Biology subjects

Dupuis, A. P.

Publications and source records attributed to Dupuis, A. P..

7 recordsLinked to original sources

bioRxiv2026

Species-specific susceptibility and low transmission of the historical Japanese encephalitis virus Nakayama strain in North American Culex mosquitoes

Japanese encephalitis virus (JEV) is an emerging mosquito-borne flavivirus with potential for geographic expansion, yet the risk of establishment in North America remains poorly characterized. We assessed vector competence of three North American Culex species (Cx. pipiens, Cx. quinquefasciatus, and Cx. tarsalis) for the JEV Nakayama strain, isolated from human brain in 1934 in Japan, across five constant temperatures (15, 20, 25, 30, and 33{degrees}C) at 4, 7, and 14 days post-feeding, quantifying infection, dissemination, and transmission rates. Vector competence was low but non-zero across all species. Cx. pipiens showed higher infection rates than the other species, whereas Cx. quinquefasciatus and Cx. tarsalis were minimally susceptible under these experimental conditions. Temperature had limited effects on infection and no detectable effects on dissemination or transmission. These findings suggest limited transmission potential of JEV Nakayama in North America, with Cx. pipiens as a relatively permissive vector.

molecular biology↗

bioRxiv2026

Evolutionary history of Jamestown Canyon virus disentangles complex multi-vector ecology

Jamestown Canyon virus (JCV) is a re-emerging mosquito-borne virus of increasing concern in North America. It has been historically understudied, leading to significant gaps in our understanding of its evolutionary history, ecological maintenance, and transmission dynamics. Here, we generated 658 whole-genome JCV sequences from the Northeast United States, including 84% (500/597) of all JCV-positive mosquitoes detected in Connecticut from 1997-2022. Then we applied phylodynamic methods to demonstrate how mosquito phenology and host interaction structure the persistence and spread of JCV. Our phylogenetic analyses estimate that JCV was introduced in the Northeast by at least the early 1700s and the primary introductions of lineages A and B into Connecticut occurred during the mid-1800s to mid-1900s. Further, we estimate that JCV evolves at a rate of [~]3 x 10-5 s/s/y, making it one of the slowest evolving known RNA viruses, because the virus spends [~]10 months per year in evolutionary stasis while over-wintering in mosquito eggs. To investigate ecological drivers of JCV spread in Connecticut, we paired discrete trait and continuous phylogeographic reconstructions with mosquito surveillance data. We estimate that JCV has a low diffusion rate of [~]30-60 km2/year, which is more similar to slow-moving tick-borne viruses than other mosquito-borne viruses. We found that univoltine Aedes mosquitoes were likely to maintain the virus across years through overwintering in eggs, accounting for its slow evolution and dispersal, while multivoltine mosquitoes contribute to periodic bursts of spatial diffusion and amplification within seasons. By characterizing seasonal dynamics of JCV, we demonstrate the utility of dense sequencing and phylodynamics to disentangle complex transmission cycles, offering a framework to rapidly advance our evolutionary and ecological knowledge of understudied viruses.

ecology↗

bioRxiv2022

Phylogeographic reconstruction of the emergence and spread of Powassan virus in the northeastern United States

Powassan virus is an emerging tick-borne virus of concern for public health, but very little is known about its transmission patterns and ecology. Here, we expanded the genomic dataset by sequencing 279 Powassan viruses isolated from Ixodes scapularis ticks from the northeastern United States. Our phylogeographic reconstructions revealed that Powassan virus lineage II was likely introduced or emerged from a relict population in the Northeast between 1940-1975. Sequences strongly clustered by sampling location, suggesting a highly focal geographical distribution. Our analyses further indicated that Powassan virus lineage II emerged in the northeastern U.S. mostly following a south to north pattern, with a weighted lineage dispersal velocity of ~3 km/year. Since the emergence in the Northeast, we found an overall increase in the effective population size of Powassan virus lineage II, but with growth stagnating during recent years. The cascading effect of population expansion of white-tailed deer and I. scapularis populations likely facilitated the emergence of Powassan virus in the northeastern U.S. Significance statementOur work provides important fundamental insights in the local transmission dynamics of an emerging tick-borne pathogen of public health concern. Without the availability of vaccines or specific treatments, prevention of Powassan virus infection is dependent on education and control. We identified that Powassan virus is maintained in highly localized transmission foci that have been maintained for several years, without introductions of new virus clades. This provides both opportunities for better education about high risk areas and effective targeted control in Powassan virus foci with a long lasting impact.

genomics↗

bioRxiv2022

Structural evolution of an immune evasion determinant shapes Lyme borreliae host tropism

The preferential adaptation of pathogens to specific hosts, known as host tropism, evolves through host-pathogen interactions. Transmitted by ticks and maintained primarily in rodents and birds, the Lyme disease-causing bacterium Borrelia burgdorferi (Bb) is an ideal model to investigate the mechanisms of host tropism. In order to survive in hosts and escape complement-mediated clearance, a first-line host immune defense, Bb produces the outer surface protein CspZ that binds to the complement inhibitor factor H (FH) to facilitate bacterial dissemination in vertebrates. Despite high sequence conservation, CspZ variants vary in human FH-binding ability. Together with the FH polymorphisms found amongst vertebrate hosts, these findings raise a hypothesis that minor sequence variation in a bacterial outer surface protein confers dramatic differences in host- specific, FH-binding-mediated infectivity. We tested this hypothesis by determining the crystal structure of the CspZ-human FH complex, identifying a minor change localized in the FH-binding interface, and uncovered that the bird and rodent FH-specific binding activity of different CspZ variants directly impacts infectivity. Swapping the divergent loop region in the FH-binding interface between rodent- and bird-associated CspZ variants alters the ability to promote rodent- and bird-specific early-onset dissemination. By employing phylogenetic tree thinking, we correlated these loops and respective host-specific, complement-dependent phenotypes with distinct CspZ lineages and elucidated evolutionary mechanisms driving CspZ emergence. Our multidisciplinary work provides mechanistic insights into how a single, short pathogen protein motif could greatly impact host tropism. AUTHOR SUMMARYLyme disease presents a suitable model for the investigation of host tropism - a pathogens ability to colonize and survive in different host species - since its causative agent, the spirochete Borrelia burgdorferi (Bb) is transmitted by ticks and maintained in rodent and bird reservoir hosts. In order to survive in vertebrates and escape from killing by complement, a first-line host immune defense, Bb produces the outer surface protein CspZ that binds the complement inhibitor factor H (FH) to promote infection. Protein sequence conservation seems to be linked to FH-binding activity divergence, raising the hypothesis that even minor variation can confer host-specific, FH- binding-mediated infectivity. Our work shows that that this minor variation is located in a loop in the CspZ protein localized in the CspZ-FH binding interface. Our functional experiments prove that this loop promotes bird- or rodent-specific FH-binding activity and infectivity. Swapping loops between rodent- and bird-associated CspZ variants alters their capability to confer host- specific dissemination. We further investigated the evolutionary mechanisms driving the emergence of the CspZ loop-mediated, host-dependent complement evasion. This multifaceted work demonstrates how a single, short protein motif can significantly impact host tropism.

microbiology↗

bioRxiv2022

Phylogenomic diversity elucidates mechanistic insights into Lyme borreliae host association

Host association- the selective adaptation of pathogens to specific host species - evolves through constant interactions between host and pathogens, leaving a lot yet to be discovered on immunological mechanisms and genomic determinants. The causative agents of Lyme disease (LD) are spirochete bacteria composed of multiple species of the Borrelia burgdorferi sensu lato complex, including B. burgdorferi (Bb), the main LD pathogen in North America - a useful model for the study of mechanisms underlying host-pathogen association. Host adaptation requires pathogens ability to evade host immune responses, such as complement, the first-line innate immune defense mechanism. We tested the hypothesis that different host adapted phenotypes among Bb strains are linked to polymorphic loci that confer complement evasion traits in a host-specific manner. We first examined the survivability of 20 Bb strains in sera in vitro and/or bloodstream and tissues in vivo from rodent and avian LD models. Three groups of complement-dependent host association phenotypes emerged. We analyzed complement-evasion genes, identified a priori among all strains and sequenced and compared genomes for individual strains representing each phenotype. The evolutionary history of ospC loci is correlated with host-specific complement-evasion phenotypes, while comparative genomics suggests several gene families and loci are potentially involved in host association. This multidisciplinary work provides novel insights into the functional evolution of host adapted phenotypes, building a foundation for further investigation of the immunological and genomic determinants of host association. IMPORTANCEHost association is the phenotype that is commonly found in many pathogens that preferential survive in particular hosts. The Lyme disease (LD) causing agent, B. burgdorferi (Bb), is an ideal model to study host association, as Bb is mainly maintained in nature through rodent and avian hosts. A widespread yet untested concept posits that host association in Bb strains is linked to Bb functional genetic variation conferring evasion to complement, an innate defense mechanism in vertebrate sera. Here, we tested this concept by grouping 20 Bb strains into three complement-dependent host association phenotypes based on their survivability in sera and/or bloodstream and distal tissues in rodent and avian LD models. Phylogenomic analysis of these strains further correlated several gene families and loci, including ospC, with host-specific complement-evasion phenotypes. Such multifaceted studies thus pave the road to further identify the determinants of host association, providing mechanistic insights into host-pathogen interaction.

microbiology↗

bioRxiv2021

Host tropism determination by convergent evolution of immunological evasion in the Lyme disease system

Microparasites selectively adapt in some hosts, known as host tropism. Transmitted through ticks and carried mainly by mammals and birds, the Lyme disease (LD) bacterium is a well-suited model to study such tropism. LD bacteria species vary in host ranges through mechanisms eluding characterization. By feeding ticks infected with different LD bacteria species, utilizing feeding chambers and live mice and quail, we found species-level differences of bacterial transmission. These differences localize on the tick blood meal, and complement, a defense in vertebrate blood, and a bacterial polymorphic protein, CspA, which inactivates complement by binding to a host complement inhibitor, FH. CspA selectively confers bacterial transmission to vertebrates that produce FH capable of allele-specific recognition. Phylogenetic analyses revealed convergent evolution as the driver of such findings, which likely emerged during the last glacial maximum. Our results identify LD bacterial determinants of host tropism, defining an evolutionary mechanism that shapes host-microparasite associations.

microbiology↗

bioRxiv2020

Cellular and immunological mechanisms mediate reservoir host specialization by genotypically variable microparasites

Host specialization is an ecological and evolutionary process by which a pathogen becomes differentially adapted to a subset of hosts, restricting its host range. For parasites transmitted by generalist vectors, host specialization is not expected to evolve because of the decreased survival of those parasites in inadequate hosts. Thus, parasites may develop adaptation strategies, resulting in host specialization. The causative agents of Lyme disease are multiple species of bacteria, Borrelia burgdorferi sensu lato species complex (Bbsl), and are suitable for examining host specialization as birds and rodents were found to carry different species of these bacteria. Debate exists on whether host specialization occurs among these strains within a particular species of Bbsl, such as B. burgdorferi sensu stricto (Bbss). Current evidence supports some Bbss strains are widespread in white-footed mice but others are in non-rodent vertebrates, such as birds. To recapitulate specialization in the laboratory and define the mechanisms for host specialization, we introduced different genotypes of Bbss via tick transmission to American robins and white-footed mice, the Lyme disease reservoirs in North America. Among these strains, we found distinct levels of spirochete presence in the bloodstream and tissues and maintenance by these animals in a host-dependent fashion. We showed that the late stage persistence of these strains largely corresponds to bacterial survival at early infection onsets. We also demonstrated that those early survival phenotypes correspond to spirochete adhesiveness, evasion of complement-mediated killing in sera, and/or not triggering high levels of pro-inflammatory cytokines and antibodies. Our findings thus link host competence to Bbss with spirochete genotypic variation of adhesiveness and inducing/escaping host immune responses, illuminating the potential mechanisms that dictate host specialization. Such information will provide a foundation for further investigation into multi-disciplinary processes driving host specialization of microparasites. AUTHOR SUMMARYHost specialization arises when microparasites adapt to a subset of available hosts, restricting the host ranges they can infect. The mechanisms and selective pressures for the evolution of host specialization remain unclear. The causative agent of Lyme disease (LD), the bacteria species complex of Borrelia burgdorferi sensu lato, is adapted to different vertebrates. However, whether such a differential host adaption also applies to each genotype within the same species is under debate. Further, the mechanisms that drive such host specialization are unclear. We thus introduced three genotypes of one LD bacteria species (B. burgdorferi sensu stricto) individually via tick bite to American robins and white-footed mice, the most common LD reservoirs in North America. We found that these genotypes differed in the persistent maintenance by those reservoirs and occurred in a host-specific fashion. The ability of those bacteria for long-term maintenance was linked with their capability to attach to cells and a lack of induction of high levels of immune responses at early infection onsets. This work demonstrates the potential mechanisms that dictate host specialization of LD bacteria circulating in natural populations. Such information will pave the road to define the molecular, ecological, and evolutionary determinants that drive host-microparasite interactions.

microbiology↗