Biology subjects

Nissimov, J. I.

Publications and source records attributed to Nissimov, J. I..

10 recordsLinked to original sources

bioRxiv2026

Gas-vacuolate Microcystis evolves cyanophage resistance under low nitrogen conditions

Cyanophages can influence the dynamics of toxic cyanobacterial blooms. However, cyanobacteria can become resistant to viruses through natural selection processes. Here, we investigate the acquisition of virus resistance in a toxic, freshwater, gas-vacuolate, bloom-forming cyanobacterium, Microcystis aeruginosa, under different nutrient concentrations. We find that gas-vacuolate M. aeruginosa subpopulations acquire virus resistance in low nitrogen cultures regardless of their phosphorus concentration, whereas non-vacuolate subpopulations do not. After resequencing susceptible and resistant M. aeruginosa variants, we identify a mutation in the transmembrane domain of a nitrogen-related transporter as the most likely genetic cause of the resistance. Infection experiments further reveal a larger viral burst size and higher phycocyanin content in gas-vacuolate cells compared to non-vacuolate ones. Based on these experimental results, we propose an ecological model in which lower nitrogen concentrations, higher light intensities and increased virus-host contact rates facilitate the evolution of virus resistance in upper lake layers during Microcystis-dominated blooms.

microbiology↗

bioRxiv2025

A jumbo cyanophage encodes the most complete ribosomal protein set in the known virosphere

Viruses encode ribosomal proteins (RPs), but their genomes usually harbor a single RP-coding gene. Here, we reannotate the genome of the jumbo cyanophage PhiMa05 and show that it encodes six RPs, an RP acetyltransferase, and a ribosome biogenesis protein. Evolutionary analyses suggest that these viral RP-coding genes may have been horizontally transferred to certain members of the Vampirovibrionia, a non-photosynthetic basal lineage of Cyanobacteriota, via integration of the viral genome.

microbiology↗

bioRxiv2025

A Genome Sequence Variant Monitoring Program for Seasonal Influenza A H3N2 and Respiratory Syncytial Virus A using Wastewater-Based Surveillance in Ontario, Canada

Seasonal respiratory viruses, such as the Influenza A virus and the respiratory syncytial virus, are responsible for over a billion infections worldwide each year resulting in a substantial burden on health care systems. Surveillance of these viruses, including their prevalence in communities and their evolution, are essential for informing public health decisions and recommending vaccine formulations and schedules. Typically, these viruses are monitored using clinical samples from patients seeking medical attention. Recently, wastewater-based surveillance (WBS) has been leveraged to understand transmission dynamics and genome evolution of SARS-CoV-2 and seasonal respiratory viruses. To further the utility of WBS we developed and implemented novel tiled-amplicon sequencing assays to identify and track Influenza A virus H3N2 and respiratory syncytial virus A circulating in Southern Ontario, Canada. We also developed virus specific deconvolution tools to estimate the abundance of mixed lineages in wastewater. These assays were able to accurately determine which lineages were circulating in wastewater with high sensitivity and specificity. If implemented in regular surveillance programs, they could be used to inform real-time public health decisions and determine potential disease surge with impact on emergency room visits and hospitalization, as well as track which emerging strains will become predominant in the future and determine which strains should be the focus of seasonal vaccines.

genomics↗

bioRxiv2025

Hybrid sequencing reveals the genome of a Chrysochromulina parva virus and highlight its distinct replication strategy

Chrysochromulina parva (C. parva) is a eukaryotic freshwater haptophyte algae found in lakes and rivers worldwide. It is known to be infected by viruses, yet knowledge of the diversity and activity of these viruses is still very limited. Based on sequences of PCR-amplified polB gene fragments, Chrysochromulina parva virus BQ1 (CpV-BQ1) was the first known lytic agent of C. parva, and was considered a member of the virus family Phycodnaviridae, order Algavirales. However, the genome of a different C. parva-infecting virus (CpV-BQ2, or Tethysvirus ontarioense) from another virus family, the Mesomimiviridae, order Imitervirales, was the first sequenced. Here, we report the complete genome sequence of the putative phycodnavirus CpV-BQ1, accession PQ783904. The complete CpV-BQ1 genome sequence is 165,454 bp with a GC content of 32.32% and it encodes 193 open reading frames. Phylogenetic analyses of several virus hallmark genes including the DNA polymerase (polB), the late gene transcription factor (VLTF-3), and the putative A32-like virion packaging ATPase (Viral A32) all demonstrate that CpV-BQ1 is most closely related to other viruses in the phylum Megaviricetes within the order Algavirales, family Phycodnaviridae.

genomics↗

bioRxiv2024

AlphaFold 3 proteomic modelling reveals multiple photosystem structural homologs in freshwater cyanophages

Accurate protein structure prediction followed by structural homology detection enable the functional annotation of large numbers of otherwise obscure viral protein-coding genes. Here we employ AlphaFold 3 modeling and DALI structural homology search to predict the structures and functions of all 219 cryptic open reading frames in two representative freshwater cyanophages. We discover 28 previously unknown structural homologs, including three putative PsaD proteins in the same cyanophage, several viral structural proteins, and (to our knowledge) the first reported virus-encoded cyanobacteriochrome (DALI Z-score > 4.2 in all cases). Our results suggest that photosystem proteins may be more widespread in freshwater cyanophages than previously thought and emphasize the importance of applying structural homology detection methods when annotating viral genomes.

bioinformatics↗

bioRxiv2024

Structural models predict a significantly higher binding affinity between the NblA protein of cyanophage Ma-LMM01 and the phycocyanin of Microcystis aeruginosa NIES-298 compared to the host homolog

Horizontal gene transfer events between viruses and hosts are widespread across the virosphere. In cyanophage-host systems, such events often involve the transfer of genes involved in photosynthetic processes. The genome of the lytic cyanomyovirus Ma-LMM01 infecting the toxic, bloom-forming, freshwater Microcystis aeruginosa NIES-298 contains a homolog of the non-bleaching A (nblA) gene, which was probably acquired from its host. The function of the NblA protein is to disassemble phycobilisomes, cyanobacterial light harvesting complexes that can comprise up to half of the cellular soluble protein content. NblA thus plays an essential dual role in cyanobacteria: it protects the cell from high light intensities and increases the intracellular nitrogen pool under nutrient limitation. NblA has previously been shown to interact with phycocyanin, one of the main components of phycobilisomes. Using structural modeling and protein-protein docking, we show that the NblA dimer of Ma-LMM01 is predicted to have a significantly higher binding affinity for M. aeruginosa NIES-298 phycocyanin ({beta})6 hexamers, compared to the host homolog. Protein-protein docking suggests that the viral NblA structural model is able to bind deeper into the phycocyanin groove. The main structural difference between the virus and host NblA appears to be an additional -helix near the N-terminus of the viral NblA, which could be partly responsible for the deeper binding into phycocyanin. This unique helical region, absent in the cellular NblA, would be expected to constitute a viral evolutionary innovation. We propose that a higher binding affinity of NblA to the host phycocyanin may represent a selective advantage for the virus, whose rapid infection cycle requires an increased phycobilisome degradation rate that is not fulfilled by the NblA of the host.

microbiology↗

bioRxiv2023

Tracking SARS-CoV-2 variants of concern in wastewater: an assessment of nine computational tools using simulated genomic data

Wastewater-based surveillance (WBS) is an important epidemiological and public health tool for tracking pathogens across the scale of a building, neighbourhood, city, or region. WBS gained widespread adoption globally during the SARS-CoV-2 pandemic for estimating community infection levels by qPCR. Sequencing pathogen genes or genomes from wastewater adds information about pathogen genetic diversity which can be used to identify viral lineages (including variants of concern) that are circulating in a local population. Capturing the genetic diversity by WBS sequencing is not trivial, as wastewater samples often contain a diverse mixture of viral lineages with real mutations and sequencing errors, which must be deconvoluted computationally from short sequencing reads. In this study we assess nine different computational tools that have recently been developed to address this challenge. We simulated 100 wastewater sequence samples consisting of SARS-CoV-2 BA.1, BA.2, and Delta lineages, in various mixtures, as well as a Delta-Omicron recombinant and a synthetic "novel" lineage. Most tools performed well in identifying the true lineages present and estimating their relative abundances, and were generally robust to variation in sequencing depth and read length. While many tools identified lineages present down to 1% frequency, results were more reliable above a 5% threshold. The presence of an unknown synthetic lineage, which represents an unclassified SARS-CoV-2 lineage, increases the error in relative abundance estimates of other lineages, but the magnitude of this effect was small for most tools. The tools also varied in how they labelled novel synthetic lineages and recombinants. While our simulated dataset represents just one of many possible use cases for these methods, we hope it helps users understand potential sources of noise or bias in wastewater sequencing data and to appreciate the commonalities and differences across methods.

bioinformatics↗

bioRxiv2023

A Novel Tiled-Amplicon Sequencing Assay Targeting the Tomato Brown Rugose Fruit Virus (ToBRFV) Genome Reveals Widespread Distribution in Municipal Wastewater Treatment Systems in the Province of Ontario, Canada

Tomato Brown Rugose Fruit Virus (ToBRFV) is a plant pathogen that infects important Solanaceae crop species and can dramatically reduce tomato crop yields. The ToBRFV has rapidly spread around the globe due to its ability to escape detection by antiviral host genes, most notably Tm-22, which are used to confer resistance to other Tobamoviruses in tomato plants. Development of robust and reproducible methods for detecting viruses in the environment aids in the tracking and reduction of pathogen transmission. We detected ToBRFV in municipal wastewater influent (WWI) samples, likely due to its presence in human waste, demonstrating a widespread distribution of ToBRFV in WWI throughout Ontario, Canada. To aid in global ToBRFV surveillance efforts, we developed a tiled-amplicon approach to sequence and track the evolution of ToBRFV genomes in municipal WWI. Our assay recovers 97.5% of the 6393 bp ToBRFV RefSeq genome, omitting the terminal 5 and 3 ends. We demonstrate that our sequencing assay is a robust, sensitive, and highly specific method for recovering ToBRFV genomes. Our ToBRFV assay was developed using existing ARTIC Network resources, which includes genome specific primer design, sequencing library prep, and read analysis. Additionally, we adapted our lineage abundance estimation tool, Alcov, to estimate the abundance of ToBRFV clades in samples.

microbiology↗

bioRxiv2023

The curious case of cyanobacteria: a tale of light and darkness

Toxic algal bloom-forming cyanobacteria are a persistent problem globally for many aquatic environments. Their occurrence is attributed to eutrophication and rising temperatures due to climate change. The result of these blooms is often loss in biodiversity, economic impacts on tourism and fisheries, and risks to human and animal health. Of particular concern is the poorly understood interplay between viruses and toxic species that form blooms because viruses may exacerbate their harmful effects. Concurrently, cyanobacteria are also a source of bioactive compounds other than toxins, which makes them good candidates for drug discovery. We show that virus infection of the cyanobacterium Microcystis aeruginosa, results in as high as a 40-fold increase in the toxin microcystin two days post virus infection (dpi), and predict that microcystin levels may remain high in a body of water up to 7 dpi, long after water discoloration and cell lysis. This implicates viruses as major contributors to toxin release from cyanobacteria and emphasizes the importance of taking them into account in predictive models and in the assessment of water safety. We also show that bioactive compounds of M. aeruginosa inhibit and delay infection of single stranded DNA and single stranded RNA viruses. This highlights the potential of cyanobacteria as an excellent source for the discovery of novel antiviral compounds, and the ease with which screening for cyanobacterial antivirals can be achieved.

microbiology↗

bioRxiv2023

B12-dependent virioplankton demonstrate interseasonal dynamics and associate with a diversity of pelagic bacterioplankton

Through infection and lysis of their coexisting bacterial hosts, viruses impact the biogeochemical cycles sustaining globally significant pelagic oceanic ecosystems. Currently, little is known of the ecological interactions between lytic viruses and their bacterial hosts underlying these biogeochemical impacts at ecosystem scales. This study focused on populations of lytic viruses carrying the B12- dependent Class II monomeric ribonucleotide reductase (RNR) gene, ribonucleotide triphosphate reductase (RTPR), documenting seasonal changes in pelagic virioplankton and bacterioplankton using amplicon sequences of RTPR and the 16S rRNA gene, respectively. Amplicon sequence libraries were analyzed using compositional data analysis tools that account for the compositional nature of these data. Both virio- and bacterioplankton communities responded to environmental changes typically seen across seasonal cycles as well as shorter term upwelling-downwelling events. Defining RTPR-carrying viral populations according to major phylogenetic clades proved a more robust means of exploring virioplankton ecology than operational taxonomic units defined by percent sequence homology. Virioplankton RTPR populations showed positive associations with a broad phylogenetic diversity of bacterioplankton including dominant taxa within pelagic oceanic ecosystems such as Prochlorococcus and SAR11. Temporal changes in RTPR-virioplankton, occurring as both free viruses and within infected cells, indicated possible viral-host pairs undergoing sustained infection and lysis cycles throughout the seasonal study. Phylogenetic relationships inferred from RTPR sequences mirrored ecological patterns in virio- and bacterioplankton populations demonstrating possible genome to phenome associations for an essential viral replication gene.

ecology↗