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PubMed2026

Clinical and genomic characterization of Influenza A co-infection with SARS-CoV-2 and Influenza B: a respiratory surveillance study in Assam, India.

Influenza and SARS-CoV-2 are the primary contributors to seasonal respiratory infections and frequently co-circulate, creating significant health challenges. The present respiratory surveillance study was conducted in Dibrugarh, Assam, India from January 2025 to August 2025 to investigate the genomic characteristics of circulating viruses and identify potential co-infections. Overall, 4,948 respiratory samples were screened using multiplex real-time PCR, followed by subtyping of Influenza A and Influenza B. Next-generation sequencing (NGS) was performed in selected positives of SARS-CoV-2 and Influenza A. Genomic analysis included mutational profiling, phylogenetic analysis and N-glycosylation site prediction using bioinformatics tools. Two co-infection cases were detected: one involving Influenza A (H3N2) with SARS-CoV-2 (Omicron XFG lineage) and another involving Influenza A (H3N2) with Influenza B (Victoria lineage). Both patients experienced mild illness without hospitalisation. NGS revealed that the Influenza A (H3N2) viruses belonged to clade 3C.2a1b.2a.2a.3a.1 while SARS-CoV-2 sequence was classified under the Omicron XFG lineage. Mutational analysis of the HA gene showed several amino acid differences compared to the reference vaccine strain A/Darwin/6/2021. N-glycosylation analysis predicted conserved sites at positions 79, 181, 262, and 301 in all strains along with an additional predicted site at position 110 in both co-infection cases. Although the co-infection cases presented with mild clinical manifestations, the observed genomic variations indicate a potential role of co-infecting viruses in shaping viral evolution. Given the limited genomic data available from Northeast India, the study underscores the need for sustained large scale follow up and genomic surveillance to monitor emerging mutations and target future vaccine strategies.

Humans↗

PubMed2026

Wastewater-based sequencing of respiratory syncytial virus to investigate lineage dynamics and antigenic site mutations: a retrospective genomic epidemiology study.

BACKGROUND: Respiratory syncytial virus (RSV) infections pose a substantial health burden, particularly for clinically vulnerable populations such as infants and older adults. Although novel immunoprophylactic interventions show promise in providing protection, many countries may not have robust surveillance systems to monitor circulating RSV lineages and detect mutations that might reduce the effectiveness of these new interventions. We aimed to assess the diversity and temporal dynamics of circulating RSV lineages in urban populations through amplicon-based sequencing and analysis of wastewater extracts. METHODS: In this prospective observational wastewater-based genomic surveillance study, 32 raw influent 24-h composite samples were collected during the 2022-23 and 2023-24 RSV seasons from both Zurich and Geneva, Switzerland. We applied an RSV subtype-specific amplicon-based sequencing approach to obtain RSV-A and RSV-B sequences from all 64 samples. Mutations relative to reference genomes were identified at positions with read depth above 30. Relative abundances of RSV lineages were estimated from frequencies of lineage-signature mutations, present in greater than 90% of publicly available sequences of that lineage. FINDINGS: Relative abundances of RSV-B (2022-23) and RSV-A (2023-24) lineages were estimated over the two RSV seasons. During the 2022-23 season, the RSV-B B.D.E.1 lineage prevailed in both cities. In the 2023-24 season, multiple RSV-A lineages cocirculated, including A.D.1, A.D.3, A.D.5, and their sub-lineages. Identification and frequency estimation of mutations showed low-frequency, non-synonymous mutations in antigenic sites on the fusion gene of both RSV-A and RSV-B, some of which have not been reported in clinical sequences. The primary outcome was identification and relative abundance of RSV lineages in wastewater samples. INTERPRETATION: These findings show the potential of wastewater-based genomic surveillance to identify and track circulating RSV lineages and clinically relevant mutations. As novel RSV immunoprophylaxis measures are introduced in upcoming RSV seasons, wastewater-derived genomic RSV data provide a valuable baseline for understanding RSV diversity and future viral evolution under increased immunological pressure. FUNDING: This study was funded by the Swiss National Science Foundation and in part by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health. Funding for sample collection and processing was provided by the Swiss Federal Office of Public Health.

Humans↗

PubMed2026

Healthcare-facility-based SARS-CoV-2 genomic surveillance in Brazil: experience from the global action in healthcare network.

UNLABELLED: Genomic sequencing is essential to effectively monitor the SARS-CoV-2 evolution and spread of its lineages. Healthcare-facility-based SARS-CoV-2 genomic surveillance has been proposed as a valuable strategy, considering the characteristics of its target population. As part of the Centers for Disease Control and Prevention's Global Action in Healthcare Network program, this study aimed to describe the distribution and frequency of SARS-CoV-2 lineages in two tertiary-care hospitals in Brazil, where the genomic sequencing capacity is limited. Whole-genome sequencing of SARS-CoV-2 samples obtained from 993 healthcare workers (75.4%) and inpatients (24.6%) was analyzed between February 2023 and August 2024. In total, 113 distinct lineages were identified. Notably, we observed a temporal replacement of predominant lineages corresponding to three distinct epidemic waves: the first wave dominated by XBB.1.5 and XBB.2.3 (February 2023 to June 2023), the second by GK.1.1 and JD.1.1 (September 2023 to December 2023), and the third by JN.1 and JN.1.9 (January 2024 to April 2024). JN.1.9 was the only lineage with a significantly higher prevalence among healthcare workers compared to inpatients. Additionally, we identified cases of co-infection with genetically distinct variants, underscoring the potential for healthcare-based monitoring to capture events relevant to viral evolution. Overall, our findings were consistent with those observed across Brazil, suggesting that this strategy may be valuable for SARS-CoV-2 genomic surveillance. They also indicate a clear temporal pattern of lineage replacement, reflecting successive waves driven by emerging variants and rapid global dissemination. IMPORTANCE: Genomic surveillance of SARS-CoV-2 remains essential for identifying emerging variants with increased transmissibility, immune escape, or pathogenicity. While most genomic surveillance efforts focus on community-based sampling, a healthcare-facility-based strategy may offer a complementary approach. In this study, we describe SARS-CoV-2 lineage dynamics over an 18-month period among healthcare workers and hospitalized patients in southern Brazil. Our findings align closely with regional and national trends, supporting the value of healthcare-facility-based SARS-CoV-2 genomic surveillance for documenting the local genomic landscape and demonstrating the feasibility and value of this approach in settings with limited genome sequencing capacity. Additionally, this approach may be applicable to other respiratory viruses in healthcare settings; however, further studies would be needed to confirm this.

Humans↗

PubMed2024

Rapid spread of the SARS-CoV-2 Omicron XDR lineage derived from recombination between XBB and BA.2.86 subvariants circulating in Brazil in late 2023.

Recombination plays a crucial role in the evolution of SARS-CoV-2. The Omicron XBB* recombinant lineages are a noteworthy example, as they have been the dominant SARS-CoV-2 variant worldwide in the first half of 2023. Since November 2023, a new recombinant lineage between Omicron subvariants XBB and BA.2.86, designated XDR, has been detected mainly in Brazil. In this study, we reconstructed the spatiotemporal dynamics and estimated the absolute and relative transmissibility of the XDR lineage. The XDR lineage displayed a recombination breakpoint in the ORF1a-coding region, and the most closely related sequences to the 5' and 3' ends of the recombinant correspond to JD.1.1 and JN.1.1 lineages, respectively. The first XDR sequences were detected in November 2023 in the Northeastern Brazilian region, and their prevalence rapidly surged from <1% to 25% by February 2024. The Bayesian phylogeographic analysis supports that the XDR lineage likely emerged in the Northeastern Brazilian region around late October 2023 and rapidly disseminated within and outside Brazilian borders from mid-November onward. The median effective reproductive number of the XDR lineage in Brazil during the initial expansion phase was estimated to be around 1.5, and the average relative instantaneous reproduction numbers of XDR and JN* lineages were estimated to be 1.37 and 1.29 higher than that of co-circulating XBB* lineages. In summary, these findings support that the recombinant lineage XDR arose in the Northeastern Brazilian region in October 2023, shortly after the first detection of JN.1 sequences in the country. In Brazil, the XDR lineage exhibited a higher transmissibility level than its parental XBB.* lineages and is spreading at a rate similar to or slightly faster than the JN.1* lineages.IMPORTANCEThis study highlights the emergence and rapid dissemination of the recombinant SARS-CoV-2 XDR lineage, derived from the Omicron lineages JD.1.1 and JN.1.1. The XDR lineage exhibited equivalent transmissibility to its JN.1* parental lineages and quickly spread across Brazil in late 2023. The findings underscore the critical role of real-time genomic surveillance in detecting novel variants with higher transmission potential. By utilizing phylogenetic and epidemiological methods, this research provides important insights into the molecular dynamics of XDR, which could inform public health responses and vaccine composition updates. The study's significance lies in its ability to document the impact of recombination on viral evolution, offering valuable information to the field of virology and pandemic preparedness.

Brazil↗

PubMed2026

Tracking the shifting landscape of SARS-CoV-2 variants in Lebanon among healthcare workers and hospitalized patients.

UNLABELLED: Genomic surveillance of SARS-CoV-2 is critical for tracking viral evolution and informing public health responses. This study characterized variants circulating among healthcare workers (HCWs) and hospitalized patients in Lebanon between January 2022 and September 2024. A total of 530 SARS-CoV-2-positive nasopharyngeal swabs were collected from five Lebanese governorates and subjected to whole-genome sequencing. Correlations between variant circulation and a number of demographic and clinical variables were assessed. Most HCWs were female (64%), young adults (20-30 years, 39%), and had no comorbidities (97%). In contrast, hospitalized patients were mostly older adults (>60 years, 55.6%) with underlying conditions (77%). Early 2022 was marked by BA.1- and BA.2-like Omicron variants, followed by the predominance of BA.5-like lineages. In 2023, recombinant XBB sublineages became widespread. By 2024, these were largely replaced by next-generation variants, including JN.1 and KP.3.1.1. Despite differences in demographics and exposure risk, both groups showed parallel variant evolution. These findings reflect global and regional patterns and highlight the dynamic nature of SARS-CoV-2 circulation in Lebanon. IMPORTANCE: This study provides a comprehensive snapshot of SARS-CoV-2 variant evolution in Lebanon between 2022 and 2024, focusing on healthcare workers and hospitalized patients. By combining genomic and clinical data, it reveals how successive Omicron subvariants emerged and spread within key population groups. The detection of diverse and evolving lineages, including XBB recombinants and next-generation variants such as JN.1, underscores the ongoing antigenic drift of SARS-CoV-2. These insights reinforce the value of continued genomic surveillance for pandemic preparedness, especially in regions where data remain limited. Understanding local variant dynamics can guide targeted vaccination strategies and health policy decisions.

Humans↗

PubMed2026

Molecular Epidemiology of Human Metapneumovirus in Kilifi, Coastal Kenya, 2016-2017 and 2021-2024.

BACKGROUND: Human metapneumovirus (hMPV) is a major contributor of acute respiratory infections (ARI) in childhood and vulnerable adults. It comprises two antigenically distinct lineages (A and B), with multiple sub-lineages. Genomic analyses of hMPV strains enable monitoring of viral evolution and transmission to inform future interventions but remain underutilized in Africa. METHODS: We generated 52 near-complete hMPV genomes from respiratory samples collected in Kilifi, Coastal Kenya, using a tiled-amplicon approach and Oxford Nanopore Technologies sequencing. These samples had been identified as hMPV positive by quantitative PCR during (a) a multi-facility outpatient ARI surveillance in nine health facilities in Kilifi between 2016 and 2017, and 2021 to 2023 and (b) a community-based respiratory infection cohort surveillance study between 2023-2024 that sampled enrolled participants irrespective of symptom status. RESULTS: Of the 192 positive samples analyzed from the two studies, children under 5 years accounted for most hMPV cases (134/186, 72%). 52 samples were sequenced (>70% genome coverage), and hMPV-A (27/52, 53.8%) and hMPV-B (25/52, 46.2%) lineages were identified. The recovered sequences mapped into sub-lineages A2c (27/52, 53.8%), B1 (12/52, 21.2%), and B2b (13/52, 25%). A shift in the predominant sub-lineage was observed from B2b (2016) to B1 (2021), and finally to A2c-wild type (2023). In February 2021, for the first time, we detected a single A2c strain with a 111-nucleotide duplication in the G gene among Kenyan samples. CONCLUSION: Our study expands the global nucleotide sequence database for hMPV by adding new whole-genome sequences from Kenya collected over the last decade. It highlights the ongoing replacement of locally predominant hMPV lineages and the importation and local transmission of globally circulating strains. These findings underscore the importance of sustained hMPV genomic surveillance to detect emerging variants and monitor lineage circulation patterns that may impact viral transmission, molecular detection, and future control measures.

A2c-111nt-dup↗

PubMed2025

One thousand SARS-CoV-2 antibody structures reveal convergent binding and near-universal immune escape.

Understanding antibody recognition and adaptation to viral evolution is central to vaccine and therapeutic development. Over 1,100 SARS-CoV-2 antibody structures have been resolved, marking the largest structural biology effort for a single pathogen. We present a comprehensive analysis of this landmark dataset to investigate the principles of antibody recognition and immune escape. Human immunoglobulins and camelid single-chain antibodies dominate, collectively mapping 99% of the receptor-binding domain. Despite remarkable sequence and conformational diversity, antibodies exhibit convergence in their paratope structures, revealing evolutionary constraints in epitope selection. Analyses reveal near-universal immune escape of antibodies, including all clinical monoclonals, by advanced variants such as KP3.1.1. On average, over one-third of antibody epitope residues are mutated. These findings support pervasive immune escape, underscoring the need to effectively leverage multi-epitope-targeting strategies to achieve durable immunity. To support community accessibility, we developed an interactive web server for visualization and analysis of antibody-antigen complexes and mutational data.

SARS-CoV-2↗

PubMed2025

Biochemical assays for AID/APOBECs and the identification of AID/APOBEC inhibitors.

Activation-induced cytidine deaminase (AID) and apolipoprotein B-mRNA editing catalytic polypeptide 3 (APOBEC3 or A3) proteins belong to the AID/APOBEC family of cytidine deaminases. While AID mediates somatic hypermutation and class-switch recombination in adaptive immunity, A3s restrict viruses and retroelements by hypermutation. Mis-regulated expression and off-target activity of AID/A3 can cause genome-wide mutations promoting oncogenesis, immune evasion, and therapeutic resistance due to tumor and viral evolution. In these contexts, inhibition of AID/A3 represents a promising therapeutic approach. Competitive inhibition could be achieved with different strategies: one class would be small molecules that bind in the catalytic pocket (active site) and block access for the substrate cytidine. Another type of larger molecule inhibitor would bind the enzymes' surface more broadly and compete with the binding of the polynucleotide substrates prior to deamination catalysis. Several biochemical assays developed to assess AID/A3 activity can be employed to screen for potential inhibitors. These include in cellulo and in vitro activity-based as well as binding-based assays. In this chapter, we discuss the key considerations for designing robust enzyme assays and provide an overview of assays that we and others have established or modified for specific applications in AID/A3 enzymology, including measurement of inhibition. We provide detailed protocols for the two most widely used in vitro enzyme assays that directly measure the activities of purified AID/A3s on DNA and/or RNA substrates, namely, the gel-based alkaline cleavage assay and multiple variations of PCR/sequencing-based assays.

Cytidine Deaminase↗

PubMed2026

An enhanced multisegment RT-PCR method for influenza A virus sequencing: Improved performance and reduced preparation time over traditional methods.

Influenza A viruses (IAVs) remain a major global health threat, affecting both human and animal populations. Whole-genome sequencing is essential for monitoring viral evolution, zoonotic transmission, and emerging variants. However, conventional RT-PCR methods often result in incomplete gene coverage, amplification biases, and reduced sequencing accuracy, particularly in clinical samples. We developed a robust In-house method for IAV full-genome sequencing using the Oxford Nanopore Technologies (ONT) long-read sequencing platform. This method integrates an in-house multisegment Reverse Transcription PCR (RT-PCR) method with a streamlined 2-pool primer design targeting all eight IAV gene segments. RNA extracted from clinical and stock virus samples was reverse-transcribed and amplified using Superscript IV-based chemistry, followed by magnetic bead purification to ensure high-quality amplicons. Sequencing libraries were prepared with the Native Barcoding Kit 24 (SQK-NBD114.24) and sequenced on R10.4.1 flow cells on the MinION MK1C device. Data analysis using the Iterative Refinement Meta-Assembler (IRMA) confirmed improved read depth, uniform coverage, and complete genome recovery. Compared to conventional methods, our In-House Multisegment 2-Pool (IH-MS2P) RT-PCR method generated higher numbers of matched read counts, minimized chimeric artifacts, and delivered superior genome coverage across human, swine, and avian isolates. This optimized RT-PCR method provides a high-performance, time-efficient, and portable solution for influenza genomics, demonstrating robust applicability even with clinical samples of low RNA yield.

Influenza A virus↗

PubMed2026

Endemic Circulation and Genetic Characterization of Foot-and-Mouth Disease Virus in Buffalo Populations of Bangladesh.

Foot-and-mouth disease (FMD) virus (FMDV) is endemic in Bangladesh, causing severe economic losses in the livestock sector. While it primarily affects cattle, buffaloes (Bubalus bubalis) remain highly susceptible. Therefore, this study aimed to determine the prevalence and molecular characteristics of FMDV in buffaloes across three districts (Sylhet, Rajshahi, and Noakhali) of Bangladesh from January to June 2024. In a cross-sectional study, a total of 622 nasal swabs from 67 herds were collected and tested for FMDV RNA using reverse transcription polymerase chain reaction (RT-PCR). Overall, 255 samples were positive, resulting in an individual-level prevalence of 41.0%(255/622), while 88.1% (59/67) of herds were FMDV-positive. Animal-level prevalence was highest in Sylhet (47.1%), followed by Noakhali (38.9%) and Rajshahi (37.1%). To further characterize circulating strains, eight representative RT-PCR-positive samples were sequenced, revealing the co-circulation of serotypes O (n = 5) and Asia-1 (n = 3). Phylogenetic analysis showed that the isolates belonged to the ME-SA/Ind2001e lineage of the serotype O and the Asia-1 Group V lineage, clustering with contemporary strains from Bangladesh and neighboring countries, suggesting possible intra- and transboundary transmission. Pairwise genetic distance evaluation revealed high regional similarity, while Mantel tests indicated significant associations between genetic, geographic, and temporal distances. Comparative genomic analysis revealed largely conserved genomic regions, whereas VP1 analysis indicated that purifying selection predominated across both serotypes, with serotype O exhibiting greater genetic diversity (π = 0.11642) than Asia-1 (π = 0.05258), suggesting localized antigenic variability and possible immune-mediated viral evolution. These findings highlight the need for strengthened surveillance, improved biosecurity, and integrated vaccination strategies to enhance FMD control and reduce economic losses in Bangladesh.

Animals↗

PubMed2026

A comprehensive overview of monkeypox virus disease.

BACKGROUND: Monkeypox (mpox), caused by monkeypox virus (MPXV), re-emerged as a major global public health concern in 2022, resulting in widespread transmission beyond traditionally endemic regions. As of March 2026, 181,164 confirmed cases and 492 deaths had been reported across 144 countries globally. The unprecedented geographic spread of the outbreak highlighted important knowledge gaps in disease surveillance, prevention, and control. Given the ongoing global circulation of MPXV and the risk of future outbreaks, this review provides a comprehensive synthesis of current evidence on MPXV and mpox. METHODS: The literature, surveillance data, and public health reports available up to March 2026 were systematically reviewed and synthesized. The review comprehensively assesses viral biology, genetic diversity, epidemiology, transmission dynamics, clinical manifestations, pathogenesis, laboratory diagnosis, infection during pregnancy, host immune responses, immune evasion mechanisms, therapeutic interventions, and prevention strategies. FINDINGS AND CONCLUSIONS: Globally, the decline in public immunity following the cessation of routine smallpox vaccination, together with ongoing viral evolution, may have contributed to the resurgence of mpox. Advances in genomic surveillance, diagnostics, and public health preparedness have strengthened outbreak response; however, important gaps remain in understanding long-term immunity and optimal treatment strategies. This review summarizes current evidence on MPXV and mpox and highlights priorities for future research and public health interventions.

Antiviral therapy↗

PubMed2025

Defective but tumorigenic: the evolutionary and functional roles of mutated oncoviruses.

Human oncogenic viruses contribute significantly to the global health burden and include seven types: Epstein-Barr virus, hepatitis B virus, human T-cell leukemia virus type 1, human papillomavirus, hepatitis C virus, Kaposi's sarcoma-associated herpesvirus, and Merkel cell polyomavirus. While the roles of latent or integrated viral genomes in cancer have been documented, emerging evidence highlights the contribution of defective viruses-those carrying intragenic deletions or loss-of-function mutations-in promoting viral oncogenesis. These altered genomes often lack genes essential for lytic replication or immune recognition, which enhances their persistence and immune evasion. In virus-associated diseases, specific patterns of gene retention and deletion suggest that host-driven selective pressures drive the emergence of these altered genomes. This review examines the generation, prevalence, and functional impact of these viruses, reframing them as active participants in disease development and progression. Recognizing their role offers new insights into viral tumor evolution and creates opportunities for applications in viral diagnostics and targeted intervention strategies.

Humans↗

PubMed2027

Nanopore Sequencing for Chikungunya Virus: Principles and Application.

Nanopore sequencing is transforming viral genomics through real-time, portable, long-read analysis of RNA and DNA. Unlike traditional short-read platforms, it detects nucleotide sequences by measuring ionic current changes as nucleic acids pass through nanoscale pores, enabling direct single-molecule sequencing and base modification detection. Its simplicity, flexibility, and capacity for ultra-long reads make it ideal for resolving complex genomic regions, structural variants, and full viral genomes. These advantages have accelerated its use in pathogen surveillance and outbreak response, especially in resource-limited settings. For chikungunya virus (CHIKV), nanopore sequencing allows rapid, culture-independent recovery of complete genomes from clinical and vector samples, enabling real-time tracking of viral diversity, evolution, and spread. Experiences from Ebola, Zika, and COVID-19 have demonstrated the power of portable sequencing, now applied to CHIKV monitoring. Advances in tools such as Guppy, Dorado, Minimap2, and Medaka enhance read quality, consensus accuracy, and downstream analyses. Despite challenges in basecalling and error correction, robust quality control pipelines ensure reliable results. Ongoing improvements in chemistry, flow cell design, and machine learning will further enhance fidelity and throughput, establishing nanopore sequencing as a cornerstone of CHIKV genomic surveillance and epidemic preparedness.

Chikungunya virus↗

PubMed2026

Virome-wide ubiquitin ligase discovery reveals diverse mechanisms of immune evasion.

Viruses are intracellular parasites that reprogram the host proteome to promote replication and evade immune recognition. We applied a virome-wide library of ~10,000 open reading frames to discover viral ubiquitin ligases, mapping their mechanisms of degradation and host substrates using targeted CRISPR screens and proteomics. These viral effectors could be classified as canonical ligases that mimic host E3s, hijackers that redirect host E3s, and noncanonical ligases that rewire cullin-RING ligase machinery. These diverse strategies of virus-mediated degradation converged on immune-related substrates, including JAK1 and CUL1β-TrCP, underscoring immune evasion as a major driver of viral ubiquitin ligase evolution. Our findings elucidate viral strategies for exploiting the ubiquitin-proteasome system with potential for therapeutic targeting.

Humans↗

PubMed2024

TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution.

The accessory protease transmembrane protease serine 2 (TMPRSS2) enhances severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uptake into ACE2-expressing cells, although how increased entry impacts downstream viral and host processes remains unclear. To investigate this in more detail, we performed infection assays in engineered cells promoting ACE2-mediated entry with and without TMPRSS2 coexpression. Electron microscopy and inhibitor experiments indicated TMPRSS2-mediated cell entry was associated with increased virion internalization into endosomes, and partially dependent upon clathrin-mediated endocytosis. TMPRSS2 increased panvariant uptake efficiency and enhanced early rates of virus replication, transcription, and secretion, with variant-specific profiles observed. On the host side, transcriptional profiling confirmed the magnitude of infection-induced antiviral and proinflammatory responses were linked to uptake efficiency, with TMPRSS2-assisted entry boosting early antiviral responses. In addition, TMPRSS2-enhanced infections increased rates of cytopathology, apoptosis, and necrosis and modulated virus secretion kinetics in a variant-specific manner. On the virus side, convergent signatures of cell-uptake-dependent innate immune induction were recorded in viral genomes, manifesting as switches in dominant coupled Nsp3 residues whose frequencies were correlated to the magnitude of the cellular response to infection. Experimentally, we demonstrated that selected Nsp3 mutations conferred enhanced interferon antagonism. More broadly, we show that TMPRSS2 orthologues from evolutionarily diverse mammals facilitate panvariant enhancement of cell uptake. In summary, our study uncovers previously unreported associations, linking cell entry efficiency to innate immune activation kinetics, cell death rates, virus secretion dynamics, and convergent selection of viral mutations. These data expand our understanding of TMPRSS2's role in the SARS-CoV-2 life cycle and confirm its broader significance in zoonotic reservoirs and animal models.

SARS-CoV-2↗

PubMed2026

The factory enters the fray: how mitochondrial protein trafficking shapes the host response to infection.

Beyond textbook functions in homeostatic metabolism, mitochondria are now recognized as central coordinators of cell-intrinsic and cell-extrinsic immune responses to infection. Directed trafficking of proteins and other molecules between mitochondria and the rest of the cell underlies a growing catalog of these activities. Some are pro-host; others are antagonized by viral effectors or co-opted by viruses entirely. How host and viral factors rewire the mitochondrial proteome during infection to shape these outcomes remains incompletely understood. The evolutionary history of this system adds another dimension: mitochondria retain biochemical signatures of their α-proteobacterial endosymbiotic origin, and ongoing co-evolution between viral, host, and mitochondrial genomes continues to shape the proteins that traffic to and from the organelle. Using published examples, we highlight general principles, mechanisms, and consequences of host and viral protein localization to and from the mitochondria. To support discovery, we present integrated gene lists identifying host mitochondrial factors with evidence for type I interferon stimulation, interactions with viral proteins, and signatures of positive selection. Together, these resources and the principles within offer a framework for understanding mitochondria not as passive metabolic machinery but as actively contested cellular territory whose protein composition is continuously negotiated between the host and the pathogen.

adaptation↗

PubMed2025

Experimental Evolution of Poxviruses.

Experimental evolution is the process of exposing virus populations to defined selective pressures in a laboratory setting to identify adaptive changes. Coupled with deep sequencing, this experimental approach allows for nucleotide-level resolution of poxvirus adaptive strategies over time. Here, we present a general method of poxvirus experimental evolution, Illumina-based deep sequencing, and bioinformatic analyses to identify structural changes (e.g., gene duplication) as well as local adaptive changes (e.g., small indels and single nucleotide polymorphisms).

Poxviridae↗

PubMed2026

Three thousand five hundred years of sheeppox virus evolution inferred from archaeological and codicological genomes.

Sheeppox virus (SPPV) is a major livestock pathogen causing economic hardship through reduced production and death of vulnerable sheep, with written descriptions of sheeppox-like disease recorded since antiquity. We report 21 novel ancient SPPV genomes spanning the Eurasian steppe Bronze Age (∼1700 BCE) to the Early Modern period in Western Europe, including multiple genomes obtained from medieval parchment. We estimate that major capripoxvirus lineages diverged ∼11,500 to 3700 years ago, overlapping known translocations and bio-cultural developments in sheep. Our dataset supports SPPV diverging first within the lineage leading to goatpox virus and lumpy skin disease virus, and that known gene inactivation events within SPPV and goatpox virus occur in our earliest SPPV genomes. These findings reveal that the food security of Eurasian communities has been threatened by sheeppox for more than 3700 years and provide insights into the genomic evolution and potential host adaptation of SPPV.

Animals↗