Biology subjects

Bosco-Lauth, A.

Publications and source records attributed to Bosco-Lauth, A..

7 recordsLinked to original sources

bioRxiv2023

Phagocyte-expressed glycosaminoglycans promote capture of alphaviruses from the blood circulation in a host species-specific manner.

The magnitude and duration of vertebrate viremia are critical determinants of arbovirus transmission, geographic spread, and disease severity--yet, mechanisms determining arbovirus viremia levels are poorly defined. Previous studies have drawn associations between in vitro virion-glycosaminoglycan (GAG) interactions and in vivo clearance kinetics of virions from blood circulation. From these observations, it is commonly hypothesized that GAG-binding virions are rapidly removed from circulation due to ubiquitous expression of GAGs by vascular endothelial cells, thereby limiting viremia. Using an in vivo model for viremia, we compared the vascular clearance of low and enhanced GAG-binding viral variants of chikungunya (CHIKV), eastern-(EEEV), and Venezuelan-(VEEV) equine encephalitis viruses. We find GAG-binding virions are more quickly removed from circulation than their non-GAG-binding variant; however individual clearance kinetics vary between GAG-binding viruses, from swift (VEEV) to slow removal from circulation (EEEV). Remarkably, we find phagocytes are required for efficient vascular clearance of some enhanced GAG-binding virions. Moreover, transient depletion of vascular heparan sulfate (HS) impedes vascular clearance of only some GAG-binding viral variants and in a phagocyte-dependent manner, implying phagocytes can mediate vascular GAG-virion interactions. Finally, in direct contrast to mice, we find enhanced GAG-binding EEEV is resistant to vascular clearance in avian hosts, suggesting the existence of species-specificity in virion-GAG interactions. In summary, these data support a role for GAG-mediated clearance of some viral particles from the blood circulation, illuminate the potential of blood-contacting phagocytes as a site for GAG-virion binding, and suggest a role for species-specific GAG structures in arbovirus ecology. Significance StatementPreviously, evidence of arbovirus-GAG interactions in vivo has been limited to associations between viral residues shown to promote enhanced GAG-binding phenotypes in vitro and in vivo phenotypes of viral dissemination and pathogenesis. By directly manipulating host GAG expression, we identified virion-GAG interactions in vivo and discovered a role for phagocyte-expressed GAGs in viral vascular clearance. Moreover, we observe species-specific differences in viral vascular clearance of enhanced GAG-binding virions between murine and avian hosts. These data suggest species-specific variation in GAG structure is a mechanism to distinguish amplifying from dead-end hosts for arbovirus transmission.

microbiology↗

bioRxiv2023

Experimental infection of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) with SARS-CoV-2

Elk (Cervus canadensis) and mule deer (Odocoileus hemionus) were experimentally evaluated for susceptibility to SARS-CoV-2. Elk did not shed infectious virus but produced low-level serological responses. Mule deer shed and transmitted virus in addition to mounting pronounced serological responses; they could therefore play a role in the epidemiology of SARS-CoV-2. Article Summary LineExperimental infection of elk (Cervus canadensis) and mule deer (Odocoileus hemionus) with SARS-CoV-2 revealed that while elk are minimally susceptible to infection, mule deer become infected, shed infectious virus, and can infect naive contacts.

microbiology↗

bioRxiv2023

Intracellular diversity of WNV within circulating avian peripheral blood mononuclear cells reveals host-dependent patterns of polyinfection

Error-prone replication of RNA viruses generates the genetic diversity required for adaptation within rapidly changing environments. Thus, arthropod-borne virus (arbovirus) populations exist in nature as mutant swarms that are maintained between arthropods and vertebrates. Previous studies have demonstrated that West Nile virus (WNV) population dynamics are host dependent: In American crows, which experience extremely high viremia, purifying selection is weak and population diversity is high compared to American robins, which have 100 to 1000-fold lower viremia. WNV passed in robins experiences fitness gains, whereas that passed in crows does not. Therefore, we tested the hypothesis that high crow viremia allows higher genetic diversity within individual avian peripheral-blood mononuclear cells (PBMCs), reasoning that this could have produced the previously observed host-specific differences in genetic diversity and fitness. Specifically, we infected cells and birds with a novel, barcoded version of WNV and sequenced viral RNA from single cells to quantify the number of WNV barcodes that each contained. Our results demonstrate that the richness of WNV populations within crows far exceeds that in robins. Similarly, rare WNV variants were maintained by crows more frequently than by robins. Our results suggest that increased viremia in crows relative to robins leads to maintenance of defective genomes and less prevalent variants, presumably through complementation. Our findings further suggest that weaker purifying selection in highly susceptible crows is attributable to this higher viremia, polyinfections and complementation. These studies further document the role of particular, ecologically relevant hosts in shaping virus population structure. Author SummaryWNV mutational diversity in vertebrates is species-dependent. In crows, low frequency variants are common, and viral populations are more diverse. In robins, fewer mutations become permanent fixtures of the overall viral population. We infected crows, robins and a chicken cell line with a genetically marked (barcoded) WNV. Higher levels of virus led to multiple unique WNV genomes infecting individual cells, even when a genotype was present at low levels in the input viral stock. Our findings suggest that higher levels of circulating virus in natural hosts allow less fit viruses to survive in RNA virus populations through complementation by more fit viruses. This is significant as it allows less represented and less fit viruses to be maintained at low levels until they potentially emerge when virus environments change. Overall our data reveal new insights on the relationships between host susceptibility to high viremia and virus evolution.

microbiology↗

bioRxiv2022

mNGS Investigation of Single Ixodes pacificus Ticks Reveals Diverse Microbes, Viruses, and a Novel mRNA-like Endogenous Viral Elements

Ticks are increasingly important vectors of human and agricultural diseases. While many studies have focused on tick-borne bacteria, far less is known about tick-associated viruses and their roles in public health or tick physiology. To address this, we investigated patterns of bacterial and viral communities across two field populations of western black-legged ticks (Ixodes pacificus). Through metatranscriptomic analysis of 100 individual ticks, we quantified taxon prevalence, abundance, and co-occurrence with other members of the tick microbiome. Our analysis revealed 11 novel RNA viruses from Rhabdoviridae, Chuviridae, Picornaviridae, Phenuiviridae, Reoviridae, Solemovidiae, Narnaviridae, and 2 highly divergent RNA viruses lacking sequence similarity to known viral families. The majority of these viruses were also detectable in lab-raised ticks at all developmental life stages, localize to tick salivary glands, and show evidence of circulation in mice fed on by ticks. These data suggest that viruses are stable, heritable, and transmissible members of the tick microbiota. We also unexpectedly identified numerous virus-like transcripts that are associated with tick genomic DNA, most of which are distinct from known endogenous viral element-mediated immunity pathways in invertebrates. Together, our work reveals that in addition to potentially serving as vectors for potential viral pathogens, I. pacificus ticks may also have symbiotic partnerships with their own vertically-transmitted viruses or with ancient viruses through evolutionarily acquired virus-like transcripts. Our findings highlight how pervasive and intimate tick-virus interactions are, with major implications for both the fundamental physiology and vector biology of I. pacificus ticks.

microbiology↗

bioRxiv2022

Acute Vaping of a golden Syrian Hamster is Feasible and Leads to Nicotine-Dependent Respiratory Tract Inflammation

IntroductionE-cigarette vaping has become a major portion of nicotine consumption, especially for children and young adults. Although it is branded as a safer alternative to cigarette smoking, murine and rat models of sub-acute and chronic e-cigarette vaping exposure have shown many pro-inflammatory changes in the respiratory tract. An acute vaping exposure paradigm has not been demonstrated in the golden Syrian hamster, and the hamster is a readily available small animal model that has the unique benefit of becoming infected with and transmitting SARS-CoV-2 without genetic alteration to the animal or virus. MethodsUsing a two-day, whole-body vaping exposure protocol in male golden Syrian hamsters, we evaluated serum cotinine, bronchoalveolar lavage cells, lung and nasal histopathology, and gene expression in the nasopharynx and lung through RT-qPCR. Depending on the presence of nonnormality or outliers, statistical analysis was performed by ANOVA or Kruskal-Wallis tests. For tests that were statistically significant (p-value <0.05), post-hoc Tukey-Kramer and Dunns tests, respectively, were performed to make pairwise comparisons between groups. ResultsIn nasal tissue, RT-qPCR analysis revealed nicotine-dependent increases in genes associated with type 1 inflammation (CCL-5 and CXCL-10), fibrosis (TGF-{beta}), and a nicotine-independent decrease in the vasculogenesis/angiogenesis gene VEGF-A. In the lung, nicotine-dependent increases in the expression of genes involved in the renin-angiotensin pathway (ACE, ACE2), coagulation (tissue factor, Serpine-1), extracellular matrix remodeling (MMP-2, MMP-9), type 1 inflammation (IL-1{beta}, TNF-, and CXCL-10), fibrosis (TGF-{beta} and Serpine-1), oxidative stress response (SOD-2), neutrophil extracellular traps release (ELANE), and vasculogenesis and angiogenesis (VEGF-A) were identified. ConclusionTo our knowledge, this is the first demonstration that the Syrian hamster is a viable model of e-cig induced inhalational injury. In addition, this is the first report that e-cig vaping with nicotine can increase tissue factor gene expression in the lung. Our results show that even an acute exposure to e-cigarette vaping causes significant upregulation in the respiratory tract of pathways involving the renin-angiotensin system, coagulation, extracellular matrix remodeling, type 1 inflammation, fibrosis, oxidative stress response, NETosis, vasculogenesis, and angiogenesis.

pharmacology and toxicology↗

bioRxiv2021

SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection

SARS-CoV-2 spillback from humans into domestic and wild animals has been well-documented. We compared variants of cell culture-expanded SARS-CoV-2 inoculum and virus recovered from four species following experimental exposure. Five nonsynonymous changes in nsp12, S, N and M genes were near fixation in the inoculum, but reverted to wild-type sequences in RNA recovered from dogs, cats and hamsters within 1-3 days post-exposure. Fourteen emergent variants were detected in viruses recovered from animals, including substitutions at spike positions H69, N501, and D614, which also vary in human lineages of concern. The rapidity of in vitro and in vivo SARS-CoV-2 selection reveals residues with functional significance during host-switching, illustrating the potential for spillback reservoir hosts to accelerate evolution, and demonstrating plasticity of viral adaptation in animal models. One-Sentence SummarySARS-CoV-2 variants rapidly arise in non-human hosts, revealing viral evolution and potential risk for human reinfection.

evolutionary biology↗

bioRxiv2021

Survey of peridomestic mammal susceptibility to SARS-CoV-2 infection

Wild animals have been implicated as the origin of SARS-CoV-2, but it is largely unknown how the virus affects most wildlife species and if wildlife could ultimately serve as a reservoir for maintaining the virus outside the human population. Here we show that several common peridomestic species, including deer mice, bushy-tailed woodrats, and striped skunks, are susceptible to infection and can shed the virus in respiratory secretions. In contrast, we demonstrate that cottontail rabbits, fox squirrels, Wyoming ground squirrels, black-tailed prairie dogs, house mice, and racoons are not susceptible to SARS-CoV-2 infection. Our work expands upon the existing knowledge base of susceptible species and provides evidence that human-wildlife interactions could result in continued transmission of SARS-CoV-2.

microbiology↗