Biology subjects

Kraberger, S.

Publications and source records attributed to Kraberger, S..

12 recordsLinked to original sources

bioRxiv2026

Insights from a mobile healthcare clinic in Madagascar: Diversity and dynamics of viruses from febrile individuals in rural subsistence communities

Communities living in biodiversity hotspots are at increased risk of pathogen exposure and spread due to insufficient access to nutrition, clean water, and sanitation. Viruses, in particular, have high epidemic and spillover potential, and widespread health impacts, yet, viral diversity and dynamics remain understudied in many high-risk regions. In Madagascar, a hotspot with unparalleled biodiversity, socioeconomic constraints, and a heavy burden of infectious diseases, ongoing healthcare initiatives provide opportunities to survey circulating viral diversity. Here, we used a metagenomic workflow to characterize the viromes of oral/nasal swabs from febrile individuals visiting a mobile healthcare clinic in southeastern Madagascar, of which 49% were malaria-positive (Plasmodium falciparum). We characterized sequences of human-infecting viruses from twelve families (Adenoviridae, Anelloviridae, Orthoherpesviridae, Papillomaviridae, Polyomaviridae, Astroviridae, Coronaviridae, Matonaviridae, Orthomyxoviridae, Paramyxoviridae, Picornaviridae, and Sedoreoviridae). These viral sequences generally showed high similarity to known lineages circulating globally, but multiple viruses considered rare or emerging were identified (e.g. enterovirus C105, enterovirus C117). While we did not detect a significant association between malaria status and pathogenic virus presence, younger individuals had higher odds of having a pathogenic virus. Nonpathogenic viruses in Anelloviridae were prevalent and diverse with richness ranging from 0 to 70. Individuals with P. falciparum or a pathogenic virus tended to share more anelloviruses. We also detected viruses that are protist-associated, plant-infecting, or with unknown hosts. Overall, our work documents extensive viral diversity in Madagascar, highlighting how metagenomic workflows can be used to build viral genomic resources for pathogen surveillance in regions with high infectious disease burden.

microbiology↗

bioRxiv2026

Atypical myxomatosis in European rabbits is caused by the recombinant myxoma virus involved in species jumping into hares

Myxoma virus (MYXV), a member of the Leporipoxvirus genus (species Leporipoxvirus myxoma; family Poxviridae), causes a highly lethal disease known as myxomatosis in European rabbits. In late 2018, a new natural MYXV isolate, MYXV-Tol (a.k.a. hare MYXV; ha-MYXV), emerged and caused myxomatosis-like disease with high mortality in Iberian hares, European brown hares, and European rabbits. This variant contains an approximately 2.8-kb insertion of a recombination cassette within the M009L gene encoding four additional genes, including the C7-like host range gene, M159L. M159 is essential for replication of MYXV-Tol in hare cells and is likely a key determinant of its pathogenicity in both hares and rabbits. Here, we compared the pathogenicity of wild-type MYXV-Tol (vMyx-Tol), an M159 deletion strain (vMyx-Tol-M159KO), and the classical MYXV-Lau strain (vMyx-Lau) in European rabbits. All three viruses caused systemic disease; however, vMyx-Tol and vMyx-Tol-M159KO produced clinical signs distinct from classical myxomatosis. Infection with vMyx-Tol and vMyx-Tol-M159KO was characterized by the absence of the typical primary and secondary nodular lesions, and caused severe edema, marked fluid accumulation, lymphocyte infection, and significantly reduced or no virus-neutralizing antibody responses. The disease caused by both vMyx-Tol and vMyx-Tol-M159KO progressed rapidly within 9-11 days, resulting in animals reaching humane euthanasia endpoints like vMyx-Lau. Deletion of M159 did not significantly alter MYXV-Tol pathogenicity in rabbits. Collectively, these findings demonstrate that MYXV-Tol has evolved to cause an atypical, amyxomatous-like acute to hyperacute disease in European rabbits and likely in hares. SignificanceNatural evolution enables viruses to cross species barriers and adapt to new hosts. Myxoma virus (MYXV), released in the 1950s in Australia and Europe as a biocontrol agent against European rabbits, became a classic model for real-time monitoring of virus evolution, virulence, and host adaptation. Although MYXV is typically host-restricted, a newly emerged natural isolate, MYXV-Tol, causes lethal disease in both hares and rabbits. Here, we show that MYXV-Tol induces an atypical, amyxomatous-like disease characterized by the absence of nodular lesions, severe edema, lymphocyte infection, and markedly reduced virus-neutralizing antibody responses. These findings reveal previously unrecognized virus-host interactions that shape disease outcome and provide new insight into the mechanisms driving viral adaptation and evolution.

microbiology↗

bioRxiv2022

African army ants at the forefront of virome surveillance in a remote tropical forest

In this study, we used a predator-enabled metagenomics strategy to sample the virome of a remote and difficult-to-access densely forested African tropical region. Specifically, we focused our study on the use of army ants of the genus Dorylus that are obligate collective foragers and group predators that attack and overwhelm a broad array of animal prey. Using 209 army ant samples collected from 29 colonies and the virion-associated nucleic acid-based metagenomics approach, we showed that a broad diversity of bacterial, plant, invertebrate and vertebrate viral sequences were accumulated by army ants: including sequences from 157 different viral genera in 56 viral families. This suggests that using predators and scavengers such as army ants to sample broad swathes of tropical forest viromes can shed light on the composition and the structure of viral populations of these complex and inaccessible ecosystems.

microbiology↗

bioRxiv2022

Treatment with anti-inflammatory viral serpin modulates immuno-thrombotic responses and improves outcomes in SARS-CoV-2 infected mice

1.Severe acute respiratory distress syndrome (ARDS) during SARS-CoV-2 (severe acute respiratory syndrome coronavirus-2) infection, manifests as uncontrolled lung inflammation and systemic thrombosis with high mortality. Anti-viral drugs and monoclonal antibodies can reduce COVID-19 severity if administered in the early viremic phase, but treatments for later stage immuno-thrombotic syndrome and long COVID are limited. Serine protease inhibitors (SERPINS) regulate activated proteases during thrombotic, thrombolytic and immune responses. The myxoma poxvirus-derived Serp-1 protein is a secreted immunomodulatory serpin that targets activated coagulation and complement protease pathways as part of a self-defense strategy to combat viral clearance by the innate immune system. When purified and utilized as an anti-immune therapeutic, Serp-1 is effective as an anti-inflammatory drug in multiple animal models of inflammatory lung disease and vasculitis. Here, we describe systemic treatment with purified PEGylated Serp-1 (PEGSerp-1) as a therapy for immuno-thrombotic complications during ARDS. Treatment with PEGSerp-1 in two distinct mouse-adapted SARS-CoV-2 models in C57Bl/6 and BALB/c mice reduced lung and heart inflammation, with improved clinical outcomes. PEGSerp-1 significantly reduced M1 macrophage invasion in the lung and heart by modifying urokinase-type plasminogen activator receptor (uPAR) and complement membrane attack complex (MAC). Sequential changes in urokinase-type plasminogen activator receptor (uPAR) and serpin gene expression were observed in lung and heart with PEGSerp-1 treatment. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for treatment of severe viral ARDS with additional potential to reduce late SARS-CoV-2 complications related to immune-thrombotic events that persist during long COVID. SignificanceSevere acute respiratory distress syndrome (ARDS) in SARS-CoV-2 infection manifests as uncontrolled tissue inflammation and systemic thrombosis with high mortality. Anti-viral drugs and monoclonal antibodies reduce COVID-19 severity if administered early, but treatments for later stage immuno-thrombosis are limited. Serine protease inhibitors (SERPINS) regulate thrombotic, thrombolytic and complement pathways. We investigate here systemic treatment with purified poxvirus-derived PEGSerp-1 as a therapeutic for immuno-thrombotic complications in viral ARDS. PEGSerp-1 treatment in two mouse-adapted SARS-CoV-2 models (C57Bl/6 and BALB/c) significantly reduced lung and heart inflammation and improved clinical outcomes, with sequential changes in thrombolytic (uPAR) and complement expression. PEGSerp-1 is a highly effective immune-modulator with therapeutic potential for immune-thrombotic complications in severe viral ARDS and has potential benefit for long COVID.

microbiology↗

bioRxiv2021

A novel lineage of polyomaviruses identified in bark scorpions

Polyomaviruses are non-enveloped viruses with circular double-stranded DNA genomes that range in size from [~]4-7 kilobasepairs. Initially identified in mammals, polyomaviruses have now been identified in birds and a few fish species. Although fragmentary polyomavirus-like sequences have been detected as apparent hitchhikers in shotgun genomics datasets for various arthropods, the possible diversity of these viruses in invertebrates remains unclear. In general, polyomaviruses are host-specific, showing strong evidence of host-virus co-evolution. Identification of polyomaviruses in a broader range of animals could shed useful light on the evolutionary history of this medically important group of viruses. Scorpions are predatory arachnids that are among the oldest terrestrial animals. Thus far, viromes of arachnids have been under-sampled and understudied. Here, high-throughput sequencing and traditional molecular techniques were used to explore the diversity of circular DNA viruses associated with bark scorpions (Centruroides sculpturatus) from the greater Phoenix area, Arizona, USA. The complete genomes of eight novel polyomaviruses were identified. Analysis of Centruroides transcriptomic datasets elucidated the splicing of the viral late gene array, which is more complex than that of vertebrate polyomaviruses. Phylogenetic analysis provides further evidence of co-divergence of polyomaviruses with their hosts, suggesting that at least one ancestral species of polyomaviruses was circulating amongst the primitive common ancestors of arthropods and chordates.

microbiology↗

bioRxiv2021

Co-evolutionary analysis suggests a role for TLR9 in papillomavirus restriction

A.Upon infection, DNA viruses can be sensed by pattern recognition receptors (PRRs) leading to the activation of type I and III interferons, aimed at blocking infection. Therefore, viruses must inhibit these signaling pathways, avoid being detected, or both. Papillomavirus virions are trafficked from early endosomes to the Golgi apparatus and wait for the onset of mitosis to complete nuclear entry. This unique subcellular trafficking strategy avoids detection by cytoplasmic PRRs, a property that may contribute to establishment of infection. However, as the capsid uncoats within acidic endosomal compartments, the viral DNA may be exposed to detection by toll-like receptor (TLR) 9. In this study we characterize two new papillomaviruses from bats and use molecular archeology to demonstrate that their genomes altered their nucleotide composition to avoid detection by TLR9, providing evidence that TLR9 acts as a PRR during papillomavirus infection. Furthermore, we demonstrate that TLR9, like other components of the innate immune system, is under evolutionary selection in bats, providing the first direct evidence for co-evolution between papillomaviruses and their hosts.

microbiology↗

bioRxiv2021

Feline leukemia virus (FeLV) endogenous and exogenous recombination events result in multiple FeLV-B subtypes during natural infection

Feline leukemia virus (FeLV) is associated with a range of clinical signs in felid species. The primary hosts of FeLV are domestic cats of the Felis genus that also harbor endogenous FeLV (enFeLV) elements stably integrated in their genomes. EnFeLV elements display 86% nucleotide identity to exogenous, horizontally transmitted FeLV (FeLV-A). Variation between enFeLV and FeLV-A is primarily in the long terminal repeat (LTR) and env regions, which potentiates generation of FeLV-B recombinant subtypes during natural infection with enhanced virulence. The aim of this study was to examine exogenous FeLV (exFeLV) and enFeLV recombination events in a natural FeLV epizootic. We previously described that of 32 individuals in a closed colony with productive FeLV-A infection, 22 had detectable circulating FeLV-B. We cloned and sequenced the env gene of FeLV-B, FeLV-A, and enFeLV spanning known recombination breakpoints, examining between 1-13 clones per individual to assess sequence diversity and recombination sites. We documented multiple recombination breakpoints resulting in the production of unique FeLV-B genotypes. At least half of the cats harbored more than one FeLV-B variant, and almost all animals had variants similar to those recovered from at least one other individual in the colony. This analysis reveals that FeLV-B is predominantly generated de novo within each host, though horizontal transmission may be inferred based upon FeLV-B sequence identities between individuals. This work represents a comprehensive analysis of endogenous-exogenous retroviral interactions with important insights into host-viral interactions that underlie disease pathogenesis in a natural setting. ImportanceFeline leukemia virus (FeLV) is a felid retrovirus associated with a variety of disease outcomes. Exogenous FeLV-A is the most common horizontally transmitted virus subgroup. Domestic cats (Felis catus) harbor endogenous copies of FeLV (enFeLV) in their genomes. Recombination between FeLV-A and enFeLV may result in emergence of largely replication-defective, but highly virulent recombinant strains. FeLV-B, the most common recombinant form, results when enFeLV env recombines with FeLV-A during FeLV replication. This study evaluated endogenous-exogenous recombination outcomes in a naturally-infected closed colony of domestic cats to determine recombination sites and FeLV-B genotypic heterogeneity associated with enhanced disease virulence. While FeLV-A and enFeLV genotypes were highly conserved, a large number of unique FeLV-B variants were identified in association with predicted recombination hotspots. The findings provide insight into recombination events between viral and host genomes that result in new, and potentially more pathogenic, viral strains.

microbiology↗

bioRxiv2021

Transmission of one predicts another: Apathogenic proxies for transmission dynamics of a fatal virus

Identifying drivers of transmission prior to an epidemic--especially of an emerging pathogen--is a formidable challenge for proactive disease management efforts. We tested a novel approach in the Florida panther, hypothesizing that apathogenic feline immunodeficiency virus (FIV) transmission could predict transmission dynamics for pathogenic feline leukemia virus (FeLV). We derived a transmission network using FIV whole genome sequences, and used exponential random graph models to determine drivers structuring this network. We used these drivers to predict FeLV transmission pathways among panthers and compared predicted outbreak dynamics against empirical FeLV outbreak data. FIV transmission was primarily driven by panther age class and distances between panther home range centroids. Prospective FIV-based modeling predicted FeLV dynamics at least as well as simpler, often retrospective approaches, with evidence that FIV-based predictions captured the spatial structuring of the observed FeLV outbreak. Our finding that an apathogenic agent can predict transmission of an analogously transmitted pathogen is an innovative approach that warrants testing in other host-pathogen systems to determine generalizability. Use of such apathogenic agents holds promise for improving predictions of pathogen transmission in novel host populations, and could thereby provide new strategies for proactive pathogen management in human and animal systems.

ecology↗

bioRxiv2020

Unveiling Crucivirus Diversity by Mining Metagenomic Data

The discovery of cruciviruses revealed the most explicit example of a common protein homologue between DNA and RNA viruses to date. Cruciviruses are a novel group of circular Rep-encoding ssDNA (CRESS-DNA) viruses that encode capsid proteins (CPs) that are most closely related to those encoded by RNA viruses in the family Tombusviridae. The apparent chimeric nature of the two core proteins encoded by crucivirus genomes suggests horizontal gene transfer of CP genes between DNA and RNA viruses. Here, we identified and characterized 451 new crucivirus genomes and ten CP-encoding circular genetic elements through de novo assembly and mining of metagenomic data. These genomes are highly diverse, as demonstrated by sequence comparisons and phylogenetic analysis of subsets of the protein sequences they encode. Most of the variation is reflected in the replication associated protein (Rep) sequences, and much of the sequence diversity appears to be due to recombination. Our results suggest that recombination tends to occur more frequently among groups of cruciviruses with relatively similar capsid proteins, and that the exchange of Rep protein domains between cruciviruses is rarer than gene exchange. Altogether, we provide a comprehensive and descriptive characterization of cruciviruses. IMPORTANCEViruses are the most abundant biological entities on Earth. In addition to their impact on animal and plant health, viruses have important roles in ecosystem dynamics as well as in the evolution of the biosphere. Circular Rep-encoding single-stranded (CRESS) DNA viruses are ubiquitous in nature, many are agriculturally important, and are viruses that appear to have multiple origins from prokaryotic plasmids. CRESS-DNA viruses such as the cruciviruses, have homologues of capsid proteins (CPs) encoded by RNA viruses. The genetic structure of cruciviruses attests to the transfer of capsid genes between disparate groups of viruses. However, the evolutionary history of cruciviruses is still unclear. By collecting and analyzing cruciviral sequence data, we provide a deeper insight into the evolutionary intricacies of cruciviruses. Our results reveal an unexpected diversity of this virus group, with frequent recombination as an important determinant of variability.

evolutionary biology↗

bioRxiv2019

Host relatedness and landscape connectivity shape pathogen spread in a large secretive carnivore

Urban expansion can fundamentally alter wildlife movement and gene flow, but how urbanization alters pathogen spread is poorly understood. Here we combine high resolution host and viral genomic data with landscape variables to examine the context of viral spread in puma from two contrasting regions: one bounded by the wildland urban interface (WUI) and one unbounded with minimal anthropogenic development. We found landscape variables and host gene flow explained significant amounts of variation of feline immunodeficiency virus (FIV) spread in the WUI, but not in the unbounded region. The most important predictors of viral spread also differed; host spatial proximity, host relatedness, and mountain ranges played a role in FIV spread in the WUI, whereas unpaved roads were more important in the unbounded region. Our research demonstrates how anthropogenic landscapes can alter pathogen spread, providing a more nuanced understanding of host-pathogen relationships to inform disease ecology in free-ranging species.

ecology↗

bioRxiv2019

Urbanization impacts apex predator gene flow but not genetic diversity across an urban-rural divide

Apex predators are important indicators of intact natural ecosystems. They are also sensitive to urbanization because they require broad home ranges and extensive contiguous habitat to support their prey base. Pumas (Puma concolor) can persist near human developed areas, but urbanization may be detrimental to their movement ecology, population structure, and genetic diversity. To investigate potential effects of urbanization in population connectivity of pumas, we performed a landscape genomics study of 134 pumas on the rural Western Slope and more urbanized Front Range of Colorado, USA. Over 12,000 single nucleotide polymorphisms were genotyped using double-digest, restriction site-associated DNA sequencing (ddRADseq). We investigated patterns of gene flow and genetic diversity, and tested for correlations between key landscape variables and genetic distance to assess the effects of urbanization and other landscape factors on gene flow. Levels of genetic diversity were similar for the Western Slope and Front Range, but effective population sizes were smaller, genetic distances were higher, and there was more overall population substructure in the more urbanized Front Range. Forest cover was strongly positively associated with puma gene flow on the Western Slope, while impervious surfaces restricted gene flow and more open, natural habitats enhanced gene flow on the Front Range. Landscape genomic analyses revealed differences in puma movement and gene flow patterns in rural versus urban settings. Our results highlight the utility of dense, genome-scale markers to document subtle impacts of urbanization on a wide-ranging carnivore living near a large urban center.

genomics↗

bioRxiv2019

Genetic characterization of a recombinant myxoma virus leap into the Iberian hare (Lepus granatensis)

Myxomatosis is a lethal disease of wild European and domestic rabbits (Oryctolagus cuniculus) caused by a Myxoma virus (MYXV) infection, a leporipoxvirus that is found naturally in some Sylvilagus rabbit species in South America and California. The introduction of MYXV in the early 1950s into feral European rabbit populations in Australia and Europe demonstrate the best documented field example of host-virus coevolution following a cross-species transmission. Recently, a new cross-species jump of MYXV has been suggested in both Great Britain and Spain, where European brown hares (Lepus europaeus) and Iberian hares (Lepus granatensis) were found dead with lesions consistent with those observed in myxomatosis. To investigate the possibility of a new cross-species transmission event by MYXV, tissue samples collected from a wild Iberian hare found dead in Spain (Toledo region) were analyzed and deep sequenced. Our results report a new MYXV strain (MYXV Toledo) in the tissues of this species. The genome of this new strain encodes three disrupted genes (M009L, M036L and M152R) and a novel 2.8 KB recombinant region that resulted from an insertion of four novel poxviral genes towards the 5 end of its genome. From the open reading frames inserted into the MYXV Toledo strain, a new orthologue of a poxvirus host range gene family member was identified which is related to the MYXV gene M064R. Overall, we confirmed the identity of a new MYXV strain in Iberian hares that we hypothesize was able to more effectively counteract the host defenses in hares and start an infectious process in this new host.

microbiology↗