Viral Population Dynamics Research Articles

Design, optimization, and inference of biphasic decay of infectious virus particles.

Virus population dynamics are driven by counter-balancing forces of production and loss. Whereas viral production arises from complex interactions with susceptible hosts, the loss of infectious virus particles is often approximated as a first-order kinetic process. As such, experimental protocols to measure infectious virus loss are not typically designed to identify non-exponential decay processes. Here, we propose methods to evaluate if an experimental design is adequate to identify multiphasic virus particle decay and to optimize the sampling times of decay experiments, accounting for uncertainties in viral kinetics. First, we evaluate synthetic scenarios of biphasic decays, with varying decay rates and initial proportions of subpopulations. We show that robust inference of multiphasic decay is more likely when the faster decaying subpopulation predominates insofar as early samples are taken to resolve the faster decay rate. Moreover, design optimization involving non-equal spacing between observations increases the precision of estimation while reducing the number of samples. We then apply these methods to infer multiple decay rates associated with the decay of bacteriophage ('phage') , an evolved isolate derived from phage . A pilot experiment confirmed that decay is multiphasic, but was unable to resolve the rate or proportion of the fast decaying subpopulation(s). We then applied a Fisher information matrix-based design optimization method to propose non-equally spaced sampling times. Using this strategy, we were able to robustly estimate multiple decay rates and the size of the respective subpopulations. Notably, we conclude that the vast majority (94%) of the phage population decays at a rate 16-fold higher than the slow decaying population. Altogether, these results provide both a rationale and a practical approach to quantitatively estimate heterogeneity in viral decay.

Sacbrood viruses and select Lake Sinai virus variants dominated Apis mellifera colonies symptomatic for European foulbrood.

European foulbrood (EFB) is a prevalent disease in the European honey bee (Apis mellifera) in the United States, which can lead to colony decline and collapse. The bacterial components of EFB are well-studied, but the diversity of viral infections within infected colonies has not been explored. In this study, we use meta-transcriptomics sequencing of 12 honey bee hives, symptomatic (+, n = 6) and asymptomatic (-, n = 6) for EFB, to investigate viral infection associated with the disease. We assembled 41 viral genomes, belonging to three families (Iflaviridae, Dicistroviridae, and Sinhaliviridae), all previously reported in honey bees, including Lake Sinai virus, deformed wing virus, sacbrood virus, Black queen cell virus, and Israeli acute paralysis virus. In colonies with severe EFB, we observed a higher occurrence of viral genomes (34 genomes) in contrast to fewer recovered from healthy colonies (seven genomes) and a complete absence of Dicistroviridae genomes.We observed specific Lake Sinai virus clades associated exclusively with EFB + or EFB - colonies, in addition to EFB-afflicted colonies that exhibited an increase in relative abundance of sacbrood viruses. Multivariate analyses highlighted that a combination of site and EFB disease status influenced RNA virome composition, while EFB status alone did not significantly impact it, presenting a challenge for comparisons between colonies kept in different yards. These findings contribute to the understanding of viral dynamics in honey bee colonies compromised by EFB and underscore the need for future investigations to consider viral composition when investigating EFB.IMPORTANCEThis study on the viromes of honey bee colonies affected by European foulbrood (EFB) sheds light on the dynamics of viral populations in bee colonies in the context of a prevalent bacterial brood disease. The identification of distinct Lake Sinai virus and sacbrood virus clades associated with colonies affected by severe EFB suggests a potential connection between viral composition and disease status, emphasizing the need for further investigation into the role of viruses during EFB infection. The observed increase in sacbrood viruses during EFB infection suggests a potential viral dysbiosis, with potential implications for honey bee brood health. These findings contribute valuable insights related to beekeeping practices, offering a foundation for future research aimed at understanding and mitigating the impact of bacterial and viral infection in commercial honey bee operations and the management of EFB.

VAMPirus: A versatile amplicon processing and analysis program for studying viruses.

Amplicon sequencing is an effective and increasingly applied method for studying viral communities in the environment. Here, we present vAMPirus, a user-friendly, comprehensive, and versatile DNA and RNA virus amplicon sequence analysis program, designed to support investigators in exploring virus amplicon sequencing data and running informed, reproducible analyses. vAMPirus intakes raw virus amplicon libraries and, by default, performs nucleotide- and amino acid-based analyses to produce results such as sequence abundance information, taxonomic classifications, phylogenies and community diversity metrics. The vAMPirus analytical framework leverages 16 different opensource tools and provides optional approaches that can increase the ratio of biological signal-to-noise and thereby reveal patterns that would have otherwise been masked. Here, we validate the vAMPirus analytical framework and illustrate its implementation as a general virus amplicon sequencing workflow by recapitulating findings from two previously published double-stranded DNA virus datasets. As a case study, we also apply the program to explore the diversity and distribution of a coral reef-associated RNA virus. vAMPirus is streamlined within Nextflow, offering straightforward scalability, standardization and communication of virus lineage-specific analyses. The vAMPirus framework is designed to be adaptable; community-driven analytical standards will continue to be incorporated as the field advances. vAMPirus supports researchers in revealing patterns of virus diversity and population dynamics in nature, while promoting study reproducibility and comparability.

Interferons and tuft cell numbers are bottlenecks for persistent murine norovirus infection.

Noroviruses (NoVs) are a leading cause of viral gastroenteritis. Despite global clinical relevance, our understanding of how host factors, such as antiviral cytokines interferons (IFNs), modulate NoV population dynamics is limited. Murine NoV (MNoV) is a tractable in vivo model for the study of host regulation of NoV. A persistent strain of MNoV, CR6, establishes a reservoir in intestinal tuft cells for chronic viral shedding in stool. However, the influence of host innate immunity and permissive cell numbers on viral population dynamics is an open question. We generated a pool of 20 different barcoded viruses (CR6BC) by inserting 6-nucleotide barcodes at the 3' position of the NS4 gene and used this pool as our viral inoculum for in vivo infections of different mouse lines. We found that over the course of persistent CR6 infection, shed virus was predominantly colon-derived, and viral barcode richness decreased over time irrespective of host immune status, suggesting that persistent infection involves a series of reinfection events. In mice lacking the IFN-λ receptor, intestinal barcode richness was enhanced, correlating with increased viral intestinal replication. IL-4 treatment, which increases tuft cell numbers, also increased barcode richness, indicating the abundance of permissive tuft cells to be a bottleneck during CR6 infection. In mice lacking type I IFN signaling (Ifnar1-/-) or all IFN signaling (Stat1-/-), barcode diversity at extraintestinal sites was dramatically increased, implicating different IFNs as critical bottlenecks at specific tissue sites. Of interest, extraintestinal barcodes were overlapping but distinct from intestinal barcodes, indicating that disseminated virus represents a distinct viral population than that replicating in the intestine. Barcoded viruses are a valuable tool to explore the influence of host factors on viral diversity in the context of establishment and maintenance of infection as well as dissemination and have provided important insights into how NoV infection proceeds in immunocompetent and immunocompromised hosts.

Investigating the dose-dependency of the midgut escape barrier using a mechanistic model of within-mosquito dengue virus population dynamics.

Arboviruses can emerge rapidly and cause explosive epidemics of severe disease. Some of the most epidemiologically important arboviruses, including dengue virus (DENV), Zika virus (ZIKV), Chikungunya (CHIKV) and yellow fever virus (YFV), are transmitted by Aedes mosquitoes, most notably Aedes aegypti and Aedes albopictus. After a mosquito blood feeds on an infected host, virus enters the midgut and infects the midgut epithelium. The virus must then overcome a series of barriers before reaching the mosquito saliva and being transmitted to a new host. The virus must escape from the midgut (known as the midgut escape barrier; MEB), which is thought to be mediated by transient changes in the permeability of the midgut-surrounding basal lamina layer (BL) following blood feeding. Here, we present a mathematical model of the within-mosquito population dynamics of DENV (as a model system for mosquito-borne viruses more generally) that includes the interaction of the midgut and BL which can account for the MEB. Our results indicate a dose-dependency of midgut establishment of infection as well as rate of escape from the midgut: collectively, these suggest that the extrinsic incubation period (EIP)-the time taken for DENV virus to be transmissible after infection-is shortened when mosquitoes imbibe more virus. Additionally, our experimental data indicate that multiple blood feeding events, which more closely mimic mosquito-feeding behavior in the wild, can hasten the course of infections, and our model predicts that this effect is sensitive to the amount of virus imbibed. Our model indicates that mutations to the virus which impact its replication rate in the midgut could lead to even shorter EIPs when double-feeding occurs. Mechanistic models of within-vector viral infection dynamics provide a quantitative understanding of infection dynamics and could be used to evaluate novel interventions that target the mosquito stages of the infection.

Modeling viral evolution: A novel SIRSVIDE framework with application to SARS-CoV-2 dynamics

Understanding evolutionary trends in emerging viruses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is crucial for effective public health management and response. Nonetheless, extensive debates have arisen concerning viral evolutionary trends, particularly the interplay between transmissibility, pathogenicity, and immune escape. In this context, we have developed a novel computational model named SIRSVIDE (Susceptible-Infected-Recovered-Susceptible-Variation-Immune Decay-Immune Escape) to simulate the transmission and evolutionary dynamics of viral populations. Our simulation results indicate that under conditions of high mutation rates, elevated transmission rates, and larger susceptible host populations, viral populations exhibit prolonged increases in transmissibility and immune escape, accompanied by reductions in pathogenicity and noticeable short-term fluctuations. However, when the total susceptible population size and mutation rate decrease, substantial uncertainty in the evolutionary trends of viral populations becomes apparent. In summary, the SIRSVIDE model establishes a comprehensive framework for generating both short- and long-term viral epidemiological and evolutionary dynamics. The simulation outcomes align with existing evidence indicating that SARS-CoV-2 is undergoing selection for heightened transmissibility, decreased pathogenicity, and enhanced immune escape. Furthermore, the model sheds light on the possible evolutionary dynamics of other viruses.

Lymphoid tissues contribute to plasma viral clonotypes early after antiretroviral therapy interruption in SIV-infected rhesus macaques.

The rebound-competent viral reservoir, composed of a virus that is able to persist during antiretroviral therapy (ART) and mediate reactivation of systemic viral replication and rebound viremia after ART interruption (ATI), remains the biggest obstacle to treating HIV infection. A better understanding of the cellular and tissue origins and the dynamics of viral populations that initiate rebound upon ATI could help develop therapeutic strategies for reducing the rebound-competent viral reservoir. In this study, barcoded simian immunodeficiency virus (SIV), SIVmac239M, was used to infect rhesus macaques to enable monitoring of viral barcode clonotypes contributing to virus detectable in plasma after ATI. Blood and tissues from secondary lymphoid organs (spleen, mesenteric lymph nodes, and inguinal lymph nodes) and from the colon, ileum, lung, liver, and brain were analyzed using viral barcode sequencing, intact proviral DNA assay, single-cell RNA sequencing, and combined CODEX and RNAscope in situ hybridization. Four of seven animals had viral barcodes detectable by deep sequencing of plasma at necropsy, although plasma viral RNA remained below 22 copies per milliliter. Among the tissues studied, mesenteric lymph nodes, inguinal lymph nodes, and spleen contained viral barcodes detected in plasma. CD4+ T cells were the main cell type harboring viral RNA after ATI. Furthermore, T cell zones in lymphoid tissues showed higher viral RNA abundance than B cell zones for most animals. These findings are consistent with lymphoid tissues contributing to the virus present in plasma early after ATI.

Investigating the impact of memory effects on computer virus population dynamics: A fractal–fractional approach with numerical analysis

In this study, we investigate the impact of memory effects through the application of the fractal–fractional derivative operator on population dynamics in computer viruses. By utilizing numerical analysis techniques, we explore the influence of varying fractal–fractional operator orders on virus propagation and conduct a parameter study to examine the effects of fractal dimension and fractional order on computer virus spread. Furthermore, in order to comprehensively compare and analyze the outcomes from various perspectives, we introduce a novel application of the operational matrix technique to the proposed dynamical system, transforming the fractal–fractional model into the Caputo derivative form. Two different numerical techniques, Adams–Bashforth and Taylor operational matrix, have been employed to solve the two distinct forms of the model. The obtained results yielded highly consistent outcomes for the two numerical methods employed, despite their utilization of distinct derivative operators. The reported results highlight the memory effect associated with fractal–fractional derivatives, where past states and behaviors continue to influence the system. The ability to capture these memory effects through fractal–fractional derivatives can be considered a benefit, enabling a more comprehensive understanding, analysis and modeling of computer virus dynamics. Additionally, we investigate four variants to ensure numerical stability, employing both the Ulam–Hyers (UH) and Ulam–Hyers–Rassias (UHR) criteria.

Identifying the regional drivers of influenza-like illness in Nova Scotia, Canada, with dominance analysis

The spread of viral pathogens is inherently a spatial process. While the temporal aspects of viral spread at the epidemiological level have been increasingly well characterized, the spatial aspects of viral spread are still understudied due to a striking absence of theoretical expectations of how spatial dynamics may impact the temporal dynamics of viral populations. Characterizing the spatial transmission and understanding the factors driving it are important for anticipating local timing of disease incidence and for guiding more informed control strategies. Using a unique data set from Nova Scotia, Canada, the objective of this study is to apply a new novel method that recovers a spatial network of the influenza-like viral spread where the regions in their dominance are identified and ranked. We, then, focus on identifying regional predictors of those dominant regions. Our analysis uncovers 18 key regional drivers among 112 regions, each distinguished by unique community-level vulnerability factors such as demographic and economic characteristics. These findings offer valuable insights for implementing targeted public health interventions and allocating resources effectively.

Doomed drones? Using passage experiments and mathematical modelling to determine Deformed wing virus population dynamics in male honeybees.

Varroa destructor is an ectoparasitic mite of honeybees which vectors a range of pathogenic viruses, the most notable being Deformed wing virus (DWV). Mites parasitise bees during pupal development and male honeybees, drones, have a longer development cycle than female workers (24 versus 21 days), allow for more progeny mites to develop per foundress (1.6-2.5 compared to 0.7-1.45). How this longer exposure time influences evolution of the transmitted virus population is unknown. Using uniquely tagged viruses recovered from cDNA we investigated the replication, competition and morbidity of DWV genotypes in drones. Assays examining virus replication and morbidity revealed drones are highly susceptible to both predominant genotypes of DWV. In virus passage studies using an equimolar inocula of major DNA genotypes and their recombinants, the recombinant form dominated but did not reach 100% of the virus population within 10 passages. Using an in-silico model of the virus-mite-bee system we examined bottlenecks during virus acquisition by the mite and subsequent injection of viruses into the host, which may play a significant role in shaping virus diversity. This study furthers our understanding of the variables influencing DWV diversity changes and provides insight into areas of future research in the mite-virus-bee system.

Intracellular Diversity of WNV within Circulating Avian Peripheral Blood Mononuclear Cells Reveals Host-Dependent Patterns of Polyinfection.

Arthropod-borne virus (arbovirus) populations exist as mutant swarms that are maintained between arthropods and vertebrates. West Nile virus (WNV) population dynamics are host-dependent. In American crows, 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 leads to fitness gains, whereas that passed in crows does not. Therefore, we tested the hypothesis that high crow viremia allows for 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 molecularly barcoded WNV and sequenced viral RNA from single cells to quantify the number of WNV barcodes in each. 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 the 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.

Long-term monitoring of aphid-transmitted viruses in melon and zucchini crops: genetic diversity and population structure of cucurbit aphid-borne yellows virus and watermelon mosaic virus.

Understanding the emergence and prevalence of viral diseases in crops requires the systematic epidemiological monitoring of viruses, as well as the analysis of how ecological and evolutionary processes combine to shape viral population dynamics. Here, we extensively monitored the occurrence of six aphid-transmitted viruses in melon and zucchini crops in Spain for 10 consecutive cropping seasons between 2011 and 2020. The most prevalent viruses were cucurbit aphid-borne yellows virus (CABYV) and watermelon mosaic virus (WMV), found in 31 and 26% of samples with yellowing and mosaic symptoms. Other viruses, such as zucchini yellow mosaic virus (ZYMV), cucumber mosaic virus (CMV), Moroccan watermelon mosaic virus (MWMV), and papaya ring spot virus (PRSV) were detected less frequently (< 3%) and mostly in mixed infections. Notably, our statistical analysis showed a significant association between CABYV and WMV in melon and zucchini hosts, suggesting that mixed infections might be influencing the evolutionary epidemiology of these viral diseases. We then carried out a comprehensive genetic characterization of the full-length genome sequences of CABYV and WMV isolates by using the PacBio single-molecule real-time high-throughput technology, in order to assess the genetic variation and structure of their populations. Our results showed that most isolates clustered in the Mediterranean clade, with a fine-scale temporal structure, which was in part explained by the level of the variance between isolates from single and mixed infections. In contrast, the WMV population genetic analysis showed that most of the isolates grouped into the Emergent clade, with no genetic differentiation.

Wastewater surveillance uncovers regional diversity and dynamics of SARS-CoV-2 variants across nine states in the USA

Wastewater-based epidemiology (WBE) is a non-invasive and cost-effective approach for monitoring the spread of a pathogen within a community. WBE has been adopted as one of the methods to monitor the spread and population dynamics of the SARS-CoV-2 virus, but significant challenges remain in the bioinformatic analysis of WBE-derived data. Here, we have developed a new distance metric, CoVdist, and an associated analysis tool that facilitates the application of ordination analysis to WBE data and the identification of viral population changes based on nucleotide variants. We applied these new approaches to a large-scale dataset from 18 cities in nine states of the USA using wastewater collected from July 2021 to June 2022. We found that the trends in the shift between the Delta and Omicron SARS-CoV-2 lineages were largely consistent with what was seen in clinical data, but that wastewater analysis offered the added benefit of revealing significant differences in viral population dynamics at the state, city, and even neighborhood scales. We also were able to observe the early spread of variants of concern and the presence of recombinant lineages during the transitions between variants, both of which are challenging to analyze based on clinically-derived viral genomes. The methods outlined here will be beneficial for future applications of WBE to monitor SARS-CoV-2, particularly as clinical monitoring becomes less prevalent. Additionally, these approaches are generalizable, allowing them to be applied for the monitoring and analysis of future viral outbreaks.

Evolution of highly pathogenic H5N1 influenza A virus in the central nervous system of ferrets.

Central nervous system (CNS) disease is the most common extra-respiratory tract complication of influenza A virus infections in humans. Remarkably, zoonotic highly pathogenic avian influenza (HPAI) H5N1 virus infections are more often associated with CNS disease than infections with seasonal influenza viruses. Evolution of avian influenza viruses has been extensively studied in the context of respiratory infections, but evolutionary processes in CNS infections remain poorly understood. We have previously observed that the ability of HPAI A/Indonesia/5/2005 (H5N1) virus to replicate in and spread throughout the CNS varies widely between individual ferrets. Based on these observations, we sought to understand the impact of entrance into and replication within the CNS on the evolutionary dynamics of virus populations. First, we identified and characterized three substitutions-PB1 E177G and A652T and NP I119M - detected in the CNS of a ferret infected with influenza A/Indonesia/5/2005 (H5N1) virus that developed a severe meningo-encephalitis. We found that some of these substitutions, individually or collectively, resulted in increased polymerase activity in vitro. Nevertheless, in vivo, the virus bearing the CNS-associated mutations retained its capacity to infect the CNS but showed reduced dispersion to other anatomical sites. Analyses of viral diversity in the nasal turbinate and olfactory bulb revealed the lack of a genetic bottleneck acting on virus populations accessing the CNS via this route. Furthermore, virus populations bearing the CNS-associated mutations showed signs of positive selection in the brainstem. These features of dispersion to the CNS are consistent with the action of selective processes, underlining the potential for H5N1 viruses to adapt to the CNS.

Population dynamics of Citrus tristeza virus (CTV) in single aphid-transmitted sub-isolates of the South African GFMS12 isolate.

Grapefruit trees in South Africa have been cross protected against severe stem pitting genotypes of Citrus tristeza virus (CTV) since the 1920s using a mild strain initially called 'Nartia' but later referred to as grapefruit mild strain 12 (GFMS12).In the current study, the GFMS12 isolate was used as the source for single aphid transmissions (SAT) using Toxoptera citricida, commonly called the brown citrus aphid (BrCA). The BrCA-transmitted CTV sub-isolates were analyzed by the heteroduplex mobility assay (HMA), serological assays, genetic marker analysis (GMA), and selected sub-isolates were biologically indexed. Reverse transcription PCR of genomic regions was conducted using universal primers followed by cloning the PCR products, HMA and sequence analysis; nine genotypes of CTV were identified in the complex of GFMS12, including both severe and mild genotypes. A singleBrCAtransmitted up to six CTV genotypes simultaneously in one sub-isolate. The HMA was found to be a rapid, reliable tool for the identification of genotypes and can be useful in the development of CTV management strategies and budwood certification programs.

Comparative Fluorescence In Situ Hybridization (FISH) Mapping of Twenty-Three Endogenous Jaagsiekte Sheep Retrovirus (enJSRVs) in Sheep (Ovis aries) and River Buffalo (Bubalus bubalis) Chromosomes.

Simple SummaryThe genome of domestic sheep (Ovis aries) harbors at least twenty-seven copies of enJSRVs, endogenous retroviruses (ERVs) highly related to the exogenous and pathogenic Jaagsiekte sheep betaretrovirus (JSRV). Interestingly, some of these loci are insertionally polymorphic, that is they are present only in some individuals or populations of their host species. This differential distribution of enJSRVs has provided important insights into tracing host and viral evolution. In this study, we report the first comparative fluorescent in situ hybridization (FISH) mapping of genetically characterized enJSRVs in domestic sheep (2n = 54) and river buffalo (Bubalus bubalis, 2n = 50), and reveal a high conservation of enJSRVs chromosome localization between these two species.Endogenous retroviruses (ERVs) are the remnants of ancient infections of host germline cells, thus representing key tools to study host and viral evolution. Homologous ERV sequences often map at the same genomic locus of different species, indicating that retroviral integration occurred in the genomes of the common ancestors of those species. The genome of domestic sheep (Ovis aries) harbors at least twenty-seven copies of ERVs related to the exogenous and pathogenic Jaagsiekte sheep retrovirus (JSRVs), thus referred to as enJSRVs. Some of these loci are unequally distributed between breeds and individuals of the host species due to polymorphic insertions, thereby representing invaluable tools to trace the evolutionary dynamics of virus populations within their hosts. In this study, we extend the cytogenetic physical maps of sheep and river buffalo by performing fluorescent in situ hybridization (FISH) mapping of twenty-three genetically characterized enJSRVs. Additionally, we report the first comparative FISH mapping of enJSRVs in domestic sheep (2n = 54) and river buffalo (Bubalus bubalis, 2n = 50). Finally, we demonstrate that enJSRV loci are conserved in the homologous chromosomes and chromosome bands of both species. Altogether, our results support the hypothesis that enJSRVs were present in the genomes of both species before they differentiated within the Bovidae family.

Human cytomegalovirus strain diversity and dynamics reveal the donor lung as a major contributor after transplantation.

Mixed human cytomegalovirus (HCMV) strain infections are frequent in lung transplant recipients (LTRs). To date, the influence of the donor (D) and recipient (R) HCMV serostatus on intra-host HCMV strain composition and viral population dynamics after transplantation is only poorly understood. Here, we investigated ten pre-transplant lungs from HCMV-seropositive donors and 163 sequential HCMV-DNA-positive plasma and bronchoalveolar lavage samples from fifty LTRs with multiviremic episodes post-transplantation. The study cohort included D+R+ (38 per cent), D+R− (36 per cent), and D−R+ (26 per cent) patients. All samples were subjected to quantitative genotyping by short amplicon deep sequencing, and twenty-four of them were additionally PacBio long-read sequenced for genotype linkages. We find that D+R+ patients show a significantly elevated intra-host strain diversity compared to D+R− and D−R+ patients (P = 0.0089). Both D+ patient groups display significantly higher viral population dynamics than D− patients (P = 0.0061). Five out of ten pre-transplant donor lungs were HCMV DNA positive, whereof three multiple HCMV strains were detected, indicating that multi-strain transmission via lung transplantation is likely. Using long reads, we show that intra-host haplotypes can share distinctly linked genotypes, which limits overall intra-host diversity in mixed infections. Together, our findings demonstrate donor-derived strains as the main source of increased HCMV strain diversity and dynamics post-transplantation. These results foster strategies to mitigate the potential transmission of the donor strain reservoir to the allograft, such as ex vivo delivery of HCMV-selective immunotoxins prior to transplantation to reduce latent HCMV.

Optimal control of mathematical modelling for Ebola virus population dynamics in the presence of vaccination

Ebola virus is a severe often fatal illness in human, which is known to be very dangerous and highly infectious disease that seized many lives in west African countries. In this paper, a mathematical model for the population dynamics of Ebola virus diseases incorporating bats compartment, recovery due to immune response and vaccination was constructed. Pontryagin’s maximum principle has been applied on the model to determine the necessary conditions for the optimal control of the Ebola virus in the presence of vaccination and fruit bats population, the optimality of most of the controls have been analyzed to use a small resources available in other to maximize the performance of the controls. The numerical simulation shows that with small resources if 0.1 percent of the people in a society can be vaccinated daily, Ebola can be mitigated in the environment.

Modeling Virus and Bacteria Populations in Europa's Subsurface Ocean.

The search for life in the universe is often informed by the study of “extreme” environments on Earth, which provide analogs for habitable locations in the Solar System, and whose microbial inhabitants may therefore also serve as analogs for potential life forms in extraterrestrial milieus. Recent work has highlighted the ubiquity and importance of viral entities in terrestrial ecosystems, which calls for a greater understanding of the roles that viruses might play in hypothetical extraterrestrial biomes. While some studies have modeled the dynamics of viral and bacterial populations in icy ocean environments on Earth, previous work has yet to apply these findings to icy ocean worlds such as Jupiter’s moon Europa. It is commonly theorized that hydrothermal vents on Europa could produce the necessary reductants for chemosynthesis to take place on the ocean bottom. In the case that Europa’s ocean is a reductant-limited environment, how might reductants and organic matter reach the sub-ice region to power a more easily accessible ecosystem? Here, we propose a ‘viral elevator,’ a mechanism that functions similarly to the ‘viral shunt’ in Earth’s oceans, which could create and shuttle dissolved organic matter (DOM) to a hypothetical sub-ice biosphere through viral carriers. Current models of Europa’s ocean currents and stratification support the movement of DOM to the sub-ice biosphere. We adapt an existing model for bacterial and viral population dynamics in Earth’s Arctic sea ice to Europa and use parameters from various Arctic-based studies as proxies for Europa’s environment. We find that viral burst size has the most significant effect on the virus-to-bacteria ratio (VBR) and system longevity in closed systems (such as brine pockets within Europa’s icy crust), with higher burst sizes clearly increasing both. When applying our model to an open system with an influx of DOM from the viral elevator, we found that a steady-state system is attainable, with resulting sub-ice biofilms on the order of 0.1 mm thick (global equivalent layer). This has implications for future searches for life on Europa, given that life directly under the ice will be easier to detect and observe than life near the ocean bottom.

Rescuing low frequency variants within intra-host viral populations directly from Oxford Nanopore sequencing data

Infectious disease monitoring on Oxford Nanopore Technologies (ONT) platforms offers rapid turnaround times and low cost. Tracking low frequency intra-host variants provides important insights with respect to elucidating within-host viral population dynamics and transmission. However, given the higher error rate of ONT, accurate identification of intra-host variants with low allele frequencies remains an open challenge with no viable computational solutions available. In response to this need, we present Variabel, a novel approach and first method designed for rescuing low frequency intra-host variants from ONT data alone. We evaluate Variabel on both synthetic data (SARS-CoV-2) and patient derived datasets (Ebola virus, norovirus, SARS-CoV-2); our results show that Variabel can accurately identify low frequency variants below 0.5 allele frequency, outperforming existing state-of-the-art ONT variant callers for this task. Variabel is open-source and available for download at: www.gitlab.com/treangenlab/variabel.