Antibody response dynamics following Ebola vaccination remain incompletely understood, particularly regarding the continuum of initial induction to long-term persistence. This study developed a mechanistic model of B-cell stimulation post-vaccination able to infer antigen presentation kinetics and propose an identifiable model based solely on anti-ZEBOV IgG levels.
This study was based on...
The COVID-19 pandemic highlighted the importance of understanding coronavirus
evolution and transmission dynamics. However, the evolutionary dynamics of
seasonal human coronaviruses (hCoVs) are less well-characterised. Here, we use a
phylodynamic approach to compare the spread of four seasonal hCoVs (OC43,
HKU1, NL63, and 229E) over ten years within Slovenia. The four...
Phylodynamics bridges the gap between classical epidemiology and pathogen genome sequence data by estimating epidemiological parameters from time-scaled pathogen phylogenetic trees. The models used in phylodynamics typically assume that the sampling procedure is independent between infected individuals. However, this assumption does not hold for many epidemics, in particular for such sexually...
Sequence data, such as nucleotides or amino acids, is essential for understanding biology. However, analyzing sequencing data and genotype-phenotype associations is challenging due to noise, nonlinear relationships, collinearity, and high dimensionality. While machine learning (ML) effectively detects patterns in this data, user-friendly tools remain limited. To address this, we developed...
A major determinant for anti-poliovirus immune response is the viral capsid protein VP1. Multiple unexpected amino acid changes within this protein have been identified in wildtype type 1 poliovirus (WPV1) circulating in Pakistan following the removal of type 2 poliovirus from the oral poliovirus vaccine. These amino acid changes map to known antigenic sites as well as a conserved region found...
The molecular clock is a statistical tool that we use to infer evolutionary rates and timescales from molecular sequence data, with the use of calibrations. These calibrations can include sequences sampled at different points in time for many organisms. Without calibrations, evolutionary rates and times are jointly unidentifiable and thus are required. Before inferring rates and times, it is...
Background: There is a pressing need to monitor the circulating strains and the emergence of novel HIV-1 variants in the country, especially in the understudied South-south regions. Thus, this study aimed to characterize the genetic diversity of HIV-1, tropisms, and drug-resistant mutations (DRMs) among HIV-infected individuals in the region.
Methods:
One hundred and six HIV-infected...
Understanding transmission clusters is essential to uncovering the dynamics of viral
epidemics, identifying outbreak drivers, and guiding effective public health responses. Cluster
analysis combines genomic and epidemiological data to trace transmission pathways and
generate actionable insights to curb disease spread.
ClusterFinder, developed within the EU-funded SEQ4EPI project, is a...
The increasingly widespread application of next-generation sequencing (NGS) in clinical diagnostics and epidemiological research has generated a demand for robust, fast, automated, and user-friendly bioinformatics workflows. To guide the choice of tools for the assembly of full-length viral genomes from NGS datasets, we assessed the performance and applicability of four open-source...
Effective viral transmission network analysis is crucial for controlling virus spread. Cluster size is key for prioritizing interventions. Traditional methods often miss network extent due to sampling biases. This study investigates mean pairwise genetic distance (MGEND) as a proxy for estimating "true" cluster size.
Viral samples from an HIV clinic in Mexico City were classified into...
Respiratory Syncytial Virus (RSV) is a single-stranded RNA virus that most people encounter as children. RSV infection generally manifests with mild, cold-like symptoms, but can cause severe complications in immunocompromised populations such as infants, the elderly, and immunosuppressed transplant patients. These
Despite its global impact, epidemiological surveillance of RSV in Switzerland...
Timed viral phylogenies are often used to understand geographic movements, past population dynamics, the emergence of new lineages and epidemic dynamics. These inferences are frequently done in a framework using coalescent theory. Exchangeability in coalescent theory refers to the property that each pair of lineages is equally likely to coalesce, moving back in time from the present to the...
The high species richness of bats (> 1400 species) is mirrored by the diversity of viral families they harbor. It is likely that SARS-CoV-2, a Betacoronavirus Sarbecovirus responsible for the COVID-19 pandemic, originated in Rhinolophus spp. bats. In this context, it is critical to understand the origins of Sarbecovirus diversity in wildlife and the mechanisms that favor their emergence in...
Marek’s disease (MD) provides a well-documented model for researching imperfect vaccines and viral vaccine escape dynamics. Despite more than 50 years of vaccination programmes, MD remains prevalent worldwide in the chicken industry. The vaccines are “leaky”, allowing low level persistence and transmission of Marek’s disease virus (MDV), the causative oncogenic herpesvirus. Resistance has...
Background: Rotavirus remains a leading cause of severe gastroenteritis in children under five, particularly in low- and middle-income countries (LMICs). In Malawi, G9P[6] strains re-emerged in 2017, five years after the introduction of Rotarix rotavirus vaccine, necessitating an in-depth investigation of their genetic diversity, evolutionary origins, and public health...
Wastewater monitoring of pathogens offers the potential to track a wide range of infectious diseases for public health, but current methods for analyzing transmission dynamics are primarily tailored to SARS-CoV-2, which is detected at high concentrations in municipal sewage. To support robust surveillance of pathogens with lower concentrations in wastewater and limited clinical validation...
Although antiretroviral therapy (ART) can effectively suppress HIV replication, infection cannot be eliminated due to the presence of long-lived, latently infected cells. Treatment interruption leads to the reactivation of latently infected cells and subsequent viral replication in plasma, which may replenish the population of long-lived latently infected cells. Understanding the timing of...
The serial interval of an infectious disease – the length of time between symptom onset of an infector and infectee – is an important quantity in epidemiology, but its estimation requires knowledge of individuals' contacts and exposures, typically obtained through resource-intensive contact tracing efforts or household studies. Under partially sampled data, purported transmission pairs...
Influenza A viruses (IAVs) remain a significant public health threat due to their ability to jump between host species, as demonstrated by the H1N1 pandemic in 2009. Despite increased genomic surveillance, knowledge of the evolutionary dynamics allowing such zoonotic events is still limited, and the genetic markers that facilitate transmission between humans and swine remain unclear. To...
Dengue fever is the most important arbovirosis for public health, with more than 6 million cases worldwide in 2023. The virus is present in the subtropical and tropical regions of the world often in co-circulation with over arboviroses. There is currently no effective treatment commercially available. Mosnodenvir is the first anti-dengue compound with very high preclinical pan-serotype...
Despite intensive study, surprising gaps remain in our knowledge of transmission patterns during the COVID-19 pandemic, particularly transmission as new lineages emerge. We analyzed 134,785 SARS-CoV-2 genomes from 7 lineages collected in Massachusetts from November 1, 2021, to January 17, 2023; this includes 85,125 genomes with individualized epidemiological data across 666 testing facilities....
A characteristic feature of HIV-1 is its ability to develop a diverse population that can adapt to hostile environments. The source of this diversity is often attributed to its high mutation rate, estimated to be around 5.0x10-5 mutations per site per round of replication (mut/site/rep). However, there is high variation in the observed mutation rates across published studies. It remains...
Phylodynamic analyses infer epidemiological parameters from pathogen genome sequences for enhanced genomic surveillance in public health. Pathogen genome sequences and their associated sampling dates are essential data in every analysis. However, sampling dates are usually associated with hospitalisation or testing and can sometimes be used to identify individual patients, posing a threat to...
In an HIV-1 molecular epidemiology study in Spain, based on maximum likelihood (ML) phylogenetic analyses of protease-reverse transcriptase (PR-RT) sequences, we identified a cluster of 46 individuals from 8 regions not grouping with references of known subtypes or CRFs, which through analyses with Recombination Identification Program (RIP), bootscanning, and trees of partial fragments, was...
Viral "blips" are single timepoint episodes with detectable plasma HIV-1 RNA preceded and followed by undetectable viremia in individuals on antiretroviral therapy (ART). Despite their common occurrence, the origin, biological implications, and clinical consequences of viral blips for people with HIV (PWH) remain unclear. Proposed explanations include intermittent viral release from latent...
SARS-CoV-2 has undergone repeated and rapid evolution to circumvent host immunity.However, outside of prolonged infections in immunocompromised hosts, within-host positive selection has rarely been detected. The low diversity within-hosts and strong genetic linkage among genomic sites make accurately detecting positive selection difficult. Longitudinalsampling is a powerful method for...
Despite the success of antiretroviral therapy (ART) in controlling viremia, HIV-1 reservoirs persist during therapy constituting the major obstacle to a functional cure. These reservoirs lead to a rapid rebound in viremia when treatment fails or is discontinued. To eliminate this viral reservoir that mostly resides in tissues, it is key to characterize its tissue microenvironment and...
Background: Case reporting in a pandemic or for emerging viral infections depends heavily on testing strategies and as a result the degree of under-reporting of true incidence can vary substantially. We previously developed GInPipe [1], a computational tool that allows estimation of under-reporting levels over time from time-stamped pathogen genome surveillance data, within a few minutes...
Climate change and globalization are expected to increase the frequency of infectious disease outbreaks, underscoring the need for reliable forecasting methods to inform decision-making. The COVID-19 pandemic highlighted significant limitations in forecasting accuracy, particularly in scenarios where episodic selection drives the emergence of new genetic variants—such as the Delta and Omicron...
Background:
This study was aimed to understand the evolutionary and transmission dynamics of HIV-1 epidemic in Serbia and to reveal the socio-demographic and clinical factors that shaped the expansion of phylogenetic transmission clusters. The dataset of 720 HIV-1 pol sequences isolated from both newly diagnosed and therapy experienced healthcare clients, between 1997 and the end of 2023, was...
HIV-1 transmission leads to lifelong infection marked by continuous viral evolution and evasion of host immunity. The specifics of this host-pathogen interaction, including the complex dynamics of transmission, quasispecies diversity, and viral recombination rate, remain unclear. To better characterize these dynamics in vivo, we engineered doubly barcoded viral libraries of three HIV-1 strains...
Lassa fever, caused by the Lassa virus (LASV), has led to numerous fatalities in West Africa and cases exported intercontinentally since its discovery in 1969. Currently, there are no approved vaccines, with recent research focusing on immunotherapy. Lassa virus is grouped into different lineages that circulate in specific geographical areas, elicit varying immune responses, and display...
Antibody (Ab) accessible sites at the surface of Env include the most variable HIV-1 sites. Different patterns of Ab recognition and neutralization are observed within and between HIV-1 clades. Predicting the functional effect of epitope diversity on Ab sensitivity is important for designing population-specific prophylactic strategies. We developed a statistical framework that incorporates...
Mathematical modelling allows us to answer “if this then what” questions. For infectious disease epidemiology this has been widely used to guide interventions: if we intervene like this, how much disease will we prevent? Also important, though much less widely practised, is the use of mathematical modelling to guide the design of studies and trials: if we measure like this, how much will we...
Persistence of HIV in people living with HIV (PWH) on suppressive antiretroviral therapy (ART) has been linked to physiological mechanisms of CD4+ T cells. We summarize this concept with the “passenger hypothesis”, that most persistence of the HIV reservoir during ART is due to cellular vs viral mechanisms. In order to determine which mechanisms are most important for persistence, and thus...
The discovery of very potent, broadly neutralizing antibodies (bnAbs) against HIV-1 has revived the hope for new treatment and prevention methods against the virus. Nevertheless, several clinical trials have shown that the breadth of such bnAbs is still limited by viral resistance. Here, we explore whether currently available neutralization
datasets on bnAbs predicted to bind similar epitopes...
A key question in evolutionary epidemiology is to determine differences in the conditions that may allow some mutant strains to spread in a population where a resident strain is already circulating. Evolutionary invasion analyses assume that the immunity is long-lasting for previously infected individuals making it difficult to study straits such as immune escape. We relax this last assumption...
Background:
Persistent SARS-CoV-2 infections in immunocompromised individuals are often associated with key features of viral evolution, including accelerated mutation rates, emergence of novel variants of concern (VOCs), cryptic lineages, reservoirs of antiviral resistance, super-spreading events and interspecies transmission. These patients represent a critical group for the...
Bayesian phylogeographic inference is a powerful tool in molecular epidemiological studies, enabling the reconstruction of the dispersal history of rapidly evolving pathogens. BEAST, a Bayesian phylogenetic inference software package, provides a discrete trait analysis (DTA) that integrates geographic information as discrete characters and infers transition events among discrete sampling...
Endogenous Viral Elements (EVEs) originate when viruses integrate their genetic material into the host genome, becoming a permanent part of the host’s DNA. As molecular fossils of ancient viral infections, EVEs offer valuable insights into host-virus coevolution and virus diversity over evolutionary timescales.
We aim to detect EVEs across 948 mammalian genomes by performing a nested...
Jingmenviruses are understudied flavi-like viruses with a segmented genome. They have been detected worldwide in a wide range of hosts, such as arthropods including ticks and vertebrates including cattle and humans with febrile illness symptoms. As next-generation sequencing has become more affordable, increasing numbers of large-scale metagenomics studies have been published, alongside raw...
Molecular epidemiology of hepatitis A virus (HAV) plays a critical role in identifying outbreak origin and conducting surveillance. Although it is mostly carried out using short partial VP1/2A genomic sequences, utilizing whole-genome sequences (WGS) provides more accurate and robust information. In Argentina, where HAV vaccination is mandatory since 2005, the local sequence information is...
Unlike other areas of modern statistical inference, genomic epidemiology lacks theory to guide decisions about how to sample pathogen genomes. This makes it difficult to answer even simple questions about how sampling choices impact the quality of inferences drawn from genomic data. Researchers therefore often resort to sampling opportunistically, leading to inefficient and unrepresentative...
The sharing of viral genomic data is critical for scientific research and public health responses. While platforms like the International Nucleotide Sequence Database Collaboration (INSDC: NCBI, ENA, DDBOJ) and GISAID facilitate data sharing, challenges remain in meeting the specific needs of the pathogen genomics community. Persistent concerns about data misuse, “scooping,” and limitations on...
Five years since the start of the pandemic, SARS-CoV-2 remains a leading cause of acute respiratory infections, despite most people having been infected at least once. Unprecedented levels of global genomic surveillance provide a rich basis for understanding how SARS-CoV-2 variants continue to evolve in the post-Omicron era, a critical topic for vaccine strain updates.
Using insights...
Background
In 2022, an Mpox clade II outbreak affected many countries including Slovenia. To optimize control, it is important to know the extent by which such outbreaks are driven by introductions from abroad or by within-country transmission. We used sequences of all Slovenian cases in a phylodynamic model to address this question, and investigated the potential to assess the number of...
Singapore faces recurring dengue outbreaks that pose substantial public health and economic burdens, with recent years seeing unprecedented case numbers. While current surveillance systems track case counts, the ability to predict outbreaks in real-time remains challenging. We propose combining real-time estimation of the effective reproduction number (Rₑ) with analysis of viral spread...
Reassortment is the exchange of genomic segments between viruses. It is a significant feature of the evolution of influenza A viruses (IAV), where it can yield new combinations between highly divergent lineages (antigenic shift). In this study, we evaluated the reliability of standard comparative methods for reconstructing reassortment events in the evolutionary history of H5Nx IAV genomes. We...
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a causative agent of several lymphoproliferative diseases, particularly in immunocompromised individuals. These malignancies often originate from latently infected B cells, where KSHV persists as extrachromosomal, circularized episomes. While the viral protein LANA is essential for viral maintenance during latency, the mechanisms enabling...
The COVID-19 pandemic has caused over 776 million cases and 7 million deaths globally, highlighting the need for predictive tools to anticipate SARS-CoV-2 evolution. The S1 subunit of the Spike glycoprotein, essential for viral entry into human cells, undergoes frequent mutations that influence transmissibility and immune evasion. Predicting such mutations could be crucial for the development...
The COVID-19 pandemic has caused over 776 million cases and 7 million deaths globally, highlight-ing the need for predictive tools to anticipate SARS-CoV-2 evolution. The S1 subunit of the Spike glycoprotein, essential for viral entry into human cells, undergoes frequent mutations that influence transmissibility and immune evasion. Predicting these mutations is crucial for developing vaccines...
Background: Ever since the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-COV-2) which caused COVID-19 disease began to spread, the globe has been dealing with an unparalleled public health calamity. The entire health system is under strain as a result of the pandemic. Above all, microbiologists have experienced significant challenges in terms of diagnosis. The intriguing part that was...
Background
The COVID-19 pandemic has highlighted the need for real-time infectious disease surveillance and forecasting systems to identify trends in transmission. In this study, we compare short-term forecasting models for COVID-19 hospital admissions that make predictions 1 to 4 weeks ahead based on retrospective electronic health record data from the Bern region of...
High-Throughput Single-Genome Amplification and Sequencing (HT-SGS) enables detailed measurements of intra-host virus genotypes via barcoding of individual virus genomes during reverse transcription (RT) followed by PCR amplification, sequencing, and bioinformatic error correction procedures. However, the absence of “ground-truth” RNA reference samples makes it challenging to evaluate...
During infection, human immunodeficiency virus (HIV) maintains a stably integrated reservoir of proviruses that persist within the host genome despite combined antiretroviral therapy (cART). Characterizing these reservoirs remains challenging due to insufficient phylogenetic resolution, particularly under cART, which limits our ability to assess proviral integration and replication competency...
Spillover of infectious diseases is a significant issue for human, animal, and plant health, in part due to their potential to establish in the new host population, thus achieving a host jump. Current approaches to predict and prevent host jumps are structured around discovering new viruses, drawing associations between pathogen characteristics and host jump risk, and managing spillover, but...
Selection pressures on SARS-CoV-2 molecular phenotypes have changed dramatically in time since the virus’s emergence. Initially, for example, the greatest pressure was on enhancing the virus's intrinsic biological traits in order to increase its transmissibility in the naive population. Then, as population immunity grew from previous infections and vaccination, immunity became the primary...
Insertions and deletions (indels) have appeared frequently during SARS-CoV-2 evolution, including as lineage defining mutations. However, indels are difficult to study, particularly at the within-host level, due to differing processes of alignment and consensus genome generation, making it difficult to evaluate their evolutionary significance and compare between individuals. We have developed...
A widespread outbreak of H5N1 avian influenza A virus was detected in U.S. dairy cattle in 2024, causing significant illness in cattle, reduced milk production, and economic damage. We analyze 537 H5N1 genomes from birds and non-human mammals leading up to the emergence of H5N1 in cattle, and 1,739 genomes from cattle, poultry, humans, and other mammals involved in the 2024 outbreak for which...
HIV-1 has nine main subtypes that persist in infected populations; however, the overall diversity of HIV-1 is much larger due to recombination amongst these original subtypes. Recombination has led to many unique recombinant forms and over 100 circulating recombinant forms (CRFs), which may become more prevalent than the two parent strains in a given region. We analysed sequences taken from...
RNA viruses like SARS-CoV-2 have a high mutation rate, which contributes to their rapid evolution. The rate of mutations depends on the mutation type (e.g., A→C, A→G, etc.) and can vary between sites in the viral genome. Understanding this variation can shed light on the mutational processes at play, and is crucial for quantitative modeling of viral evolution. Using the millions of available...
The HIV epidemic in the Former Soviet Union (FSU) is growing rapidly, with 140,000 new infections reported in 2023, marking a 20% increase since 2010. Despite ongoing efforts to expand HIV prevention and treatment programs, AIDS-related deaths are on the rise in this region, underscoring the need for a better understanding of transmission dynamics and drug resistance mutations (DRMs) to inform...
The measles virus, renamed Morbillivirus hominis in 2023 (Paramyxoviridae), is subjected to a global elimination program established by the World Health Organization since 2012. However, despite these efforts, two significant epidemic resurgences occurred in France (2008-2012 ; 2017-2019). Based on a rich collection of samples, this work illuminates the evolutionary dynamics of...
HCoV-OC43 is a common cold coronavirus that has persisted in the human population for decades. This study investigates HCoV-OC43's genomic diversity and recombination patterns to elucidate the emergence of new genotypes and shed light on intra-host diversification, which underpins the ongoing evolution of HCoV-OC43. Employing consensus sequencing and high-throughput single genome sequencing...
Tree metrics are measures to compare the similarity between two tree topologies. Effective sample size (ESS) is a statistic that quantifies the amount of autocorrelation in Markov chain Monte Carlo (MCMC) and is used to assess run convergence. With tree metrics, Lanfear et al showed that we can compute an ESS for tree topologies. From the plethora of tree metrics that have been developed,...
Epidemiological models are key tools for understanding infectious disease dynamics. Traditional SIR models assume that all individuals in a host population are initially susceptible, limiting their ability to predict complex outbreak patterns observed in real-world epidemics. Here, we introduce the USIR model, which incorporates the concept of evolutionary niche expansion—an adaptation of...
Human papillomavirus (HPV) infections drive one in twenty new cancer cases,
exerting a particularly high burden on women. Most anogenital HPV infections are
cleared in less than two years, but the underlying mechanisms that favour persistence
in around 10% of women remain largely unknown. Notwithstanding, it is precisely this
information that is crucial for improving treatment, screening...
Whether or not there is a limit to adaptation is one of the fundamental questions of evolutionary biology. To what degree can a viral population evolve to be fitter in a constant environment? In a long-term evolution experiment with HIV-1 in two T-cell lines (MT-2 and MT-4), we have been observing the accumulation of majority mutations and fixations at an almost constant rate for more than...
BACKGROUND: Modelling HIV evolution can illuminate mechanisms of viral persistence and predict resistance to antiretroviral therapies. However, current models do not take into account viral population size. Here, we examine in a large cohort of simian-human immunodeficiency virus (SHIV) infected rhesus macaques the relationship between viral population size and rates of virus...
Human endogenous retroviruses (HERVs) comprise about 8% of our genome and provide us with a valuable fossil record of host-retrovirus interaction in our primate ancestors. The most recently active HERV-K(HML-2) 5Hs group, although now apparently extinct as an infectious agent, has some members that entered our ancestral genome less than 1 million years ago and retain one or more viral ORFs,....
Influenza A virus (IAV) has placed a significant strain on public health systems by causing seasonal outbreaks and, in severe cases, pandemics. This burden is compounded by its rapid evolution, which drives immune escape and requires the frequent redesign of vaccines and antiviral drugs. Therefore, genomic surveillance of IAV is crucial for monitoring its evolution and informing vaccine and...
Respiratory syncytial virus (RSV) is a highly contagious, enveloped, single-stranded RNA respiratory virus that primarily causes mild, cold-like symptoms. However, it can lead to severe illness, hospitalization, or death in infants and immunocompromised individuals. RSV is classified into two subtypes, RSV-A and RSV-B, with one subtype typically dominating a given season that begins in the...
Background: In 2022, Thailand lifted lockdown and isolation measures, and SARS-CoV-2 was declared endemic by the Ministry of Public Health. The spread of the Omicron variant raised questions about the relative contributions of community versus household transmission to ongoing infections. We analyzed SARS-CoV-2 transmission within the Thailand VERDI-RECOVER study and conducted whole genome...
