandemic. At the same time, new and highly mutated variants of the virus are found to have significantly higher transmissibility and reduced vaccine efficacy, thus causing high infection rates during the third year of the pandemic. The combination of reduced measures and increased infectivity poses a particular risk for unvaccinated individuals, including animals susceptible to the virus. Among the latter, non-human primates (NHPs) are particularly vulnerable. They serve as important models in various fields of biomedical research and because of their cognitive capabilities, they receive particular attention in animal welfare regulations around the world. Yet, although they played an extraordinarily important role for developing and testing vaccines against SARS-CoV-2, the protection of captive rhesus monkeys against Covid-19 has rarely been discussed. We here report upon twofold mRNA vaccination of a cohort of 19 rhesus monkeys (Macaca mulatta) against infection by SARS-CoV-2. All animals were closely monitored on possible side effects of vaccination, and were tested for neutralising antibodies against the virus. The data show that vaccination of rhesus monkeys is a safe and reliable measure to protect these animals against SARS-CoV-2.

immunology↗

bioRxiv2022

TF-Prioritizer: a java pipeline to prioritize condition-specific transcription factors

BackgroundEukaryotic gene expression is controlled by cis-regulatory elements (CREs), including promoters and enhancers, which are bound by transcription factors (TFs). Differential expression of TFs and their binding affinity at putative CREs determine tissue- and developmental-specific transcriptional activity. Consolidating genomic data sets can offer further insights into the accessibility of CREs, TF activity, and, thus, gene regulation. However, the integration and analysis of multi-modal data sets are hampered by considerable technical challenges. While methods for highlighting differential TF activity from combined chromatin state data (e.g., ChIP-seq, ATAC-seq, or DNase-seq) and RNA-seq data exist, they do not offer convenient usability, have limited support for large-scale data processing, and provide only minimal functionality for visually interpreting results. ResultsWe developed TF-Prioritizer, an automated pipeline that prioritizes condition-specific TFs from multi-modal data and generates an interactive web report. We demonstrated its potential by identifying known TFs along with their target genes, as well as previously unreported TFs active in lactating mouse mammary glands. Additionally, we studied a variety of ENCODE data sets for cell lines K562 and MCF-7, including twelve histone modification ChIP-seq as well as ATAC-seq and DNase-seq datasets, where we observe and discuss assay-specific differences. ConclusionTF-Prioritizer accepts ATAC-seq, DNase-seq, or ChIP-seq and RNA-seq data as input and identifies TFs with differential activity, thus offering an understanding of genome-wide gene regulation, potential pathogenesis, and therapeutic targets in biomedical research.

bioinformatics↗

bioRxiv2022

EDGE2: advancing the prioritisation of threatened evolutionary history for conservation action

The global biodiversity crisis threatens the natural world and its capacity to provide benefits to humans into the future. The conservation of evolutionary history, captured by the measure phylogenetic diversity (PD), is linked to the maintenance of these benefits and future options. The Evolutionarily Distinct and Globally Endangered (EDGE) metric has, since 2007, been used to identify species for conservation action that embody large amounts of threatened evolutionary history. In 2017, we convened a workshop to update the EDGE metric to incorporate advances in the field of phylogenetically-informed conservation. Building on that workshop, we devised the metric EDGE2, which we present here. EDGE2 uses a modular, tiered approach to provide priority rankings--and associated measures of uncertainty in both phylogenetic and extinction risk data--for all species in a clade. EDGE2 takes into account the extinction risk of closely-related species to better reflect the contribution a species is expected to make to overall PD in the future. We applied EDGE2 to the worlds mammals to identify an updated list of priority EDGE species and compare the results with the original EDGE approach. Despite similarity in the priority lists produced between EDGE and EDGE2, EDGE2 places greater priority on species with fewer close relatives on the Tree of Life. As we approach a crossroads for global biodiversity policy, EDGE2 exemplifies how academic and applied conservation biologists can collaborate to guide effective priority-setting to conserve the most irreplaceable components of biodiversity upon which humanity depends.

zoology↗

bioRxiv2022

Brain-wide imaging of an adult vertebrate with image transfer oblique plane microscopy

Optical imaging is a powerful tool to visualise and measure neuronal activity. However, due to the size and opacity of vertebrate brains it has until now been impossible to simultaneously image neuronal circuits at cellular resolution across the entire adult brain. This is true even for the smallest known vertebrate brain in the teleost Danionella, which is still too large for existing volumetric imaging approaches. Here we introduce image transfer oblique plane microscopy, which uses a new optical refocusing solution via a custom fibre-optical faceplate, enabling a large field-of-view of up to 4 mm3 at a volume rate of 1 Hz. We demonstrate the power of this method with the first brain-wide recording of neuronal activity in an adult vertebrate.

neuroscience↗

bioRxiv2022

Selectively expressed RNA molecules: a new dimension infunctionalized cell targeting

Exact targeting of specific mammalian cell types or diseased cells is one of the most urgently needed prerequisites for a new generation of potent pharmaceuticals. Different approaches have been pursued, failing mainly due to a lack of specific surface markers in most cases. Developing a completely novel RNA-based methodology, we can now ensure exact cell targeting and simultaneously combine this with selective expression of effector proteins, thereby functionalization of the target cell for therapy, diagnostics or cell steering. The specific combination of the molecular properties of antisense technology and mRNA therapy with functional RNA secondary structures allowed us to develop selectively expressed RNA molecules for medical applications. These so-called seRNAs remain inactive in non-target cells and are only activated by partial degradation to induce translation in preselected cell types of interest. Cell type specificity and type of functionalization are easily adaptable based on a simple modular system. In proof of concept in vitro and in vivo studies we used seRNAs as a highly selective platform technology for powerful glioblastoma cancer cell targeting and significantly reduce brain tumors of mice without detectable side effects with just a single treatment within days. Our data open up new potential avenues for the efficient treatment of various cancers and other human diseases.

cell biology↗

bioRxiv2022

spongEffects: ceRNA modules offer patient-specific insights into the miRNA regulatory landscape

MotivationCancer is one of the leading causes of death worldwide. Despite significant improvements in prevention and treatment, mortality remains high for many cancer types. Hence, innovative methods that use molecular data to stratify patients and identify biomarkers are needed. Promising biomarkers can also be inferred from competing endogenous RNA (ceRNA) networks that capture the gene-miRNA gene regulatory landscape. Thus far, the role of these biomarkers could only be studied globally but not in a sample-specific manner. To mitigate this, we introduce spongEffects, a novel method that infers subnetworks (or modules) from ceRNA networks and calculates patient- or sample-specific scores related to their regulatory activity. ResultsWe show how spongEffects can be used for downstream interpretation and machine learning tasks such as tumor classification and for identifying subtype-specific regulatory interactions. In a concrete example of breast cancer subtype classification, we prioritize modules impacting the biology of the different subtypes. In summary, spongEffects prioritizes ceRNA modules as biomarkers and offers insights into the miRNA regulatory landscape. Notably, these module scores can be inferred from gene expression data alone and can thus be applied to cohorts where miRNA expression information is lacking. Availabilityhttps://bioconductor.org/packages/devel/bioc/html/SPONGE.html Contactmarkus.daniel.hoffmann@tum.de; markus.list@tum.de Supplementary informationSupplementary data are available at Bioinformatics online.

systems biology↗

bioRxiv2022

SARS-CoV-2 neutralizing camelid heavy-chain-only antibodies as powerful tools for diagnostic and therapeutic applications

IntroductionThe ongoing COVID-19 pandemic situation caused by SARS-CoV-2 and variants of concern such as B.1.617.2 (Delta) and recently, B.1.1.529 (Omicron) is posing multiple challenges to humanity. The rapid evolution of the virus requires adaptation of diagnostic and therapeutic applications. ObjectivesIn this study, we describe camelid heavy-chain-only antibodies (hcAb) as useful for novel in vitro diagnostic assays and for therapeutic applications due to their neutralizing capacity. MethodsFive antibody candidates were selected out of a naive camelid library by phage display and expressed as full-length IgG2 antibodies. The antibodies were characterized by Western blot, enzyme-linked immunosorbent assays, surface plasmon resonance with regard to their specificity to the recombinant SARS-CoV-2 Spike protein and to SARS-CoV-2 virus-like particles. Neutralization assays were performed with authentic SARS-CoV-2 and pseudotyped viruses (wildtype and Omicron). ResultsAll antibodies efficiently detect recombinant SARS-CoV-2 Spike protein and SARS-CoV-2 virus-like particles in different ELISA setups. The best combination was shown with hcAb B10 as catcher antibody and HRP-conjugated hcAb A7.2 as the detection antibody. Further, four out of five antibodies potently neutralized authentic wildtype SARS-CoV-2 and particles pseudotyped with the SARS-CoV-2 Spike proteins of the wildtype and Omicron variant, sublineage BA.1 at concentrations between 0.1 and 0.35 ng/mL (ND50). ConclusionCollectively, we report novel camelid hcAbs suitable for diagnostics and potential therapy. Graphical Abstract O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

immunology↗

bioRxiv2022

LanA (Language Atlas): A probabilistic atlas for the language network based on fMRI data from >800 individuals

Two analytic traditions characterize fMRI language research. One relies on averaging activations voxel-wise across individuals. This approach has limitations: because of inter-individual variability in the locations of language areas, a location in a common brain space cannot be meaningfully linked to function. An alternative approach relies on identifying language areas in each individual using a functional localizer. Because of its greater sensitivity, functional resolution, and interpretability, functional localization is gaining popularity, but it is not always feasible, and cannot be applied retroactively to past studies. We provide a solution for bridging these currently disjoint approaches in the form of a probabilistic functional atlas created from fMRI data for an extensively validated language localizer in 806 individuals. This atlas enables estimating the probability that any given location in a common brain space belongs to the language network, and thus can help interpret group-level peaks and meta-analyses of such peaks, and lesion locations in patient investigations. More meaningful comparisons of findings across studies should increase robustness and replicability in language research.

neuroscience↗

bioRxiv2022

Musical expertise shapes visual-melodic memory integration

Music can act as a powerful mnemonic device that can elicit vivid episodic memories. However, how musical information is integrated with non-musical information is largely unknown. Here, we investigated whether and how musical expertise modulates binding of melodies and visual information into integrated memory representations. We reasoned that the significant mnemonic demands of musicianship might alter the underlying integration process and reveal mechanisms by which music promotes retrieval of non-musical memories. Professional musicians and musical laypersons learned overlapping pairs of everyday objects and melodies (AB- and BC-pairs, object-melody and melody-object pairs). Participants were then tested for memory of studied pairs (direct trials) and for inferential AC-decisions (indirect trials). Although musicians showed a higher overall performance than non-musicians, both groups performed well above chance level in both trial types. Non-musicians reacted faster in indirect compared to direct trials, whereas the reverse pattern was found in musicians. Differential correlations of trial type performance between groups further suggested that non-musicians efficiently formed integrated ABC-triplets already during the encoding phase of the task, while musicians separately memorized AB- and BC-pairs and recombined them at retrieval for AC-decisions. Our results suggest that integrative encoding is a default mechanism for integration of musical and non-musical stimuli that works with great efficacy even in musically untrained subjects and may contribute to the everyday experience of music-evoked episodic memories. By contrast, recombination at retrieval seems to be an advanced strategy for memory integration that critically depends on an expert ability to maintain and discriminate musical stimuli across extended memory delays.

neuroscience↗

bioRxiv2022

Assessing the global impact of targeted conservation actions on species abundance

In recent years, vertebrate population abundance has declined at unprecedented rates (WWF 2020). In response, targeted conservation measures - such as breeding programs or species-specific habitat management - have been applied to halt population declines, aid population recovery, and reduce and reverse the loss of biodiversity (Salafsky et al. 2008; Bolam et al. 2020). Until now, assessments of conservation actions have focused on the extent to which they reduce extinction risk, impact populations within protected areas, or increase the global area of land under protection (Hoffmann et al. 2010, 2015; Barnes et al. 2016; Maxwell et al. 2020; Bolam et al. 2020; Grace et al. 2021a). Here, we record and analyze conservation actions for 26,904 vertebrate populations from 4,629 species, to measure the impact of targeted conservation on vertebrate abundance. Using a counterfactual approach to represent population trends in the absence of conservation, we demonstrate that targeted actions have delivered substantial positive effects on the abundance of recipient vertebrate populations worldwide. We show that, in the absence of conservation, a global indicator of vertebrate abundance would have declined even more. Positive population trends were associated with vertebrate populations subject to species or habitat management. We demonstrate that targeted conservation actions can help to reverse global biodiversity loss and show the value of counterfactual analysis for impact evaluation - an important step towards reversing biodiversity declines.

ecology↗

bioRxiv2021

The Omicron variant is highly resistant against antibody-mediated neutralization - implications for control of the COVID-19 pandemic

The rapid spread of the SARS-CoV-2 Omicron variant suggests that the virus might become globally dominant. Further, the high number of mutations in the viral spike-protein raised concerns that the virus might evade antibodies induced by infection or vaccination. Here, we report that the Omicron spike was resistant against most therapeutic antibodies but remained susceptible to inhibition by Sotrovimab. Similarly, the Omicron spike evaded neutralization by antibodies from convalescent or BNT162b2-vaccinated individuals with 10- to 44-fold higher efficiency than the spike of the Delta variant. Neutralization of the Omicron spike by antibodies induced upon heterologous ChAdOx1/BNT162b2-vaccination or vaccination with three doses of BNT162b2 was more efficient, but the Omicron spike still evaded neutralization more efficiently than the Delta spike. These findings indicate that most therapeutic antibodies will be ineffective against the Omicron variant and that double immunization with BNT162b2 might not adequately protect against severe disease induced by this variant.

microbiology↗

bioRxiv2021

LRRC15 mediates an accessory interaction with the SARS-CoV-2 spike protein

The interactions between severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) and human host factors enable the virus to propagate infections that lead to COVID-19. The spike protein is the largest structural component of the virus and mediates interactions essential for infection, including with the primary ACE2 receptor. We performed two independent cell-based systematic screens to determine whether there are additional proteins by which the spike protein of SARS-CoV-2 can interact with human cells. We discovered that in addition to ACE2, expression of LRRC15 also causes spike protein binding. This interaction is distinct from other known spike attachment mechanisms such as heparan sulfates or lectin receptors. Measurements of orthologous coronavirus spike proteins implied the interaction was restricted to SARS-CoV-2, suggesting LRRC15 represents a novel class of spike binding interaction. We localized the interaction to the C-terminus of the S1 domain, and showed that LRRC15 shares recognition of the ACE2 receptor binding domain. From analyzing proteomics and single-cell transcriptomics, we identify LRRC15 expression as being common in human lung vasculature cells and fibroblasts. Although infection assays demonstrated that LRRC15 alone is not sufficient to permit viral entry, we present evidence it can modulate infection of human cells. This unexpected interaction merits further investigation to determine how SARS-CoV-2 exploits host LRRC15 and whether it could account for any of the distinctive features of COVID-19. In briefWe present evidence from genome-wide screening that the spike protein of SARS-CoV-2 interacts with human cells expressing LRRC15. The interaction is distinct from previously known classes of spike attachment factors, and appears to have emerged recently within the coronavirus family. Although not sufficient for cell invasion, this interaction can modulate viral infection. Our data point to an unappreciated host factor for SARS-CoV-2, with potential relevance to COVID-19. Highlights- Two systematic cell-based screens for SARS-CoV-2 spike protein binding identify LRRC15 as a human host factor - Interaction with LRRC15 is reproducible in different human cell lines and independent of known glycan or ACE2 binding pathways - The C-terminal S1 domain of SARS-CoV-2 spike binds LRRC15 with sub-micromolar affinity, while related coronavirus spikes do not - LRRC15 is expressed in tissues with high ACE2 levels and may modulate infection

biochemistry↗

bioRxiv2021

Interferon induction and not replication interference mainly determines anti-influenza virus activity of defective interfering particles

Defective interfering (DI) RNAs arise during influenza virus replication, can be packaged into particles (DIPs) and suppress spread of wildtype (WT) virus. However, the molecular signatures of DI RNAs and the mechanism underlying antiviral activity are incompletely understood. Here, we show that any central deletion is sufficient to convert a viral RNA into a DI RNA and that antiviral activity of DIPs is inversely correlated with DI RNA length when induction of the interferon (IFN) system is disfavored. When induction of the IFN system was allowed, it was found to be the major contributor to DIP antiviral activity. Finally, while both DIPs and influenza virus triggered expression of IFN-stimulated genes (ISG) only virus stimulated robust expression of IFN. These results suggest a key role of innate immune activation in DIP antiviral activity and point towards previously unappreciated differences in DIP- and influenza virus-mediated activation of the effector functions of the IFN system. ImportanceDefective interfering (DI) RNAs naturally arise during RNA virus infection. They can be packaged into defective interfering particles (DIPs) and exert antiviral activity by suppressing viral genome replication and inducing the interferon (IFN) system. However, inhibition of influenza virus infection by DI RNAs has been incompletely understood. Here, we show that induction of the IFN system and not suppression of genome replication is the major determinant of DIP antiviral activity. Moreover, we demonstrate that DIPs induce IFN-stimulated genes (ISG) but not IFN with high efficiency. Our results reveal unexpected major differences in influenza virus and DIP activation of the IFN system, a key barrier against viral infection, and provide insights into how to design DIPs for antiviral therapy.

molecular biology↗

bioRxiv2021

Protective mucosal immunity against SARS-CoV-2 after heterologous systemic RNA-mucosal adenoviral vector immunization

Several effective SARS-CoV-2 vaccines are currently in use, but in the light of waning immunity and the emergence of novel variants, effective boost modalities are needed in order to maintain or even increase immunity. Here we report that intranasal vaccinations with adenovirus 5 and 19a vectored vaccines following a systemic DNA or mRNA priming result in strong systemic and mucosal immunity in mice. In contrast to two intramuscular injections with an mRNA vaccine, the mucosal boost with adenoviral vectors induced high levels of IgA and tissue-resident memory T cells in the respiratory tract. Mucosal neutralization of virus variants of concern was also enhanced by the intranasal boosts. Importantly, priming with mRNA provoked a more comprehensive T cell response consisting of circulating and tissue-resident memory T cells after the boost, while a DNA priming induced mostly mucosal T cells. Concomitantly, the intranasal boost strategies provided protection against symptomatic disease. Therefore, a mucosal booster immunization after mRNA priming is a promising approach to establish mucosal immunity in addition to systemic responses.

immunology↗

bioRxiv2021

Increased lung cell entry of B.1.617.2 and evasion of antibodies induced by infection and BNT162b2 vaccination

The delta variant of SARS-CoV-2, B.1.617.2, emerged in India and has subsequently spread to over 80 countries. B.1.617.2 rapidly replaced B.1.1.7 as the dominant virus in the United Kingdom, resulting in a steep increase in new infections, and a similar development is expected for other countries. Effective countermeasures require information on susceptibility of B.1.617.2 to control by antibodies elicited by vaccines and used for COVID-19 therapy. We show, using pseudotyping, that B.1.617.2 evades control by antibodies induced upon infection and BNT162b2 vaccination, although with lower efficiency as compared to B.1.351. Further, we found that B.1.617.2 is resistant against Bamlanivimab, a monoclonal antibody with emergency use authorization for COVID-19 therapy. Finally, we show increased Calu-3-lung cell entry and enhanced cell-to-cell fusion of B.1.617.2, which may contribute to augmented transmissibility and pathogenicity of this variant. These results identify B.1.617.2 as an immune evasion variant with increased capacity to enter and fuse lung cells.

molecular biology↗