Structurally distinct external solvent-exposed domains drive replication of major human prions
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99 GENERAL AND MISCELLANEOUS↗
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Forecasting Multi-Wave Epidemics Through Bayesian Inference
We present a simple, near-real-time Bayesian method to infer and forecast a multiwave outbreak, and demonstrate it on the COVID-19 pandemic. The approach uses timely epidemiological data that has been widely available for COVID-19. It provides short-term forecasts of the outbreak’s evolution, which can then be used for medical resource planning. The method postulates one- and multiwave infection models, which are convolved with the incubation-period distribution to yield competing disease models. The disease models’ parameters are estimated via Markov chain Monte Carlo sampling and information-theoretic criteria are used to select between them for use in forecasting. The method is demonstrated on two- and three-wave COVID-19 outbreaks in California, New Mexico and Florida, as observed during Summer-Winter 2020. We find that the method is robust to noise, provides useful forecasts (along with uncertainty bounds) and that it reliably detected when the initial single-wave COVID-19 outbreaks transformed into successive surges as containment efforts in these states failed by the end of Spring 2020.
59 BASIC BIOLOGICAL SCIENCES↗
Persistence of viral RNA in North American elk experimentally infected with an ancestral strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
Abstract White-tailed deer (Odocoileus virginianus) have emerged as a reservoir host for SARS-CoV-2 given their susceptibility to infection and demonstrated high rates of seroprevalence and infection across the United States. As SARS-CoV-2 circulates within free-ranging white-tailed deer populations, there is the risk of transmission to other wildlife species and even back to the human population. The goal of this study was to determine the susceptibility, shedding, and immune response of North American elk (Cervus elaphus canadensis) to experimental infection with SARS-CoV-2, to determine if another wide-ranging cervid species could potentially serve as a reservoir host for the virus. Here we demonstrate that while North American elk do not develop clinical signs of disease, they do develop a neutralizing antibody response to infection, suggesting the virus is capable of replicating in this mammalian host. Additionally, we demonstrate SARS-CoV-2 RNA presence in the medial retropharyngeal lymph nodes of infected elk three weeks after experimental infection. Consistent with previous observations in humans, these data may highlight a mechanism of viral persistence for SARS-CoV-2 in elk.
Science & Technology - Other Topics↗
Million Worker Study
Radiation health issues have been an important aspect of DOE's Worker Safety and Health programs. The goal is to ensure that workers are adequately protected from the various radiological hazards associated with DOE sites and operations. Since the early 1940’s DOE has supported the conduct of epidemiologic studies of practically every DOE (AEC) facility and collected these data, now managed by the Oak Ridge Associated Universities (ORAU), in remarkable detail. In the early 2000s, the Office of Health, Safety and Security authorized access to specific DOE worker datasets. Shortly thereafter, the DOE Office of Science provided funds for a pilot study that confirmed the feasibility of the Million Worker Study (MWS), and then additional resources were provided (with other agencies) to extend the follow-up of many populations, not just DOE workers, but also atomic veterans, industrial radiographers, nuclear power plant workers and medical radiation workers (the Million Persons Study (MPS)). This proposal was a continuation of support provided by DOE, specifically to extend the follow-up of the worker populations at the Mallinckrodt Chemical Works (MCW) and Los Alamos National Laboratory (LANL). The work addresses DOE’s interest in clarifying the health risks of their workers as well as contributing knowledge on radiation risks that is relevant today with regard to compensation schemes. The findings are also important for the US public in light of the increased population exposure to medical imaging, environmental circumstances such as hydraulic fracturing, increased exposures during high altitude flights, and with regard to nuclear accidents such as Fukushima and possible terrorist events. Furthermore, it is important to consider reducing the uncertainty in current risk estimates by developing risk coefficients based on healthy American workers who are more representative of U.S. workers and the general public than 1945 Japanese survivors of the atomic bombs living in a war-torn country which experienced deprivation, malnourishment, and increased rates of infections and other diseases. But more importantly, it is important to learn whether radiation exposures received gradually over time (e.g., years) are more or less effective in causing health effects, cancer in particular, than if the radiation dose is received all at once in a fraction of a second as experienced by the Japanese atomic bomb survivors. Finally, the ability to evaluate and combine large populations with intakes of radionuclides such as uranium, radium, plutonium, americium and polonium will provide new quantitative knowledge on human health effects that hitherto has not been possible. This cost-efficient study has built on the investments made and foundations laid by investigators and government agencies, including DOE, over the past 30-40 years, which have established early worker cohorts that can now provide answers to questions on the lifetime human health risks associated with low-level radiation exposures. Collaborating institutions included: International Epidemiology Institute, Oak Ridge Associated Universities, Oak Ridge National Laboratory, Los Alamos National Laboratory, Landauer, Inc., and Vanderbilt University. Follow-up of these two populations and the integration of them with the many other cohorts (now a total of 31) in the MPS continues under a separate DOE grant (DE-AU0000046).
61 RADIATION PROTECTION AND DOSIMETRY↗
Investigating the impact of environmental factors on West Nile virus human case prediction in Ontario, Canada
West Nile virus is the most common mosquito borne disease in North America and the leading cause of viral encephalitis. West Nile virus is primarily transmitted between birds and mosquitoes while humans are incidental, dead-end hosts. Climate change may increase the risk of human infections as climatic variables have been shown to affect the mosquito life cycle, biting rate, incubation period of the disease in mosquitoes, and bird migration patterns. We develop a zero-inflated Poisson model to investigate how human West Nile virus case counts vary with respect to mosquito abundance and infection rates, bird abundance, and other environmental covariates. We use a Bayesian paradigm to fit our model to data from 2010–2019 in Ontario, Canada. Our results show mosquito infection rate, temperature, precipitation, and crow abundance are positively correlated with human cases while NDVI and robin abundance are negatively correlated with human cases. We find the inclusion of spatial random effects allows for more accurate predictions, particularly in years where cases are higher. Our model is able to accurately predict the magnitude and timing of yearly West Nile virus outbreaks and could be a valuable tool for public health officials to implement prevention strategies to mitigate these outbreaks.
60 APPLIED LIFE SCIENCES↗
Dissecting Phenotype from Genotype with Clinical Isolates of SARS-CoV-2 First Wave Variants
The emergence and availability of closely related clinical isolates of SARS-CoV-2 offers a unique opportunity to identify novel nonsynonymous mutations that may impact phenotype. Global sequencing efforts show that SARS-CoV-2 variants have emerged and then been replaced since the beginning of the pandemic, yet we have limited information regarding the breadth of variant-specific host responses. Using primary cell cultures and the K18-hACE2 mouse, we investigated the replication, innate immune response, and pathology of closely related, clinical variants circulating during the first wave of the pandemic. Mathematical modeling of the lung viral replication of four clinical isolates showed a dichotomy between two B.1. isolates with significantly faster and slower infected cell clearance rates, respectively. While isolates induced several common immune host responses to infection, one B.1 isolate was unique in the promotion of eosinophil-associated proteins IL-5 and CCL11. Moreover, its mortality rate was significantly slower. Lung microscopic histopathology suggested further phenotypic divergence among the five isolates showing three distinct sets of phenotypes: (i) consolidation, alveolar hemorrhage, and inflammation, (ii) interstitial inflammation/septal thickening and peribronchiolar/perivascular lymphoid cells, and (iii) consolidation, alveolar involvement, and endothelial hypertrophy/margination. Together these findings show divergence in the phenotypic outcomes of these clinical isolates and reveal the potential importance of nonsynonymous mutations in nsp2 and ORF8.
60 APPLIED LIFE SCIENCES↗
COVID-19 Exposure Assessment Tool (CEAT): Exposure quantification based on ventilation, infection prevalence, group characteristics, and behavior
The coronavirus disease 2019 (COVID-19) Exposure Assessment Tool (CEAT) allows users to compare respiratory relative risk to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for various scenarios, providing understanding of how combinations of protective measures affect risk. CEAT incorporates mechanistic, stochastic, and epidemiological factors including the (i) emission rate of virus, (ii) viral aerosol degradation and removal, (iii) duration of activity/exposure, (iv) inhalation rates, (v) ventilation rates (indoors/outdoors), (vi) volume of indoor space, (vii) filtration, (viii) mask use and effectiveness, (ix) distance between people (taking into account both near-field and far-field effects of proximity), (x) group size, (xi) current infection rates by variant, (xii) prevalence of infection and immunity in the community, (xiii) vaccination rates, and (xiv) implementation of COVID-19 testing procedures. CEAT applied to published studies of COVID-19 transmission events demonstrates the model’s accuracy. We also show how health and safety professionals at NASA Ames Research Center used CEAT to manage potential risks posed by SARS-CoV-2 exposures.
60 APPLIED LIFE SCIENCES↗
Artemether-Lumefantrine Treatment Selects Plasmodium falciparum Multidrug Resistance 1 ( pfmdr1 ) Increased Copy Number Among African Malaria Infections
Abstract Background Decreased efficacy of artemether-lumefantrine, the globally most used antimalarial, has recently emerged in Africa. Methods An efficacy trial was carried out based on directly observed artemether-lumefantrine therapy at Bengo, Northern Angola. One-hundred Plasmodium falciparum uncomplicated malaria patients (2–10 years old) were enrolled, hospitalized for the treatment period, and followed up for 42 days. Polymerase chain reaction (PCR) correction was performed with pfmsp1/2 plus glurp, with analysis considering 2 or 3 coincident markers. Infections were tested by quantitative PCR (qPCR) for pfmdr1 copy number (pfmdr1×N), a potential P. falciparum marker of lumefantrine resistance previously identified in the region. In vitro clone mixtures were built and used to determine the relation between qPCR copy number scores and actual intrainfection quantitative fractions of pfmdr1×N. Results We observed a significant posttreatment selection of gene amplification, suggesting a role in the parasite in vivo response to this drug. pfmdr1×2 qPCR scores of 1.3, 1.4, and 1.5 were determined to correspond to 15%, 25%, and 35% intrainfection rates. Patients carrying infections with a score ≥1.4 at baseline were linked to decreased artemether-lumefantrine day 42 efficacy (79% vs 97% single-copy pfmdr1). All infections were pfmdr1 N86 carriers and no pfk13 mutations were found. Conclusions Our study suggests pfmdr1×N as a marker of P. falciparum in vivo response to lumefantrine in Africa, while indicating patients carrying infections with a pretreatment pfmdr1×N score ≥1.4 before treatment are a group experiencing decreased artemether-lumefantrine performance.
Fançony, Claudia (ORCID:0000000344211769)↗
Expanding Medicaid to Reduce Human Immunodeficiency Virus Transmission in Houston, Texas
Context: Medicaid expansion has been nationally shown to improve engagement in the human immunodeficiency virus (HIV) treatment and prevention continua, which are vital steps to stopping the HIV epidemic. New HIV infections in the United States are disproportionately concentrated among young Black men who have sex with men (YBMSM). Houston, TX, is the most populous city in the Southern United States with a racially/ethnically diverse population that is located in 1 of 11 US states that have not yet expanded Medicaid coverage as of 2021. Methods: An agent-based model that incorporated the sexual networks of YBMSM was used to simulate improved antiretroviral treatment and pre-exposure prophylaxis (PrEP) engagement through Medicaid expansion in Houston, TX. Analyses considered the HIV incidence (number of new infections and as a rate metric) among YBMSM over the next 10 years under Medicaid expansion as the primary outcome. Additional scenarios, involving viral suppression and PrEP uptake above the projected levels achieved under Medicaid expansion, were also simulated. Results: The baseline model projected an HIV incidence rate of 4.96 per 100 person years (py) and about 368 new annual HIV infections in the 10th year. Improved HIV treatment and prevention continua engagement under Medicaid expansion resulted in a 14.9% decline in the number of annual new HIV infections in the 10th year. Increasing viral suppression by an additional 15% and PrEP uptake by 30% resulted in a 44.0% decline in new HIV infections in the 10th year, and a 27.1% decline in cumulative infections across the 10 years of the simulated intervention. Findings: Simulation results indicate that Medicaid expansion has the potential to reduce HIV incidence among YBMSM in Houston. Achieving HIV elimination objectives, however, might require additional effective measures to increase antiretroviral treatment and PrEP uptake beyond the projected improvements under expanded Medicaid.
60 APPLIED LIFE SCIENCES↗
Towards modeling phage therapy
Patients infected with life-threatening multi-drug resistant (MDR) bacteria have been treated with cocktails of bacteriophages. This is a complicated form of personalized medicine as the phages given to a patient have to be selected beforehand on the basis of their lytic capacity of the infecting bacteria. Because bacteria rapidly become resistant, the evolution of resistance to a diverse cocktail of phages is a complicated dynamical process, during which competing bacterial strains replace one another by accumulating several resistance mechanisms, each of which may involve a fitness cost. As a consequence, it is typically not known why a particular phage therapy succeeded or failed, and how one can optimize the composition of the cocktails to maximize the rate of success. To improve upon this, we extend an existing in vivo -calibrated mouse model into a novel mathematical model for the human situation, and include multiple phages infecting multiple bacterial strains, differing in their resistance to each of the phages. We adjust several parameter estimates of the bacterial model to the human situation, and use the model to describe a successful case of phage therapy involving several cocktails, each containing several phages. In the model, treatment success crucially depended on pretreatment resistance levels, and on the diversity and the timing of the cocktails. Once an appropriate cocktail is found, it is less important to further optimize the infection rates of the phages. Resistant bacterial strains expand rapidly when sensitive strains decline, and the higher the infectivity of the phages, the faster resistant strains expand. Because resistance evolves rapidly, it is best to provide a diverse set of phages right from the start of therapy, i.e., to hit hard and early, and create a high genetic barrier to bacterial resistance.
59 BASIC BIOLOGICAL SCIENCES↗
Herpes simplex virus and rates of cognitive decline or whole brain atrophy in the Dominantly Inherited Alzheimer Network
Abstract Objective To investigate whether herpes simplex virus type 1 (HSV‐1) infection was associated with rates of cognitive decline or whole brain atrophy among individuals from the Dominantly Inherited Alzheimer Network (DIAN). Methods Among two subsets of the DIAN cohort (age range 19.6–66.6 years; median follow‐up 3.0 years) we examined (i) rate of cognitive decline ( N = 164) using change in mini‐mental state examination (MMSE) score, (ii) rate of whole brain atrophy ( N = 149), derived from serial MR imaging, calculated using the boundary shift integral (BSI) method. HSV‐1 antibodies were assayed in baseline sera collected from 2009–2015. Linear mixed‐effects models were used to compare outcomes by HSV‐1 seropositivity and high HSV‐1 IgG titres/IgM status. Results There was no association between baseline HSV‐1 seropositivity and rates of cognitive decline or whole brain atrophy. Having high HSV‐1 IgG titres/IgM was associated with a slightly greater decline in MMSE points per year (difference in slope − 0.365, 95% CI: −0.958 to −0.072), but not with rate of whole brain atrophy. Symptomatic mutation carriers declined fastest on both MMSE and BSI measures, however, this was not influenced by HSV‐1. Among asymptomatic mutation carriers, rates of decline on MMSE and BSI were slightly greater among those who were HSV‐1 seronegative. Among mutation‐negative individuals, no differences were seen by HSV‐1. Stratifying by APOE4 status yielded inconsistent results. Interpretation We found no evidence for a major role of HSV‐1, measured by serum antibodies, in cognitive decline or whole brain atrophy among individuals at high risk of early‐onset AD.
Warren‐Gash, Charlotte↗
Investigation of potential aerosol transmission and infectivity of SARS-CoV-2 through central ventilation systems
Here we evaluate the concentrations and probabilities of infection for both building interior and exterior exposure sources using a well-mixed model in a connected multizone building. As a central hub of many community and economic activities, buildings provide social connectivity, but the COVID-19 pandemic has reduced social connectivity due to concerns of viral spread within buildings. Although single zone models of infectious spread are well studied, the impact of aerosolized spread of SARS-CoV-2 via air handling systems in multizone buildings remains unexplored. Here we evaluate the influence of filtration, air exchange rates, and the fraction of outdoor air on the probability of infection using the well-known well-mixed modeling approach for a multizone. We find filtration lowers the concentration and probability of infection in both source and connected rooms provided at least some air is recirculated, but that probability is not zero. Filtration has no influence without recirculation or unless the outdoor air contains virus. We find that increasing the air exchange rate removes virus from the source room faster but also increases the rate of exposure to connected rooms. Therefore, slower air exchange rates reduce infectivity in connected rooms at shorter durations, but higher air exchange rates reduce infectivity at longer durations. We further find that when outdoor air is virus free, increasing the fraction of outdoor air is helpful, but, when outdoor air is infective, pathogen exposure inside can persist for hours after a short-term release.
60 APPLIED LIFE SCIENCES↗
A multiscale model of the action of a capsid assembly modulator for the treatment of chronic hepatitis B
Chronic hepatitis B virus (HBV) infection is strongly associated with increased risk of liver cancer and cirrhosis. While existing treatments effectively inhibit the HBV life cycle, viral rebound frequently occurs following treatment interruption. Consequently, functional cure rates of chronic HBV infection remain low and there is increased interest in a novel treatment modality, capsid assembly modulators (CAMs). Here, we develop a multiscale mathematical model of CAM treatment in chronic HBV infection. By fitting the model to participant data from a phase I trial of the first-generation CAM vebicorvir, we estimate the drug’s dose-dependent effectiveness and identify the physiological mechanisms that drive the observed biphasic decline in HBV DNA and RNA, and mechanistic differences between HBeAg-positive and negative infection. Finally, we demonstrate analytically and numerically that the relative change of HBV RNA more accurately reflects the antiviral effectiveness of a CAM than the relative change in HBV DNA.
59 BASIC BIOLOGICAL SCIENCES↗
NASA Astronaut Urinary Conditions Associated with Spaceflight
INTRODUCTION: Spaceflight is associated with many factors which may promote kidney stone formation, urinary retention, and/or Urinary Tract Infection (UTI). According to ISS mission predictions supplied by NASA's Integrated Medical Model, kidney stone is the second and sepsis (urosepsis as primary driver) the third most likely reason for emergent medical evacuation from the International Space Station (ISS). METHODS: Inflight and postflight medical records of NASA astronauts were reviewed for urinary retention, UTI and kidney stones during Mercury, Gemini, Apollo, Mir, Shuttle, and ISS expeditions 1-38. RESULTS: NASA astronauts have had 7 cases of kidney stones in the 12 months after flight. Three of these cases occurred within 90 to 180 days after landing and one of the seven cases occurred in the first 90 days after flight. There have been a total of 16 cases (0.018 events per person-flights) of urinary retention during flight. The event rates per mission are nearly identical between Shuttle and ISS flights (0.019 vs 0.021 events per person-flights). In 12 of the 16 cases, astronauts had taken at least one space motion sickness medication. Upon further analysis, it was determined that the odds of developing urinary retention in spaceflight is 3 times higher among astronauts who took promethazine. The female to male odds ratio for inflight urinary retention is 11:14. An astronaut with urinary retention is 25 times more likely to have a UTI with a 17% infection rate per mission. There have been 9 reported UTIs during spaceflight. DISCUSSION: It is unclear if spaceflight carries an increased post-flight risk of kidney stones. Regarding urinary retention, the female to male odds ratio is higher during flight compared to the general population where older males comprise almost all cases due to prostatic hypertrophy. This female prevalence in spaceflight is even more concerning given the fact that there have been many more males in space than females. Terrestrial medications with a known side effect of urinary retention are also associated with urinary retention during flight. However, not all cases of urinary retention surrounded medication use inflight. It is also known that UTI is a terrestrial cause of urinary retention. Furthermore, the treatment of urinary retention with a urinary catheter may be more likely to initiate a UTI in space than on the ground, as aseptic techniques can be particularly challenging with an inexperienced provider in a free-floating environment. Inflight urinary retention and UTI have proven to be highly associated and urinary risks should be considered collectively when planning for space flight.
Law, Jennifer↗
A novel candidate hepatitis C virus genotype 4 subtype identified by next generation sequencing full-genome characterization in a patient from Saudi Arabia
Background and aim: Hepatitis C virus (HCV) infection is a major global public health concern, being a leading cause of chronic liver diseases such as chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The virus is classified into 8 genotypes and 93 subtypes, each displaying distinct geographic distributions. Genotype 4 is the most predominant in the Middle East and Eastern Mediterranean and is associated with high rates of hepatitis C infection worldwide. This study used next-generation sequencing to fully characterize the HCV genome and identify a novel subtype within genotype 4 isolated from a 64-year-old Saudi man diagnosed with hepatitis C. Methods: We analyzed the complete genome of the 141-HCV isolate using whole-genome sequencing. Results: Our phylogenetic reconstructions, based on the entire genome of HCV-4 strains, revealed that the 141-HCV isolate formed a distinct group within the genotype 4 classification, providing valuable new insights into the variability of HCV. Conclusion: This discovery of a previously unclassified HCV subtype within genotype 4 sheds light on the ongoing evolution and diversity of the virus. Such knowledge has significant implications for diagnostic and therapeutic approaches, as different subtypes may exhibit varying drug sensitivities and resistance profiles.
60 APPLIED LIFE SCIENCES↗
Mercury and Radiocesium Accumulation and Associations With Sublethal Endpoints in the Florida Green Watersnake ( Nerodia floridana )
Mercury (Hg) and radiocesium ( 137 Cs) are well-known environmental contaminants with the potential to impact the health of humans and wildlife. Snakes have several characteristics conducive to studying environmental contamination but have rarely been included in the monitoring of polluted sites. We investigated the bioaccumulation of Hg and 137 Cs and associations with sublethal effects (standard metabolic rate [SMR] and hemoparasite infections) in Florida green watersnakes (Nerodia floridana). We captured 78 snakes from three former nuclear cooling reservoirs on the US Department of Energy's Savannah River Site in South Carolina (USA). For captured snakes, we (1) determined whole-body 137 Cs, (2) quantified total Hg (THg) using snake tail clips, (3) conducted hemoparasite counts, and (4) measured the SMR. We used multiple regression models to determine associations among snake body size, capture location, sex, tail THg, whole-body 137 Cs, Hepatozoon spp. prevalence and parasitemia, and SMR. Average whole-body 137 Cs (0.23 ± 0.08 Becquerels [Bq]/g; range: 0.00–1.02 Bq/g) was correlated with snake body size and differed significantly by capture site (Pond B: 0.67 ± 0.05 Bq/g; Par Pond: 0.10 ± 0.02 Bq/g; Pond 2: 0.03 ± 0.02 Bq/g). Tail THg (0.33 ± 0.03 mg/kg dry wt; range: 0.16–2.10 mg/kg) was significantly correlated with snake body size but did not differ by capture site. We found no clear relationship between SMR and contaminant burdens. However, models indicated that the prevalence of Hepatozoon spp. in snakes was inversely related to increasing whole-body 137 Cs burdens. Our results indicate the bioaccumulation of Hg and 137 Cs in N. floridana and further demonstrate the utility of aquatic snakes as bioindicators. Furthermore, our results also suggest a decrease in Hepatozoon spp. prevalence related to increased burdens of 137 Cs. Although the results are intriguing, further research is needed to understand the dynamics between 137 Cs and Hepatozoon spp. infections in semiaquatic snakes.
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
The application of synthetic antibacterial minerals to combat topical infections: exploring a mouse model of MRSA infection
Abstract The development of new antibiotics has stalled, and novel strategies are needed as we enter the age of antibiotic resistance. Certain naturally occurring clays have been shown to be effective in killing antibiotic resistant bacteria. However, these natural clays are too variable to be used in clinical settings. Our study shows that synthetic antibacterial minerals exhibit potent antibacterial activity against topical MRSA infections and increase the rate of wound closure relative to controls. The antibacterial minerals maintain a redox cycle between Fe 2+ /Fe 3+ and the surfaces of pyrite minerals, which act as a semiconductor and produce reactive oxygen species (ROS), while smectite minerals act as a cation exchange reservoir. Acidic conditions are maintained throughout the application of the hydrated minerals and can mitigate the alkaline pH conditions observed in chronic non-healing wounds. These results provide evidence for the strategy of ‘iron overload’ to combat antibiotic resistant infections through the maintained release of Fe 2+ and generation of ROS via distinct geochemical reactions that can break the chronic wound damage cycle.
58 GEOSCIENCES↗
Quantification of Ebola virus replication kinetics in vitro
Mathematical modelling has successfully been used to provide quantitative descriptions of many viral infections, but for the Ebola virus, which requires biosafety level 4 facilities for experimentation, modelling can play a crucial role. Ebola virus modelling efforts have primarily focused on in vivo virus kinetics, e.g., in animal models, to aid the development of antivirals and vaccines. But, thus far, these studies have not yielded a detailed specification of the infection cycle, which could provide a foundational description of the virus kinetics and thus a deeper understanding of their clinical manifestation. Here, we obtain a diverse experimental data set of the Ebola virus infection in vitro, and then make use of Bayesian inference methods to fully identify parameters in a mathematical model of the infection. Our results provide insights into the distribution of time an infected cell spends in the eclipse phase (the period between infection and the start of virus production), as well as the rate at which infectious virions lose infectivity. We suggest how these results can be used in future models to describe co-infection with defective interfering particles, which are an emerging alternative therapeutic.
59 BASIC BIOLOGICAL SCIENCES↗