Frontiers in Virology

Evolutionary dynamics of Erinaceus coronavirus in Italy: spike protein adaptation and variable CD200 ortholog insertion

2026-04-01

Luca De Sabato, Ilaria Di Bartolo, Irene Berselli, Giovanni Ianiro, Marina Monini, Monica Giammarioli, Marco Gobbi, Riccardo Orusa, Serena Robetto, Maria Lucia Mandola, Chiara Nogarol, Ana Moreno, Davide Lelli, Claudia Cotti, Mauro Delogu, Maria Alessandra De Marco, Stefania Leopardi, Francesca Festa, Manuela Marra, Valentina Libri, Stefania Pulcini, Francesca Manzia, Roberto Nardini, Maria Teresa Scicluna, Antonella Cersini, Claudia Eleni, Giulia Pacchiarotti, Gianluca Nocco, Maria Teresa Capucchio, Gabriele Vaccari

IntroductionIn 2013, a novel coronavirus (CoV) species was identified in European hedgehogs (Erinaceus europaeus) in Germany. Since then, only a limited number of studies reported the circulation of this virus, recognized as Erinaceus coronavirus (EriCoV), and demonstrated its evolutionary relationship with Middle East respiratory syndrome coronavirus (MERS-CoV). Given that MERS-CoV is one of the three zoonotic coronaviruses known to cause severe disease in humans, these findings raise concerns about the zoonotic potential of EriCoV strains. In a previous study conducted in Italy, eight complete EriCoV genomes were obtained from hedgehogs sampled in Northern Italy, revealing substantial genetic heterogeneity among circulating strains. Genome analyses also identified the insertion of a gene encoding the CD200 ortholog, containing a short region potentially involved in host immune modulation. The present study aimed to investigate the circulation and genetic diversity of coronaviruses in hedgehogs from different areas of Italy and to assess the occurrence and distribution of the CD200 ortholog insertion. MethodsComplete EriCoV genomes were obtained from 35 hedgehogs using Next Generation Sequencing (NGS) by Ion Torrent machine. For an additional 20 animals, full genome sequences could not be generated; therefore, sequences were obtained by nested RT-PCR amplifying partial sequences of the RNA-dependent RNA polymerase (RdRp) gene and, when present, on the CD200 insertion. Phylogenetic analysis of sequences obtained were performed. ResultsPhylogenetic analysis revealed no clear geographic clustering, with sequences from Northern Italy interspersed with those from Central and Southern Italy. Analysis of the spike (S) protein identified 25 sites evolving under positive selection, three of which were located within the receptor-binding domain (RBD). The CD200 ortholog was confirmed in 15 complete genomes and in 5 additional samples by RT-PCR, collected from both Northern and Southern Italy. DiscussionOverall, the study confirms that EriCoV related strains are found across the country. A CD200 insertion appears in both Northern and Southern regions, but it is not consistently present, indicating that this insertion is not fixed within the viral population. Sites found under positive selection in spike protein, including three in the receptor-binding domain, that may be relevant for host–virus interactions and merit further investigation in the context of cross-species transmission risks.

Toward efficient surveillance: a proof-of-concept comparison of methods for detecting DNA and RNA viruses in wastewater

2026-03-27

Marek Samec, Ivana Baranová, Renata Péčová, Martin Péč, Elena Nováková, Iryna Samec, Vincent Lučanský

Wastewater-based epidemiology (WBE) represents a promising method for early detection and ongoing monitoring of various pathogens. This epidemiological approach has recently attracted significant research interest. During the SARS-CoV-2 pandemic, WBE was estimated as a complementary surveillance tool for mapping the spread of the virus within the population. Although this method has great potential for pathogen monitoring at both local and national levels, there are some limitations, notably the presence of high concentrations of inhibitors that contaminate extracted nucleic acids from wastewater, which can lead to false negative results. This proof-of-concept study focuses on detecting RNA and DNA viruses, specifically SARS-CoV-2 and adenovirus, in wastewater by droplet digital PCR (ddPCR) and compares the results with those obtained with the routinely used RT-qPCR and qPCR methods. The results of our proof-of-concept study indicate that WBE represents a promising approach for monitoring pathogens such as SARS-CoV-2 and adenovirus; however, challenges such as contaminants in wastewater need to be addressed to increase detection accuracy. Due to this limitation, novel technologies such as ddPCR offer new opportunities to improve epidemiological monitoring of various infectious agents in the population.

Multicompartment modeling of influenza A replication along the murine respiratory tract

2026-03-11

Rodolfo Blanco-Rodriguez, L. America Chi, Esteban A. Hernandez-Vargas

Influenza A virus spreads through the respiratory tract in a compartment-specific manner, yet the mechanisms governing its progression remain unclear. Here, we investigated how viral replication and inter-compartment transport shape infection dynamics across the nose, trachea, and lungs. To address this, we developed a multicompartment mathematical model based on a target-cell framework and fitted it to reported viral-load data from mice infected with the Udorn H3N2 strain, using bootstrap estimation to quantify uncertainty. The best-performing model revealed rapid amplification and substantial target-cell depletion in the nose, limited replication, and delayed viral dynamics in the lungs, mainly driven by input from upstream compartments. Transport parameters exceeded local replication rates in deeper regions, indicating that the nose serves as the primary site of viral replication and seeding. Overall, this study highlights the dominant role of the nasal compartment in driving within-host influenza progression.

Innovating virology: from empirical verification to hypothesis exploration

2026-02-12

Akio Adachi, Yuma Inamoto, Khanh Quoc Tran, Bao Quoc Le, Naoya Doi, Takaaki Koma, Masako Nomaguchi

Editorial: Proceedings of the first RdRp Summit

2026-02-04

So Nakagawa, Artem Babaian, Simon Roux, Uri Neri

A next-generation strategy for HIV-1 vaccination: computational design of a multi-epitope subunit vaccine targeting global circulating variants

2026-01-30

Sajid Khan, Zarlish Attique, Muhammad Hamza, Lingyu Li, Muhammad Imran, Li Yu, Suping Zhang

Despite decades of research, no effective cure or preventive vaccine exists for human immunodeficiency virus type 1 (HIV-1). To address this gap, this study aimed to design a universal multi-epitope subunit vaccine (MESV) targeting conserved and immunogenic epitopes across diverse HIV-1 variants. Publicly available HIV-1 proteome data were analyzed using an immunoinformatics pipeline that integrates curated immunological databases and epitope-prediction servers, resulting in the identification of 44 conserved epitopes from the core proteome, including twelve newly identified relative to existing databases. The MESV was constructed using 14 linear B-cell epitopes and 30 T-cell epitopes restricted by globally conserved human leukocyte antigen (HLA) alleles, achieving 98.63% MHC-I and 99.67% MHC-II global population coverage. Molecular docking analysis revealed high binding scores and favorable energy values for MESV interactions with toll-like receptor 1 (TLR1) and toll-like receptor 2 (TLR2), suggesting stable antigen recognition. After codon optimization, the MESV (889 aa) was expressed and purified using affinity chromatography, yielding an ~95.1 kDa protein confirmed by immunoblot analysis. In silico immunological simulations demonstrated robust humoral and cellular immune responses following three doses, including elevated IgG antibody levels and increased numbers of memory B cells, cytotoxic CD8+ T cells, and natural killer cells. Overall, this study highlights the potential of a computationally designed MESV to overcome HIV-1 diversity and induce broad-spectrum immunity. These findings warrant further in vitro and in vivo validation to confirm immunogenicity and protective efficacy, paving the way toward the development of a universal HIV-1 vaccine.

Bridging the gap: addressing real-life challenges to the implementation of DTG/3TC in treatment-naive people living with HIV

2026-01-19

Andrea Giacomelli, Gianmaria Baldin, Valeria Bono, Arturo Ciccullo, Maria Mazzitelli, Mariacristina Poliseno, Marco Ridolfi, Federica Sozio, Elisabetta Teti, Giulia Marchetti

Dolutegravir/lamivudine (DTG/3TC), used as a two-drug regimen (2DR), has demonstrated non-inferiority to traditional three-drug regimens (3DRs) in treatment-naive people with HIV (PWH), with sustained virological efficacy, favorable tolerability, and a good safety profile. However, its implementation in routine clinical practice raises several questions, particularly in populations underrepresented in registration trials. This review critically appraises current evidence supporting DTG/3TC as first-line antiretroviral therapy, drawing from randomized clinical trials and real-world studies. Available data indicate that DTG/3TC maintains high virological suppression rates even in individuals with high baseline viral load (>500,000 copies/mL), with no emergent resistance. Evidence from test-and-treat settings suggests comparable efficacy to triple therapy, provided that hepatitis B coinfection and transmitted resistance are adequately excluded. Preliminary data in late presenters and those with advanced disease support its effectiveness, although confirmatory trials are warranted. Beyond viro-immunological outcomes, DTG/3TC appears equivalent to triple regimens in reducing viral reservoirs, immune activation, and systemic inflammation. Evidence in women living with HIV, including during pregnancy, remains limited but reassuring, with no major safety concerns identified. Overall, the body of clinical and real-world evidence supports DTG/3TC as a simplified and durable first-line regimen for most treatment-naive PWH. Ongoing research should further define its role in acute infection, advanced HIV disease, and specific subpopulations such as women and individuals from regions with high prevalence of non-B subtypes.

Dolutegravir-based antiretroviral therapy-associated hyperglycemia in persons living with human immunodeficiency virus in Niger: a multicentric cross-sectional study

2026-01-06

Abdourahamane Yacouba, Ramatou Sidibe, Aboubacar-Sidick Chegou Sonouchi Dalla, Ali Inoussa Issa, Sahada Moussa Saley, Ounoussa Tapha, Abdou Natali Bassirou, Mahamadou Doutchi, Souleymane Brah, Idrissa Massi Abdoul-Wahab, Yacouba Nouhou, Oumi-Ramatou Amidou Ganda, Saidou Mamadou

BackgroundGrowing evidence from clinical and experimental research suggests that dolutegravir is associated with hyperglycemia. This study aimed to determine the prevalence of hyperglycemia and its associated factors among persons living with human immunodeficiency virus (PLWH) on dolutegravir-based antiretroviral therapy in Niger.MethodologyThis was a retrospective multicentric cross-sectional study carried out using data from PLWH who had been examined between January 2022 and June 2024. Data were collected from July to September 2024. PLWH aged 18 years or older who had been on dolutegravir-based antiretroviral therapy for more than three months were enrolled in the study. Hyperglycemia was defined as a fasting plasma glucose level ≥7.0 mmol/L. A multivariable logistic regression analysis was conducted in RStudio version 4.4.1 to identify factors associated with hyperglycemia. Variables with a p-value less than 0.05 were considered statistically significant.ResultsA total of 633 records were reviewed during the study period, of which 39.0% (n = 247) had baseline blood glucose levels and were included in this analysis. The mean age of patients was 38.9 ± 11.8 years. More than half of the patients (60.5%; n = 101) had a normal body mass index. The mean duration of the dolutegravir-based regimen was 13.9 ± 7.05 months. The prevalence of hyperglycemia was 36.4% (n = 51). In multivariate analysis, patients with primary (adjusted Odds ratio (aOR): 8.26; 95% CI: 1.47-62.00, p=0.024), secondary (aOR: 6.29; 95%CI: 1.12-48.28; p=0.051), and tertiary (aOR: 9.39; 95%CI: 1.34-89.92; p=0.034) educational levels, patients with a history of personal hypertension (aOR: 4.24; 95% CI: 1.17-17.18; p = 0.033) were significantly associated with hyperglycemia among PLWH on dolutegravir-based ART regimens.ConclusionThe prevalence of hyperglycemia among PLWH on dolutegravir-based antiretroviral therapy regimens was relatively high in Niger. Educated PLWH and hypertension were identified as risk factors for hyperglycemia. Baseline and periodic monitoring of plasma glucose might be required in antiretroviral therapy containing dolutegravir care in Niger.