Virus Lineage Research Articles

Analysis of the Monophyletic Lineage of Avian Influenza H5N1 Which Circulated in Venezuelan Birds During the 2022–2023 Outbreak

Avian influenza subtype H5N1 has caused outbreaks worldwide since 1996, with the emergence of the Guandong lineage in China. The current clade 2.3.4.4b has evolved from this lineage, with increased virulence and mass mortality events in birds and mammals. The objective of this study was the analysis of 17 viral genomes of H5N1 avian influenza isolated in Venezuela during the 2022–2023 outbreak. The eight viral genomic segments were amplified using universal primers and sequenced via next-generation sequencing. The sequences were analyzed to confirm the H5 hemagglutinin clade, identify possible genetic reassortments, and perform a phylogenetic and docking analysis of the viral isolates. The viruses found in Venezuela belonged, as expected, to clade 2.3.4.4b and formed a monophyletic clade with North American influenza viruses, with no evidence of further reassortment. The introduction of the virus in South America is associated with bird migration through the Atlantic (Venezuela), Atlantic/Mississippi (Choco, Colombia), and Pacific migratory flyways, with the emergence of several viral lineages. Several mutations were found in all segments of the genome, although none of the key mutations was involved in mammalian adaptation. Moreover, in silico structural analysis suggests, as expected, that the viral hemagglutinin maintained a predilection for avian α2,3-linked sialic acid. The unprecedented pathogenic outbreak of avian influenza disease in South America was associated with the circulation of three different lineages, which maintain a lower affinity for the mammalian receptor.

Dengue virus transmission in Italy: historical trends up to 2023 and a data repository into the future

Dengue virus circulation is on the rise globally, with increased epidemic activity in previously unaffected countries, including within Europe. In 2023, global dengue activity peaked, and Italy reported the highest number of dengue cases and local chains of transmission to date. By curating several sources of information, we introduce a novel data repository focused on dengue reporting in Italy. We integrate data from such a repository with other geographic, genomic and climatic spatiotemporal data to present an overview of transmission patterns of the past eight years related to circulating viral lineages, geographic distribution, hotspots of reporting, and the theoretical contribution of local climate. The novel data repository can contribute to a better understanding of an evolving epidemiological scenario in Italy, with the potential to inform reassessment and planning of adequate national and European public health strategies to manage the emergence of the dengue virus.

How fast are viruses spreading in the wild?

Genomic data collected from viral outbreaks can be exploited to reconstruct the dispersal history of viral lineages in a two-dimensional space using continuous phylogeographic inference. These spatially explicit reconstructions can subsequently be used to estimate dispersal metrics that can be informative of the dispersal dynamics and the capacity to spread among hosts. Heterogeneous sampling efforts of genomic sequences can however impact the accuracy of phylogeographic dispersal metrics. While the impact of spatial sampling bias on the outcomes of continuous phylogeographic inference has previously been explored, the impact of sampling intensity (i.e., sampling size) when aiming to characterise dispersal patterns through continuous phylogeographic reconstructions has not yet been thoroughly evaluated. In our study, we use simulations to evaluate the robustness of 3 dispersal metrics - a lineage dispersal velocity, a diffusion coefficient, and an isolation-by-distance (IBD) signal metric - to the sampling intensity. Our results reveal that both the diffusion coefficient and IBD signal metrics appear to be the most robust to the number of samples considered for the phylogeographic reconstruction. We then use these 2 dispersal metrics to compare the dispersal pattern and capacity of various viruses spreading in animal populations. Our comparative analysis reveals a broad range of IBD patterns and diffusion coefficients mostly reflecting the dispersal capacity of the main infected host species but also, in some cases, the likely signature of rapid and/or long-distance dispersal events driven by human-mediated movements through animal trade. Overall, our study provides key recommendations for the use of lineage dispersal metrics to consider in future studies and illustrates their application to compare the spread of viruses in various settings.

SARS-CoV-2 Omicron XBB infections boost cross-variant neutralizing antibodies, potentially explaining the observed delay of the JN.1 wave in some Brazilian regions

ObjectivesThe SARS-CoV-2 JN.1 lineage emerged in late 2023 and quickly replaced the XBB lineages, becoming the predominant Omicron variant worldwide in 2024. We estimate the epidemiological impact of this SARS-CoV-2 lineage replacement in Brazil and we further assessed the cross-reactive neutralizing antibody (NAb) responses in a cohort of convalescent Brazilian patients infected during 2023. MethodsWe analyzed the evolution of SARS-CoV-2 lineages and severe acute respiratory infection (SARI) cases in Brazil between July 2023 and March 2024. We evaluated the cross-reactive NAb responses to the JN.1 variant in a cohort of convalescent Brazilian patients, both before and after infection with XBB.1* lineages. ResultsJN.1 replaced XBB with similar temporal dynamics across all country regions, though its epidemiological impact varied between locations. The Southeastern, Southern, and Central-Western regions experienced a brief XBB wave around October 2023, shortly before the introduction of JN.1, without any immediate upsurge of SARI cases during viral lineage replacement. By contrast, the Northeastern and Northern regions did not experience an XBB wave in the latter half of 2023 and displayed a rapid surge in SARI cases driven by the emergence of the JN.1. We found that recent XBB infections in the Brazilian population significantly boosted cross-reactive NAb levels against JN.1. ConclusionsThe XBB wave observed in the second half of 2023 in some Brazilian states likely acted as a booster for population immunity, providing short-term protection against JN.1 infections and delaying the rise of SARI cases in certain regions of the country.

Lassa fever outbreaks, mathematical models, and disease parameters: a systematic review and meta-analysis

Understanding the epidemiological parameters and transmission dynamics of Lassa fever, a significant public health threat in west Africa caused by the rodent-borne Lassa virus, is crucial for informing evidence-based interventions and outbreak response strategies. Therefore, our study aimed to collate and enhance understanding of the key epidemiological parameters of Lassa fever. We conducted a systematic review, searching PubMed and Web of Science for peer-reviewed studies published from database inception up to June 13, 2024, to compile and analyse key epidemiological parameters, mathematical models, and outbreaks of Lassa fever. English-language, peer-reviewed, original research articles were included if they reported on Lassa fever outbreak sizes, transmission models, viral evolution, transmission, natural history, severity, seroprevalence, or risk factors. Non-peer-reviewed literature was excluded. Data were extracted by two independent individuals from published literature, focusing on seroprevalence, transmissibility, epidemiological delays, and disease severity. We performed a meta-analysis to calculate pooled estimates of case-fatality ratios (CFRs) and the delay from symptom onset to hospital admission. This study is registered with PROSPERO (identifier number CRD42023393345). The database search returned 5614 potentially relevant studies, and a further 16 studies were identified from backward citation chaining. After de-duplication and exclusion, 193 publications met our inclusion criteria and provided 440 relevant parameter estimates in total. Although Lassa virus is endemic in west Africa, the spatiotemporal coverage of general-population seroprevalence estimates (ranging from 2·6% [6/232] to 58·2% [103/177]) was poor, highlighting the spatial uncertainty in Lassa fever risk. Similarly, only four basic reproduction number estimates (ranging from 1·13 to 1·40) were available. We estimated a pooled total random effect CFR of 33·5% (95% CI 25·8-42·2, I2=95%) and found potential variation in severity by geographical regions typically associated with specific Lassa virus lineages. We estimated a pooled total random effect mean symptom-onset-to-hospital-admission delay of 8·19 days (95% CI 7·31-9·06, I2=93%), but other epidemiological delays were poorly characterised in the existing literature. Our findings highlight the absence of empirical Lassa fever parameter estimates despite its high burden in west Africa. Improved surveillance approaches to capture mild cases in humans and to further cover rodent populations are needed to better understand Lassa fever transmission dynamics. Addressing these gaps is essential for developing accurate mathematical models and informing evidence-based interventions to mitigate the effect of Lassa fever on public health in endemic regions. UK Medical Research Council, National Institute for Health and Care Research, Academy of Medical Sciences, Wellcome, UK Department for Business, Energy, and Industrial Strategy, British Heart Foundation, Diabetes UK, Schmidt Foundation, Community Jameel, Royal Society, and Imperial College London. For the French translation of the abstract see Supplementary Materials section.

Genomic epidemiology of invasive Group A Streptococcus infections in Argentina, 2023: high prevalence of emm1-global and detection of emm1 hypervirulent lineages.

The aim of this study is to describe the genomic epidemiology of invasive Group A Streptococcus (iGAS) in Argentina during 2023. A total of 476 invasive GAS isolates were subtyped and analyzed by whole-genome sequencing. A high prevalence of the emm1-type strain was observed. Among the emm1 strains, two highly virulent international variants, emm1-UK and emm1-DK, were identified. Additionally, a local variant, called emm1-ST1319, was detected. This seminal study provides initial insights into the genomic landscape of iGAS, contributing to active surveillance to monitor emerging virulent emm1 lineages and cross-border transmission in South America.IMPORTANCEAmid the increase in invasive Streptococcus pyogenes infections in Argentina in 2023, the implementation of genomic analysis of isolates allowed us to detect at the national level the prevalence of the emm1 type and within the M1 type, emerging national and international hypervirulent lineages. These findings from our report shed light on the distribution of invasive Group A Streptococcus, laying the foundation for genomic surveillance of this pathogen.

In vitro and in vivo characterization of a novel West Nile virus lineage 2 strain

Over recent decades, West Nile virus (WNV) has continued to expand its geographical range, emerging in previously non-endemic areas, including northern Europe. In Europe, WNV lineage 2 strains are most prevalent and cause sporadic outbreaks of WNV disease in humans each transmission season. Here, we assessed the virulence of a newly emerged WNV lineage 2 strain that was isolated in the Netherlands in 2020 (WNV-NL20) and caused several cases of West Nile disease in humans and used a WNV lineage 2 strain related to major outbreaks of neuroinvasive disease in humans in central and south-eastern Europe in 2010 (WNV-578/10) as a reference. Infection of primary human cells of the blood-brain barrier in vitro did not show major differences in replication kinetics between WNV-578/10 and WNV-NL20. Experimental infection of mice showed that both WNV strains induced significant weight loss, neurological signs, and lethal disease. Neurological involvement was confirmed for both WNV strains by the presence of infectious virus and viral antigen in the brain. In conclusion, we show that the recent WNV-NL20 strain that emerged in the Netherlands is neurovirulent in mice. The use of in vitro and in vivo models to characterize the pathogenesis of emerging WNV strains may aid in predicting the neurovirulence of WNV infections in humans during potential future outbreaks.

Discovery and characterization of complete genomes of 38 head-tailed proviruses in four predominant phyla of archaea.

Archaea play a significant role in natural ecosystems and the human body. Archaeal viruses exert a considerable influence on the structure and composition of archaeal communities and their associated ecological environments. The present study revealed the complete genomes of 38 archaeal head-tailed proviruses through comprehensive data mining. The hosts of these proviruses were identified as belonging to the following four dominant phyla: Halobacteriota, Thermoplasmatota, Thermoproteota, and Nanoarchaeota. In addition to the 14 proviruses of halophilic archaea related to the Graaviviridae family, the remaining proviruses exhibited limited genetic similarities to known (pro)viruses, suggesting the existence of 14 potential novel families. Of the 38 archaeal proviruses, 30 have the potential to lyse host cells. Eleven proviruses contain genes linked to antiviral defense mechanisms, including those involved in restriction modification (RM), clustered regularly interspaced short palindromic repeat (CRISPR)-associated (CRISPR-Cas) nucleases, defense island system associated with restriction-modification (DISARM), and DNA degradation (Dnd). Moreover, auxiliary metabolic genes were identified in the proviruses of Bathyarchaeia and Halobacteriota archaea, including those involved in carbohydrate and amino acid metabolism. Our findings indicate the diversity of archaeal viruses, their interactions with archaeal hosts, and their roles in the adaptation of the host.IMPORTANCEThe field of archaeal virology has seen a rapid expansion through the use of metagenomics, yet the diversity of these viruses remains largely uncharted. In this study, the complete genomes of 38 novel archaeal proviruses were identified for the following four dominant phyla: Halobacteriota, Thermoplasmatota, Thermoproteota, and Nanoarchaeota. Two families and six genera of Archaea were the first to be identified as hosts for viruses. The proviruses were found to contain diverse genes that were involved in distinct adaptation strategies of viruses to hosts. Our findings contribute to the expansion of the lineages of archaeal viruses and highlight their intricate interactions and essential roles in enabling host survival and adaptation to diverse environmental conditions.

Unveiling bat-borne viruses: a comprehensive classification and analysis of virome evolution

BackgroundBats (Order Chiroptera) are an important reservoir of emerging zoonotic microbes, including viruses of public health concern such as henipaviruses, lyssaviruses, and SARS-related coronaviruses. Despite the continued discovery of new viruses in bat populations, a significant proportion of these viral agents remain uncharacterized, highlighting the imperative for additional research aimed at elucidating their evolutionary relationship and taxonomic classification.ResultsIn order to delve deeper into the viral reservoir hosted by bats, the present study employed Next Generation Sequencing (NGS) technology to analyze 13,105 swab samples obtained from various locations in China. Analysis of 378 sample pools revealed the presence of 846 vertebrate-associated viruses. Subsequent thorough examination, adhering to the International Committee on Taxonomy of Viruses (ICTV) criteria for virus classification, identified a total of 120 putative viral species with the potential to emerge as novel viruses, comprising a total of 294 viral strains. Phylogenetic analysis of conserved genomic regions indicated the novel virus exhibited a diverse array of viral lineages and branches, some of which displayed close genetic relationships to known human and livestock pathogens, such as poxviruses and pestiviruses.ConclusionsThis study investigates the breadth of DNA and RNA viruses harbored by bats, delineating several novel evolutionary lineages and offering significant contributions to virus taxonomy. Furthermore, the identification of hitherto unknown viruses with relevance to human and livestock health underscores the importance of this study in encouraging infectious disease monitoring and management efforts in both public health and veterinary contexts.5R8JHumEnvkqKNe4tF9zBoVideo

Post-disappearance scenarios: policy implications following the potential disappearance of B/Yamagata lineage influenza viruses.

The COVID-19 pandemic and related preventive measures reduced influenza virus circulation, notably causing the disappearance of the B/Yamagata lineage of influenza viruses. In this Perspective, we discuss the implications that this development may have for global influenza epidemiology, and the adjustments that may need to be implemented concerning surveillance strategies and practices, laboratory safety protocols, and influenza vaccine formulations. The disappearance of the B/Yamagata lineage might indeed alter the dynamics of the influenza disease burden (although in a way that is difficult to predict at the moment), and associated diagnostic practices, and may also necessitate updated biosafety levels and revised influenza surveillance strategies. Furthermore, the World Health Organization (WHO) recommended in September 2023 the exclusion of B/Yamagata antigens from future vaccines, with a shift towards trivalent vaccines or modified quadrivalent vaccines; this new scenario underscores the importance of robust global respiratory virus surveillance, effective communication with healthcare professionals and the population to maintain trust in vaccines, and a collaborative approach among health policymakers and vaccine manufacturers to navigate this epidemiological change.

Genomic surveillance of Canadian airport wastewater samples allows early detection of emerging SARS-CoV-2 lineages

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has shown wastewater (WW) surveillance to be an effective means of tracking the emergence of viral lineages which arrive by many routes of transmission including via transportation hubs. In the Canadian province of Ontario, numerous municipal wastewater treatment plants (WWTPs) participate in WW surveillance of infectious disease targets such as SARS-CoV-2 by qPCR and whole genome sequencing (WGS). The Greater Toronto Airports Authority (GTAA), operator of Toronto Pearson International Airport (Toronto Pearson), has been participating in WW surveillance since January 2022. As a major international airport in Canada and the largest national hub, this airport is an ideal location for tracking globally emerging SARS-CoV-2 variants of concern (VOCs). In this study, WW collected from Toronto Pearson’s two terminals and pooled aircraft sewage was processed for WGS using a tiled-amplicon approach targeting the SARS-CoV-2 virus genome. Data generated was analyzed to monitor trends of SARS-CoV-2 lineage frequencies. Initial detections of emerging lineages were compared between Toronto Pearson WW samples, municipal WW samples collected from the surrounding regions, and Ontario clinical data as published by Public Health Ontario. Results enabled the early detection of VOCs and individual mutations emerging in Ontario. On average, the emergence of novel lineages at the airport preceded clinical detections by 1–4 weeks, and up to 16 weeks in one case. This project illustrates the efficacy of WW surveillance at transitory transportation hubs and sets an example that could be applied to other viruses as part of a pandemic preparedness strategy and to provide monitoring on a mass scale.

Dengue Outbreak Caused by Multiple Virus Serotypes and Lineages, Colombia, 2023-2024.

Dengue cases rose to record levels during 2023-2024. We investigated dengue in Valle del Cauca, Colombia, to determine if specific virus serotypes or lineages caused its large outbreak. We detected all 4 serotypes and multiple lineages, suggesting that factors such as climatic conditions were likely responsible for increased dengue in Colombia.

Co-Circulation of 2 Oropouche Virus Lineages, Amazon Basin, Colombia, 2024.

In early 2024, explosive outbreaks of Oropouche virus (OROV) linked to a novel lineage were documented in the Amazon Region of Brazil. We report the introduction of this lineage into Colombia and its co-circulation with another OROV lineage. Continued surveillance is needed to prevent further spread of OROV in the Americas.

Population dynamics of defective viral genomes of tomato black ring virus during host-to-host transmission.

Defective viral genomes (DVGs) have been identified in vivo and in vitro for different virus species infecting humans, animals, and plants. The ability to form DVGs during the passaging of virus in one host has been demonstrated, i.e., for tomato black ring virus (TBRV). In our research, RNA-Seq data obtained after TBRV passaging through a combination of four distinct host species were analyzed. Our results indicate that the level of DVG abundance varied across host plant combinations. Deletions were the most prevalent class of DVGs, with the domination of longer species. Additionally, the conserved junction sites in the TBRV genome were identified, resulting in the generation of identical deletions in independently evolved viral lineages. In summary, our findings provide significant insights into the origin and structure of DVGs of plant viruses. The obtained results will help in understanding viral evolution and host-virus interactions.

Dynamics and ecology of a multi-stage expansion of Oropouche virus in Brazil.

In March 2024, the Pan American Health Organization (PAHO) issued an alert in response to a rapid increase in Oropouche fever cases across South America. Brazil has been particularly affected, reporting a novel reassortant lineage of the Oropouche virus (OROV) and expansion to previously non-endemic areas beyond the Amazon Basin. Utilising phylogeographic approaches, we reveal a multi-scale expansion process with both short and long-distance dispersal events, and diffusion velocities in line with human-mediated jumps. We identify forest cover, banana and cocoa cultivation, temperature, and human population density as key environmental factors associated with OROV range expansion. Using ecological niche modelling, we show that OROV circulated in areas of enhanced ecological suitability immediately preceding its explosive epidemic expansion in the Amazon. This likely resulted from the virus being introduced into simultaneously densely populated and environmentally favourable regions in the Amazon, such as Manaus, leading to an amplified epidemic and spread beyond the Amazon. Our study provides valuable insights into the dispersal and ecological dynamics of OROV, highlighting the role of human mobility in colonisation of new areas, and raising concern over high viral suitability along the Brazilian coast.

Emergence of ECSA-IOL E1-K211E/E2-V264A Lineage of Chikungunya virus during Malaysian 2021 outbreak

BackgroundChikungunya cases was reported to be on the rise in Malaysia from 2019 to 2021. Although potential endemicity was described previously, genotype shift during 2008 outbreak originating from the 2004 Indian Ocean Islands outbreak presents the probability of current CHIKV spread from neighboring countries. This is due to the prevalence of the new IOL sub-lineage which consists of E1-226A wildtype or reverted strains that are circulating in the Indian subcontinent before spreading to neighboring Thailand during 2018–2019 outbreak.MethodIn this study, samples received mostly from the Tangkak, Johor were analyzed. A total 56 CHIKV positive serum samples received in 2021 by Institute of Medical Research Malaysia (IMR), were collected based on sample selection criteria. Selected samples were subjected to total RNA extraction, whole-genome sequencing as well as bioinformatic analysis such as phylogenetic, variant and mutation analysis.ResultsBased on the genomic and phylogenetic analysis, the CHIKV samples from 2021 outbreak were of ECSA-IOL genotype. Genome similarity analysis also revealed that these CHIKVs were highly similar to 2018–2019 outbreak strain from Thailand. In comparison to the 2008 outbreak CHIKV isolate, the current CHIKVs lacked the E1-A226V mutation and harbored the new E1-K211E/E2-V264A sub-linage mutation. Since the E1-K211E/E2-V264A mutation facilitates adaptation to Ae. aegypti as opposed to the E1-A226V mutation which improves adaptation to Ae. albopictus, the emergence 2021 CHIKV outbreak in Malaysia can be postulated due to vector shift. Interestingly, a novel nsP3-T441A/V mutation detected in this study, may also play a role in virus transmission, pathogenicity, fitness and vector adaptation.ConclusionIn summary, the current CHIKV outbreak are strains originated from the Indian subcontinent through Thailand which may have capitalized on vector shifting by adapting to Ae. aegypti. The presence of novel nsP3-T441A/V mutation may also contribute to the spread of this virus across peninsular Malaysia.

Multi-drug resistant Staphylococcus epidermidis from chronic wounds impair healing in human wound model.

Venous leg ulcers (VLUs) represent one of the most prevalent types of chronic wounds characterised by perturbed microbiome and biofilm-forming bacteria. As one of the most abundant skin-commensal, Staphylococcus epidermidis is known as beneficial for the host, however, some strains can form biofilms and hinder wound healing. In this study, S. epidermidis distribution in VLUs and associated resistome were analysed in ulcer tissue from patients. Virulence of S. epidermidis isolates from VLUs were evaluated by whole genome sequencing, antimicrobial susceptibility testing, in vitro biofilm and binding assays, and assessment of biofilm-forming capability and pro-inflammatory potential using human ex vivo wound model. We demonstrated that S. epidermidis isolates from VLUs inhibit re-epithelialization through biofilm-dependent induction of IL-1β, IL-8, and IL-6 which was in accordance with impaired healing outcomes observed in patients. High extracellular matrix binding ability of VLU isolates was associated with antimicrobial resistance and expression levels of the embp and sdrG, responsible for bacterial binding to fibrinogen and fibrin, respectively. Finally, we showed that S. epidermidis from VLUs demonstrate pathogenic features with ability to impair healing which underscores the emergence of treatment-resistant virulent lineages in patients with chronic ulcers.

Adjusting susceptibilities of C57BL/6 mice to orthoflaviviruses for evaluation of antiviral drugs by altering the levels of interferon alpha/beta receptor function

The purpose of this study was to optimize the infectivity of four different orthoflaviviruses in mice for evaluating antiviral drugs by using wild-type mice with intact interferon responses, type 1 interferon alpha/beta receptor knockout mice, or by injecting wild type C57BL/6 mice with varying doses of anti-type 1 interferon receptor antibody (MAR1-5A3) to optimize the infectivity and lethality. West Nile virus productively infected wild-type C57BL/6 mice to cause lethality, whereas Usutu virus required a complete absence of type 1 interferon receptor function. Deer tick virus (lineage 2 Powassan virus) and Japanese encephalitis viruses required a dampening of type 1 interferon responses by adjusting the doses of MAR1-5A3 antibody injections. Challenge dose-responsive mortality, weight loss, and viral titers of these two viruses were observed if the type 1 interferon responses were dampened with MAR1-5A3. Conversely, without MAR1-5A3 injections, these disease phenotypes were not viral challenge dose-responsive. From these different interferon-responsive models, the appropriate lethality was identified to determine that 7-deaza-2’-C-methyladenosine has high efficacy for West Nile and Usutu viruses, and low efficacy for deer tick and Japanese encephalitis viruses.

Prevalence and Genetic Diversity of Deer Tick Virus (Powassan Virus, Lineage II) in Ixodes scapularis Ticks in Five Habitats at a Nature Reserve in Southern Maine, United States.

Deer tick virus (DTV), also known as Powassan virus lineage II, is a rising health concern due to increased recognition as a cause of human encephalitis. Since European tick-borne encephalitis virus persists in nature in enzootic foci (i.e., higher prevalence rates in small pockets in nature), we sought to determine whether DTV is also focally maintained in relation to habitat type, to better understand factors leading to human risk of exposure. From 2018 to 2021, questing Ixodes scapularis ticks were collected from five habitats at the Wells National Estuarine Research Reserve (WNERR) in Wells, ME: forest with invasive vegetation in the understory, edge, shrub, forest with native vegetation in the understory, and open field. Deer tick virus prevalence was greater in adult ticks (2.0%) than in nymphs (0.5%). Deer tick virus prevalence in adult ticks collected from forest with invasive vegetation was 3.2% compared to 0 to 1.7% in other habitat types. A hot spot analysis revealed a higher number of infected adults collected per hour on one of the transects located in forest with invasive vegetation. Phylogenetic analysis of 37 full-length DTV genomes sequenced in this study revealed four major clades from the WNERR, and there was high genetic diversity within each transect, suggesting frequent, short-range dispersal between habitats. Analysis of DTV sequences from other New England counties and states also indicated long-distance dispersal to and/or from the WNERR. This study provides preliminary evidence that DTV is focal and that the risk of encountering DTV-infected ticks in forest with invasive vegetation may be greater than in other habitat types.

Genomic surveillance reveals a dengue 2 virus epidemic lineage with a marked decrease in sensitivity to Mosnodenvir

Dengue fever is the most important arbovirosis for public health, with more than 5 million cases worldwide in 2023. Mosnodenvir is the first anti-dengue compound with very high preclinical pan-serotype activity, currently undergoing phase 2 clinical evaluation. Here, by analyzing dengue virus (DENV) genomes from the 2023-2024 epidemic in the French Caribbean Islands, we show that they all exhibit mutation NS4B:V91A, previously associated with a marked decrease in sensitivity to mosnodenvir in vitro. Using antiviral activity tests on four clinical and reverse-genetic strains, we confirm a marked decrease in mosnodenvir sensitivity for DENV-2 ( > 1000 fold). Finally, combining phylogenetic analysis and experimental testing for resistance, we find that virus lineages with low sensitivity to mosnodenvir due to the V91A mutation likely emerged multiple times over the last 30 years in DENV-2 and DENV-3. These results call for increased genomic surveillance, in particular to track lineages with resistance mutations. These efforts should allow to better assess the activity profile of DENV treatments in development against circulating strains.