Biology subjects

Matveev, E.

Publications and source records attributed to Matveev, E..

4 recordsLinked to original sources

bioRxiv2025

Comment on "Inverted repeats in the monkeypox virus genome are hot spots for mutation"

Recent work proposed that APOBEC-signature mutations in monkeypox virus (MPXV) are enriched in cruci-form structures formed by inverted repeats. We independently reanalyzed the same dataset with the published settings and several complementary approaches and found no statistically supported enrichment of mutations in these structures. While a modest trend at TC motif at 3 end of hairpin loop contexts cannot be excluded, current evidence is insufficient. Additional data and careful handling of overlapping structures are needed to clarify any association.

microbiology↗

bioRxiv2025

Analysis of MPXV RNA-seq Data Reveals Lack of Evidence of APOBEC3-mediated RNA Editing

The 2022 outbreak of monkeypox virus (MPXV), a double-stranded DNA virus, is remarkable for an unusually high number of single-nucleotide substitutions compared to earlier strains, with a strong bias toward C[->]T and G[->]A transitions consistent with the APOBEC3 cytidine deaminase activity. While APOBEC3-induced mutagenesis is well documented at the DNA level, its potential impact on MPXV RNA transcripts remains unclear. To assess whether APOBEC3 enzymes act on MPXV RNA, we analyzed RNA-seq data from infected samples. The enrichment of APOBEC-signature substitutions among high-frequency mismatched positions led us to consider two possibilities: RNA editing at hotspots or fixed DNA mutations. Multiple lines of evidence support the conclusion that these substitutions arise from DNA-level mutagenesis rather than RNA editing. These include a substantial number of G[->]A substitutions remaining after normalization by gene strand direction, a largely neutral impact of substitutions on protein-coding sequences, the lack of positional correlation with transcriptional features or RNA secondary structure typically associated with APOBEC action hotspots, and an overlap with known genomic mutations in MPXV strains. Analysis of the nucleotide context of observed substitutions indicated that APOBEC3A or APOBEC3B were likely drivers of DNA-level mutagenesis. ImportanceThe 2022 monkeypox virus (MPXV) outbreak showed an unusually high number of mutations thought to result from human antiviral enzymes of the APOBEC3 family. While such mutations have been clearly documented in the viral DNA, whether APOBEC3 also edits viral messenger RNA molecules remained unclear. In this study, we analyzed multiple publicly available MPXV RNA sequencing datasets to address this question. We found that the apparent APOBEC-like changes in RNA are best explained by fixed DNA mutations rather than active RNA editing. This finding helps clarify how MPXV evolves and adapts, suggesting that APOBEC3s role in shaping the virus likely operates at the DNA level. Understanding where and how these mutations occur provides insight into the viruss interaction with the human immune system and informs future studies on viral evolution and antiviral defenses.

microbiology↗

bioRxiv2020

Tissue-specific delivery system via AFF-1-coated pseudotyped Vesicular Stomatitis Virus in C. elegans

A hallmark of muscle development is that myoblasts fuse to form myofibers. However, smooth muscles and cardiomyocytes do not generally fuse. In C. elegans, the body wall muscles (BWMs), the physiological equivalents of skeletal muscles, are mononuclear. Here, to determine what would be the consequences of fusing BWMs, we express the cell-cell fusogen EFF-1 in these cells. We find that EFF-1 induces paralysis and dumpy phenotypes. To determine whether EFF-1-induced muscle fusion results in these pathologies we injected viruses pseudotyped with AFF-1, a paralog of EFF-1, into the pseudocoelom of C. elegans. When these engineered viruses encounter cells expressing EFF-1 or AFF-1 they are able to infect them as revealed by GFP expression from the viral genome. We find that AFF-1 viruses can fuse to EFF-1-expressing muscles revealing multinucleated fibers that cause paralysis and abnormal muscle morphogenesis. Thus, aberrant fusion of otherwise non-syncytial muscle cells may lead to pathological conditions. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=138 SRC="FIGDIR/small/099622v2_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@ebdf7dorg.highwire.dtl.DTLVardef@19d9246org.highwire.dtl.DTLVardef@1ee3698org.highwire.dtl.DTLVardef@425a0c_HPS_FORMAT_FIGEXP M_FIG C_FIG Significance statementMost cells are individual units that do not mix their cytoplasms. However, some cells fuse to become multinucleated in placenta, bones and muscles. In most animals, muscles are formed by myofibers that originate by cell-cell fusion. In contrast, in C. elegans the body wall muscles are mononucleated cells that mediate worm-like movement. EFF-1 and AFF-1 fusogens mediate physiological cell fusion in C. elegans. By ectopically expressing EFF-1 in body wall muscles we induce their fusion resulting in behavioral and morphological deleterious effects, revealing possible causes of congenital myopathies in humans. Using AFF-1-coated pseudoviruses we infect EFF-1-expressing muscle cells retargeting viral infection into these cells. We suggest that virus retargeting can be utilized to study myogenesis, neuronal regeneration, gamete fusion and screens for new fusogens in different organisms. In addition, our virus retargeting system can be used in gene-therapy, viral-based oncolysis and to study viral-host interactions.

cell biology↗

bioRxiv2016

Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

Cell-cell fusion is inherent to any form of sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in different organisms but their exact role is unclear. Here we show that Arabidopsis HAP2/GCS1 expression in mammalian cells is sufficient to promote cell-cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus and on the target cells results in HAP2-dependent virus-cell fusion. This bilateral requirement can be bypassed by replacing the plant gene with C. elegans EFF-1 somatic cell fusogen in one of the fusing cells or the virus, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and class II fusion proteins from enveloped viruses (e.g. dengue and Zika viruses). We name this superfamily FUSEXINS: FUSion proteins essential for sexual reproduction and EXoplasmic merger of plasma membranes. Thus, Fusexins unify the origin and evolution of sexual reproduction, enveloped virus entry into cells and somatic cell fusion.

cell biology↗