scholarly journals Rapid dissemination and monopolization of viral populations in mice revealed using a panel of barcoded viruses

2019 ◽  
Author(s):  
Broc T. McCune ◽  
Matthew R. Lanahan ◽  
Benjamin R. tenOever ◽  
Julie K. Pfeiffer
Keyword(s):  
Population Dynamics ◽  
Gastrointestinal Tract ◽  
Enteric Virus ◽  
Population Diversity ◽  
Viral Population ◽  
Post Inoculation ◽  
Systemic Dissemination ◽  
Mouse Tissues ◽  
Oral Inoculation ◽  
Rapid Dissemination

AbstractThe gastrointestinal tract presents a formidable barrier for pathogens to initiate infection. Despite this barrier, enteroviruses, including coxsackievirus B3 (CVB3), successfully penetrate the intestine to initiate infection and spread systemically prior to shedding in stool. However, the effect of the gastrointestinal barrier on CVB3 population dynamics is relatively unexplored, nor are the selective pressures acting on CVB3 in the intestine well-characterized. To examine viral population dynamics in orally infected mice, we produced over one hundred CVB3 viruses harboring unique nine nucleotide “barcodes.” Using this collection of barcoded viruses, we found diverse viral populations throughout each mouse within the first day post-infection, but by 48 hours the viral populations were dominated by less than three barcoded viruses in intestinal and extra-intestinal tissues. Using light-sensitive viruses to track replication status, we found diverse viruses had replicated prior to loss of diversity. Sequencing whole viral genomes from samples later in infection did not reveal detectable viral adaptations. Surprisingly, orally inoculated CVB3 was detectable in pancreas and liver as soon as 20 minutes post inoculation, indicating rapid systemic dissemination. These results suggest rapid dissemination of diverse viral populations, followed by a major restriction in population diversity and monopolization in all examined tissues. These results underscore a complex dynamic between dissemination and clearance for an enteric virus.ImportanceEnteric viruses initiate infection in the gastrointestinal tract but can disseminate to systemic sites. However, the dynamics of viral dissemination are unclear. In this study, we created a library of 135 barcoded coxsackieviruses to examine viral population diversity across time and space following oral inoculation of mice. Overall, we found that the broad population of viruses disseminates early, followed by monopolization of mouse tissues with three or fewer pool members at later time points. Interestingly, we detected virus in systemic tissues such as pancreas and liver just 20 minutes post-oral inoculation. These results suggest rapid dissemination of diverse viral populations, followed by a major restriction in population diversity and monopolization in all examined tissues.

scholarly journals Rapid Dissemination and Monopolization of Viral Populations in Mice Revealed Using a Panel of Barcoded Viruses

2019 ◽  
Vol 94 (2) ◽  
Author(s):  
Broc T. McCune ◽  
Matthew R. Lanahan ◽  
Benjamin R. tenOever ◽  
Julie K. Pfeiffer
Keyword(s):  
Population Dynamics ◽  
Gastrointestinal Tract ◽  
Enteric Virus ◽  
Population Diversity ◽  
Viral Population ◽  
Viral Genomes ◽  
Systemic Dissemination ◽  
Mouse Tissues ◽  
Oral Inoculation ◽  
Rapid Dissemination

ABSTRACT The gastrointestinal tract presents a formidable barrier for pathogens to initiate infection. Despite this barrier, enteroviruses, including coxsackievirus B3 (CVB3), successfully penetrate the intestine to initiate infection and spread systemically prior to shedding in stool. However, the effect of the gastrointestinal barrier on CVB3 population dynamics is relatively unexplored, and the selective pressures acting on CVB3 in the intestine are not well characterized. To examine viral population dynamics in orally infected mice, we produced over 100 CVB3 clones harboring nine unique nucleotide “barcodes.” Using this collection of barcoded viruses, we found diverse viral populations throughout each mouse within the first day postinfection, but by 48 h the viral populations were dominated by fewer than three barcoded viruses in intestinal and extraintestinal tissues. Using light-sensitive viruses to track replication status, we found that diverse viruses had replicated prior to loss of diversity. Sequencing whole viral genomes from samples later in infection did not reveal detectable viral adaptations. Surprisingly, orally inoculated CVB3 was detectable in pancreas and liver as soon as 20 min postinoculation, indicating rapid systemic dissemination. These results suggest rapid dissemination of diverse viral populations, followed by a major restriction in population diversity and monopolization in all examined tissues. These results underscore a complex dynamic between dissemination and clearance for an enteric virus. IMPORTANCE Enteric viruses initiate infection in the gastrointestinal tract but can disseminate to systemic sites. However, the dynamics of viral dissemination are unclear. In this study, we created a library of 135 barcoded coxsackieviruses to examine viral population diversity across time and space following oral inoculation of mice. Overall, we found that the broad population of viruses disseminates early, followed by monopolization of mouse tissues with three or fewer pool members at later time points. Interestingly, we detected virus in systemic tissues such as pancreas and liver just 20 min after oral inoculation. These results suggest rapid dissemination of diverse viral populations, followed by a major restriction in population diversity and monopolization in all examined tissues.

scholarly journals Emergence of novel SARS-CoV-2 variants in the Netherlands

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aysun Urhan ◽  
Thomas Abeel
Keyword(s):  
The Netherlands ◽  
Population Diversity ◽  
Genomic Variation ◽  
Population Variation ◽  
Reference Sequence ◽  
Viral Population ◽  
Phylogenetic Study ◽  
First Case ◽  
Novel Variants ◽  
Frequent Mutations

AbstractCoronavirus disease 2019 (COVID-19) has emerged in December 2019 when the first case was reported in Wuhan, China and turned into a pandemic with 27 million (September 9th) cases. Currently, there are over 95,000 complete genome sequences of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, in public databases, accompanying a growing number of studies. Nevertheless, there is still much to learn about the viral population variation when the virus is evolving as it continues to spread. We have analyzed SARS-CoV-2 genomes to identify the most variant sites, as well as the stable, conserved ones in samples collected in the Netherlands until June 2020. We identified the most frequent mutations in different geographies. We also performed a phylogenetic study focused on the Netherlands to detect novel variants emerging in the late stages of the pandemic and forming local clusters. We investigated the S and N proteins on SARS-CoV-2 genomes in the Netherlands and found the most variant and stable sites to guide development of diagnostics assays and vaccines. We observed that while the SARS-CoV-2 genome has accumulated mutations, diverging from reference sequence, the variation landscape is dominated by four mutations globally, suggesting the current reference does not represent the virus samples circulating currently. In addition, we detected novel variants of SARS-CoV-2 almost unique to the Netherlands that form localized clusters and region-specific sub-populations indicating community spread. We explored SARS-CoV-2 variants in the Netherlands until June 2020 within a global context; our results provide insight into the viral population diversity for localized efforts in tracking the transmission of COVID-19, as well as sequenced-based approaches in diagnostics and therapeutics. We emphasize that little diversity is observed globally in recent samples despite the increased number of mutations relative to the established reference sequence. We suggest sequence-based analyses should opt for a consensus representation to adequately cover the genomic variation observed to speed up diagnostics and vaccine design.

scholarly journals The absence of murine cathelicidin-related antimicrobial peptide impacts host responses enhancing Salmonella enterica serovar Typhimurium infection

Gut Pathogens ◽  
2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Danisa M. Bescucci ◽  
Sandra T. Clarke ◽  
Catherine L. J. Brown ◽  
Valerie F. Boras ◽  
Tony Montina ◽  
...  
Keyword(s):  
Antimicrobial Peptide ◽  
Salmonella Enterica ◽  
Systemic Infection ◽  
Cell Loss ◽  
Host Responses ◽  
Post Inoculation ◽  
Systemic Dissemination ◽  
Serovar Typhimurium ◽  
The Impact

Abstract Background Cathelicidins are a class of antimicrobial peptide, and the murine cathelicidin-related antimicrobial peptide (mCRAMP) has been demonstrated in vitro to impair Salmonella enterica serovar Typhimurium proliferation. However, the impact of mCRAMP on host responses and the microbiota following S. Typhimurium infection has not been determined. In this study mCRAMP−/− and mCRAMP+/+ mice (± streptomycin) were orally inoculated with S. enterica serovar Typhimurium DT104 (SA +), and impacts on the host and enteric bacterial communities were temporally evaluated. Results Higher densities of the pathogen were observed in cecal digesta and associated with mucosa in SA+/mCRAMP−/− mice that were pretreated (ST+) and not pretreated (ST−) with streptomycin at 24 h post-inoculation (hpi). Both SA+/ST+/mCRAMP−/− and SA+/ST−/mCRAMP−/− mice were more susceptible to infection exhibiting greater histopathologic changes (e.g. epithelial injury, leukocyte infiltration, goblet cell loss) at 48 hpi. Correspondingly, immune responses in SA+/ST+/mCRAMP–/− and SA+/ST−/mCRAMP–/− mice were affected (e.g. Ifnγ, Kc, Inos, Il1β, RegIIIγ). Systemic dissemination of the pathogen was characterized by metabolomics, and the liver metabolome was affected to a greater degree in SA+/ST+/mCRAMP–/− and SA+/ST−/mCRAMP–/− mice (e.g. taurine, cadaverine). Treatment-specific changes to the structure of the enteric microbiota were associated with infection and mCRAMP deficiency, with a higher abundance of Enterobacteriaceae and Veillonellaceae observed in infected null mice. The microbiota of mice that were administered the antibiotic and infected with Salmonella was dominated by Proteobacteria. Conclusion The study findings showed that the absence of mCRAMP modulated both host responses and the enteric microbiota enhancing local and systemic infection by Salmonella Typhimurium.

scholarly journals Introduction, Evolution, and Dissemination of Influenza A Viruses in Exhibition Swine in the United States during 2009 to 2013

2016 ◽  
Vol 90 (23) ◽  
pp. 10963-10971 ◽  
Author(s):  
Martha I. Nelson ◽  
Karla M. Stucker ◽  
Seth A. Schobel ◽  
Nídia S. Trovão ◽  
Suman R. Das ◽  
...  
Keyword(s):  
United States ◽  
Population Dynamics ◽  
Influenza A Virus ◽  
Influenza A ◽  
The United States ◽  
Viral Population ◽  
Influenza A Viruses ◽  
Swine Industry ◽  
Virus Diversity ◽  
Agricultural Fairs

ABSTRACT The swine-human interface created at agricultural fairs, along with the generation of and maintenance of influenza A virus diversity in exhibition swine, presents an ongoing threat to public health. Nucleotide sequences of influenza A virus isolates collected from exhibition swine in Ohio ( n = 262) and Indiana ( n = 103) during 2009 to 2013 were used to investigate viral evolution and movement within this niche sector of the swine industry. Phylogenetic and Bayesian analyses were employed to identify introductions of influenza A virus to exhibition swine and study viral population dynamics. In 2013 alone, we identified 10 independent introductions of influenza A virus into Ohio and/or Indiana exhibition swine. Frequently, viruses from the same introduction were identified at multiple fairs within the region, providing evidence of rapid and widespread viral movement within the exhibition swine populations of the two states. While pigs moving from fair to fair to fair is possible in some locations, the concurrent detection of nearly identical strains at several fairs indicates that a common viral source was more likely. Importantly, we detected an association between the high number of human variant H3N2 (H3N2v) virus infections in 2012 and the widespread circulation of influenza A viruses of the same genotype in exhibition swine in Ohio fairs sampled that year. The extent of viral diversity observed in exhibition swine and the rapidity with which it disseminated across long distances indicate that novel strains of influenza A virus will continue to emerge and spread within exhibition swine populations, presenting an ongoing threat to humans. IMPORTANCE Understanding the underlying population dynamics of influenza A viruses in commercial and exhibition swine is central to assessing the risk for human infections with variant viruses, including H3N2v. We used viral genomic sequences from isolates collected from exhibition swine during 2009 to 2013 to understand how the peak of H3N2v cases in 2012 relates to long-term trends in the population dynamics of pandemic viruses recently introduced into commercial and exhibition swine in the United States. The results of our spatial analysis underscore the key role of rapid viral dispersal in spreading multiple genetic lineages throughout a multistate network of agricultural fairs, providing opportunities for divergent lineages to coinfect, reassort, and generate new viral genotypes. The higher genetic diversity of genotypes cocirculating in exhibition swine since 2013 could facilitate the evolution of new reassortants, potentially with even greater ability to cause severe infections in humans or cause human-to-human transmission, highlighting the need for continued vigilance.

scholarly journals Metagenomic Analysis of the Viromes of Three North American Bat Species: Viral Diversity among Different Bat Species That Share a Common Habitat

2010 ◽  
Vol 84 (24) ◽  
pp. 13004-13018 ◽  
Author(s):  
Eric F. Donaldson ◽  
Aimee N. Haskew ◽  
J. Edward Gates ◽  
Jeremy Huynh ◽  
Clea J. Moore ◽  
...  
Keyword(s):  
North American ◽  
Population Diversity ◽  
Myotis Lucifugus ◽  
Viral Population ◽  
Tissue Samples ◽  
Big Brown Bats ◽  
Large Numbers ◽  
Natural Hosts ◽  
Reservoir Hosts

ABSTRACT Effective prediction of future viral zoonoses requires an in-depth understanding of the heterologous viral population in key animal species that will likely serve as reservoir hosts or intermediates during the next viral epidemic. The importance of bats as natural hosts for several important viral zoonoses, including Ebola, Marburg, Nipah, Hendra, and rabies viruses and severe acute respiratory syndrome-coronavirus (SARS-CoV), has been established; however, the large viral population diversity (virome) of bats has been partially determined for only a few of the ∼1,200 bat species. To assess the virome of North American bats, we collected fecal, oral, urine, and tissue samples from individual bats captured at an abandoned railroad tunnel in Maryland that is cohabitated by 7 to 10 different bat species. Here, we present preliminary characterization of the virome of three common North American bat species, including big brown bats (Eptesicus fuscus), tricolored bats (Perimyotis subflavus), and little brown myotis (Myotis lucifugus). In samples derived from these bats, we identified viral sequences that were similar to at least three novel group 1 CoVs, large numbers of insect and plant virus sequences, and nearly full-length genomic sequences of two novel bacteriophages. These observations suggest that bats encounter and disseminate a large assortment of viruses capable of infecting many different animals, insects, and plants in nature.

scholarly journals Sex-Dependent Intestinal Replication of an Enteric Virus

2017 ◽  
Vol 91 (7) ◽  
Author(s):  
Christopher M. Robinson ◽  
Yao Wang ◽  
Julie K. Pfeiffer
Keyword(s):  
Gastrointestinal Tract ◽  
Viral Replication ◽  
Sex Hormones ◽  
Viral Infections ◽  
Type I Interferon ◽  
Enteric Virus ◽  
Interferon Response ◽  
Sex Bias ◽  
Type I ◽  
Peripheral Tissues

ABSTRACT Coxsackievirus is an enteric virus that initiates infection in the gastrointestinal tract before disseminating to peripheral tissues to cause disease, but intestinal factors that influence viral replication are understudied. Furthermore, a sex bias for severe sequelae from coxsackievirus infections has been observed in humans. While mouse models mimicking human pathogenesis have been well characterized, many of these experiments use intraperitoneal injection of coxsackievirus to infect mice, bypassing the intestine. In light of recent studies identifying intestinal factors, such as the microbiota, that alter enteric viral replication, we sought to investigate coxsackievirus replication within the intestine. Here, we orally infected mice with coxsackievirus B3 (CVB3) and found that CVB3 replication in the intestine is sex dependent. CVB3 replicated efficiently in the intestine of male mice but not female mice. Additionally, we found that the type I interferon response and sex hormones can alter both viral replication and lethality. Overall, these data suggest that sex and the immune response play a vital role in CVB3 replication in the intestine and should be considered in light of the sex bias observed in human disease. IMPORTANCE Sex bias in severe sequelae from enteric viral infections has been observed. Since viruses have evolved to achieve optimal levels of fitness in their environmental niches, it is imperative to study viruses at the site of initial replication. Here, we used an oral inoculation system for CVB3, which follows the natural route of infection in the gastrointestinal tract. We found that sex can influence the replication of CVB3 in the intestine. Additionally, the type I interferon response and sex hormones alter both CVB3 intestinal replication and lethality. Overall this work highlights the fact that sex should be considered in investigations of enteric viral replication and pathogenesis.

scholarly journals An Attenuated Escherichia coli K88ac LT(S63K)ΔSTb Efficiently Provides Protection Against Enterotoxigenic Escherichia coli in the Mouse Model

2021 ◽  
Vol 7 ◽  
Author(s):  
Xinyu Zhang ◽  
Shupei Yu ◽  
Darong Cheng ◽  
Yu Feng ◽  
Yuefei Yang ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Wild Strain ◽  
Enterotoxigenic Escherichia Coli ◽  
Post Inoculation ◽  
Ileal Loop ◽  
E Coli ◽  
Oral Inoculation ◽  
Attenuated Isolate ◽  
Efficient Protection ◽  
Site Mutagenesis

To develop an attenuated vaccine candidate against K88ac enterotoxigenic Escherichia coli (ETEC), a novel Escherichia coli (E. coli) K88ac LT(S63K)ΔSTb with LT(S63K) mutation and ST1 deletion was generated using site mutagenesis and λ-Red homologous recombination based on wild paternal ETEC strain C83902. E. coli K88ac LT(S63K)ΔSTb showed very similar fimbriae expression and growth kinetics to the wild strain C83902, but it was significantly attenuated according to the results of a rabbit ligated ileal loop assay and mouse infection study. Oral inoculation with E. coli K88ac LT(S63K)ΔSTb stimulated the mucosa immune response and induced the secretion of IgA to K88ac in the intestines in mice. A challenge experiment revealed that the attenuated strain provided efficient protection against C83902 in the following 7 days and at the 24th day post-inoculation, suggesting that the attenuated isolate could act as an ecological protectant and vaccine in preventing K88ac ETEC.

scholarly journals The evolution of a super-swarm of foot-and-mouth disease virus in cattle

2019 ◽  
Author(s):  
Jonathan Arzt ◽  
Ian Fish ◽  
Steven J. Pauszek ◽  
Shannon L. Johnson ◽  
Patrick S. Chain ◽  
...  
Keyword(s):  
Foot And Mouth Disease ◽  
Population Diversity ◽  
Mouth Disease ◽  
Viral Population ◽  
Coding Region ◽  
Experimental Conditions ◽  
Genomic Changes ◽  
Natural Host Species ◽  
Mouth Disease Virus ◽  
Foot And Mouth

AbstractFoot-and-mouth disease (FMD) is a highly contagious viral disease that severely impacts global food security and is one of the greatest constraints on international trade of animal products. Extensive viral population diversity and rapid, continuous mutation of circulating FMD viruses (FMDVs) pose significant obstacles to the control and ultimate eradication of this important transboundary pathogen. The current study investigated mechanisms contributing to within-host evolution of FMDV in a natural host species (cattle). Specifically, vaccinated and non-vaccinated cattle were infected with FMDV under controlled, experimental conditions and subsequently sampled for up to 35 days to monitor viral genomic changes as related to phases of disease and experimental cohorts. Consensus-level genomic changes across the entire FMDV coding region were characterized through three previously defined stages of infection: early, transitional, and persistent. The overall conclusion was that viral evolution occurred via a combination of two mechanisms: emergence of full-genomic minority haplotypes from within the inoculum super-swarm, and concurrent continuous point mutations. Phylogenetic analysis indicated that individuals were infected with multiple distinct haplogroups that were pre-existent within the ancestral inoculum used to infect all animals. Multiple shifts of dominant viral haplotype took place during the early and transitional phases of infection, whereas few shifts occurred during persistent infection. These insights into FMDV population dynamics have important implications for virus sampling methodology and molecular epidemiology.

scholarly journals Molecular Evolution of Human Norovirus GII.2 Clusters

2021 ◽  
Vol 12 ◽  
Author(s):  
Xingguang Li ◽  
Haizhou Liu ◽  
Brittany Rife Magalis ◽  
Sergei L. Kosakovsky Pond ◽  
Erik M. Volz
Keyword(s):  
Population Dynamics ◽  
Selection Pressure ◽  
Evolutionary Rate ◽  
Winter Season ◽  
Viral Population ◽  
Evolutionary Adaptation ◽  
Effective Population ◽  
Human Norovirus ◽  
The Past ◽  
Norovirus Gii

BackgroundThe human norovirus GII.2 outbreak during the 2016–2017 winter season was of unprecedented scale and geographic distribution.MethodsWe analyzed 519 complete VP1 gene sequences of the human norovirus GII.2 genotype sampled during the 2016–2017 winter season, as well as prior (dating back to 1976) from 7 countries. Phylodynamic analyses of these sequences were performed using maximum likelihood and Bayesian statistical frameworks in order to estimate viral evolutionary and population dynamics associated with the outbreak.ResultsOur results revealed an increase in the genetic diversity of human norovirus GII.2 during the recent Asian outbreak and diversification was characterized by at least eight distinct clusters. Bayesian estimation of viral population dynamics revealed a highly fluctuating effective population size, increasing in frequency during the past 15 years.ConclusionDespite an increasing viral diversity, we found no evidence of an elevated evolutionary rate or significant selection pressure in human norovirus GII.2, indicating viral evolutionary adaptation was not responsible for the volatility of or spread of the virus during this time.

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