Understanding the forces driving intra-host HIV to evolve resistance to interventions is critical for designing effective countermeasures. While genetic linkage patterns are potentially a powerful tool to quantify the relative contributions of multiple evolutionary forces (mutation, recombination, selection), the severe population bottlenecks accompanying therapy confound these signatures. To...
There are substantial differences between patterns of genetic similarity clusters seen in HIV epidemics of the Global North and Southern Africa, prompting questions about factors contributing to these differences. Unlike patterns observed in the Global North, Southern African epidemics contain lower clustering rates and a scarcity of large clusters.
Here we describe an exploration of...
One way of finding new features of biological importance in an organism is to find regions where its genetic sequence has unexpectedly high conservation, signifying that deviations from the conserved sequence affect ability to produce viable progeny. Many methods implementing this approach carry an implicit assumption that each locus in a sequence should be treated equally. But, in fact,...
Hepatitis C virus (HCV), which affects about 58 million people, is classified into 8 genotypes and >90 subtypes. Genotypes differ at >30-35% of nucleotide positions while subtypes within a genotype differ at 15-25% of positions. While most subtypes can be cured by direct-acting antivirals, some are resistant to treatment. The Antiviral Unit at the UK Health Security Agency established a...
Introduction:
Since 2015, the veSEQ method, a bait-capture metagenomic sequencing technique, has advanced HIV genomic research via the PANGEA consortium and is being adopted in Uganda, Botswana, and Zambia. Notable for its affordability and high-throughput capability in sequencing diverse genomes, veSEQ shows promise for HIV drug resistance monitoring and pathogen studies. High...
Astroviruses comprise a genetically diverse viral family linked to diseases in both humans and birds, resulting in substantial health impacts and economic burdens. Traditionally classified into Avastrovirus and Mamastrovirus genera based on host species, next-generation sequencing has revealed broader transmission patterns, necessitating a reevaluation of the current classification approach....
Through antigenic evolution, viruses like seasonal influenza evade recognition by neutralizing antibodies elicited by previous infection or vaccination. This means that a person with antibodies well-tuned to an initial infection will not be protected against the same virus years later and that vaccine-mediated protection will decay. It is not fully understood which of the many endemic human...
Background: Respiratory Syncytial Virus (RSV) is a leading cause of acute respiratory tract infection, with greatest impact on infants, immunocompromised individuals, and older adults. RSV prevalence decreased substantially following the implementation of non-pharmaceutical interventions to mitigate the SARS-CoV-2 pandemic but later rebounded with initially abnormal seasonality. The biological...
Genomic surveillance of poliovirus will prove critical to the next phase of the eradication effort and relies on fast and accurate viral detection. With direct sequencing methods, the time from sample to results has been drastically reduced in relation to previous approaches. The piranha software developed within our group provides a framework for analysing high throughput sequencing data from...
Combinational antiretroviral therapy (cART) is the most effective tool to prevent and control HIV-1 infection without an effective vaccine. However, HIV-1 drug resistance mutations (DRMs) and naturally occurring polymorphisms (NOPs) can abrogate cART efficacy. Here, we aimed to characterize the HIV-1 pol mutation landscape in Cameroon, where highly diverse HIV clades circulate, and identify...
Wastewater samples collected at municipal wastewater treatment plants have become a promising source of data to complement traditional infectious disease surveillance. In addition to measuring pathogen concentrations in wastewater over time to monitor transmission dynamics, viral RNA sequencing has been used to investigate the genetic diversity of SARS-CoV-2 and track the emergence and...
Widespread surveillance, rapid detection and appropriate intervention will be critical for successful eradication of poliovirus. With deployable next-generation sequencing (NGS) approaches, the time from sample to result can be significantly reduced compared to cell culture and Sanger sequencing. We developed [piranha][1] (poliovirus investigation resource automating nanopore haplotype...
Bayesian phylodynamic analyses are complex and often complicated to execute which presents barriers to automation in public health contexts, where swift and reliable analyses are essential. This talk introduces Snk, a Snakemake workflow management system designed to facilitate the installation of Snakemake workflows as dynamically generated Command Line Interfaces. It will explore how the Snk...
Accurately reconstructing the transmitted/founder virus of an HIV infection is challenging. It is particularly difficult to do with heterochronous sequences such as proviruses persisting on ART, because of the challenge of determining an appropriate root position that represents the ancestor. However, since proviral sequences are archived throughout untreated HIV infection and persist...
Bayesian phylodynamic analysis of genomic datasets has been key for elucidating the evolutionary and transmission dynamics of pathogens. However, topological convergence of these analyses on large viral datasets has not been comprehensively assessed. By carefully re-running and analyzing 15 classic large phylodynamic analyses we show that that: 1) convergence and mixing issues are widespread...
The SARS-CoV-2 pandemic was an important example of how the spillover of a novel virus can go from a localised outbreak to a global pandemic in weeks. In the early stages of an outbreak, information is scarce and what's available can be exceedingly valuable. Experimental data is time-consuming to produce and is often not available until much later stages of an outbreak
Protein language...
About 25% of HIV-1 infections are initiated by multiple founder variants based on HIV-1 sequencing via single genome amplification (SGA). Infections with multiple HIV-1 variants are associated with poorer clinical outcomes. Compared to SGA, deep-sequencing platforms offer high resolution to study within-host genetic diversity. We investigated the genetic characteristics of HIV-1 populations...
Background: Understanding the determinants of SARS-CoV-2 transmission is pivotal to inform control efforts. As transmission events aren’t observed, this remains challenging. Pathogen sequences can provide insights into the proximity of infections within a transmission chain. Phylogeographic approaches have helped characterize epidemic spread. However, they can produce biased results when...
Evidence suggests that persistent SARS-CoV-2 infections may contain long periods of replicating virus, creating potential viral reservoirs of high genetic diversity. An earlier analysis of SARS-CoV-2 viral sequence data from >38,000 samples collected at the Houston Methodist Medical Center identified individuals who were sampled repeatedly. This dataset was used to conduct a longitudinal...
Molecular sequence data from rapidly evolving organisms are often sampled at different points in time. Sampling times can then be used for molecular clock calibration. The root-to-tip (RTT) regression is an essential tool to assess the degree to which the data behave in a clock-like fashion. We introduce Clockor2, a client-side web application for conducting RTT regression...
<span class="s1">Generation intervals are distributions that describe the time between infection and onward transmission. They are a key epidemiological quantity because, together with the basic reproduction number R</span><span class="s2">0</span><span class="s1">, they determine the population-level growth rate of a pathogen r and its doubling...
Preexposition prophylaxis (PrEP) was approved for use in the Spanish National Health System in late November 2019. We examined whether PrEP roll-out had an effect on HIV-1 clustering in Spain. For this study, protease-reverse transcriptase sequences from HIV-1 infections diagnosed in 11 Spanish regions in the years before and after PrEP roll-out were analyzed with an approximate maximum...
Nipah virus is a highly pathogenic bat-borne virus that occasionally spills over into humans. The NiV receptor binding protein (RBP) binds host receptors during cell entry and is a target of neutralizing antibodies, which can protect against disease. Here, we experimentally measure the effects of all amino acid-mutations in the RBP on three viral phenotypes: cell entry, receptor binding, and...
Advances in bacterial biofilm infection research have improved our understanding of antibiotic resistance and immune evasion, which can be explained by social behavior. Biofilms are structured cooperative communities wherein bacterial subpopulations have differing biological roles for biofilm maintenance. Social interactions among structured populations may also play a role in viral evolution...
SARS-CoV-2 is characterized by sequential emergence of highly divergent and highly transmissible variants, denoted as variants of concern (VOCs). In parallel, it has been observed that a subset of patients, who suffer from immunosuppression, develop chronic infections. In some case highly divergent variants emerge in these patients with mutations similar to those in VOCs. The similarity...
Vaccine and viral induced immunity place significant multifarious selective pressures on viruses they target. For SARS-CoV-2, the strength of this selection pressure has been in flux over the course of the pandemic as variant specific vaccine efficacy ranged from 30-95%. Monitoring and understanding antigenic evolution of SARS-CoV-2 is therefore crucial for vaccine optimization. Here,...
Antiviral resistance threatens global health and necessitates innovative approaches for treating infections. One strategy is identifying and targeting viral phenotypes where susceptible viruses exert a dominant effect over their resistant counterparts, mitigating resistance evolution. The candidate poliovirus antiviral pocapavir exhibits this effect in cell culture and mouse models, however,...
The amount of sequence data produced as part of the global pandemic response far outstrips that of previous epidemics. A key question is whether the sequencing and collaboration networks developed to combat a pandemic can be used to monitor localised outbreaks and epidemics. The disruption of typical RSV transmission during the COVID-19 pandemic has renewed interest in a genomic approach to...
The WHO declared mpox a public health emergency of international concern on July 23, 2022. It is still unclear to what extent international travel contributed to the sustained spread of mpox and the degree to which national vaccination campaigns were responsible for controlling the epidemic. We employ phylogeographic and phylodynamic models to jointly analyze mpox genomes from viruses sampled...
Protein-unbound antiretroviral (ARV) drugs in the plasma may either diffuse across the walls of high endothelial venules (HEVs) into the lymph node (LN) parenchyma or be taken up by lymphocytes (naïve T cells) in the bloodstream and transported into the lymph node through cell migration via HEVs. To explore the relative contributions of free and cell-mediated drug trafficking, our...
Botswana, like the rest of the world, has been significantly impacted by SARS-CoV-2. In November 2022, we detected a monophyletic cluster of genomes comprising a sub-lineage of the Omicron variant of concern (VOC) designated as B.1.1.529.5.3.1.1.1.1.1.1.74.1 (alias FN.1; clade 22E). Genomes were from both epidemiologically linked and unlinked samples collected in three close locations in the...
COVID-19 has become endemic, with dynamics that reflect the waning of immunity and re-exposure, by contrast to the epidemic phase driven by exposure in immunologically naïve populations. Endemic does not, however, mean constant. Further evolution of SARS-CoV-2, as well as changes in behaviour and public health policy, continue to play a major role in the endemic load of disease and mortality....
Phylogenetics provides feedback for public health programs’ effectiveness, including for pre-exposure prophylaxis (PrEP), a key pillar to end the HIV epidemic. In British Columbia (BC), PrEP has been provided free of charge since 2018, but eligibility criteria, access barriers, and adherence diminish its potential. We estimated HIV cases in BC averted through PrEP, which we hypothesized were...
Background: In 2019, the National Influenza Centre at the National Institute of Health, Pakistan in collaboration with the World Health Organization implemented dedicated human respiratory syncytial virus (RSV) surveillance in children below the age of two years, which circulation overlaps with that of influenza and other respiratory viruses during the winter months.
Methods: Nasal swabs...
Several SARS-CoV-2 Variants of Concern (VOCs), including Alpha, Omicron, and more recently, BA.2.86/JN.1, are thought to have emerged from chronically infected individuals, including immunocompromised or immunosuppressed individuals. This hypothesis is supported by several lines of evidence: (1) Immediate ancestors of these VOCs have not been sampled; (2) These VOCs exhibited...
Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across metagenomes. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 novel anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus...
Recombination significantly influences the evolutionary dynamics of HIV. A high recombination rate promotes extensive diversity upon which selection can act, while also enabling the purging of deleterious mutations from the viral population. Despite acknowledging the prevalence of recombination, common phylogenetic methods often assume a single evolutionary history. The repercussions on...
In 2019 SARS-CoV-2 emerged as a new human pathogen, giving rise to a pandemic that has resulted in over 700 million cases and 7 million deaths at the time of writing. Understanding the dynamics behind the generation of new variants during a pandemic event is important for improving disease control strategies and public health policies. Even though we now have an unprecedented amount of genomic...
Introduction
Widespread drug resistance to NNRTI-based therapies prompted a shift to INSTI-based combination antiretroviral therapy (cART), essential for the health of individuals living with HIV and global HIV elimination efforts. Our study focuses on low-frequency mutations (LFMs) to understand drug resistance dynamics, utilizing our novel AMPHEUS system with the veSEQ pipeline for...
The rapid evolution of human viruses poses a significant challenge to researchers developing strategies to prevent viral disease. Understanding the impact of viral protein mutations plays a key role in everything from vaccine design to antiviral drug development. Deep mutational scanning (DMS) is an indispensable high-throughput technique for determining the consequences of mutations across...
Visualizing flu substitutions may help identify the features that enable certain clades to succeed as others die out. For example, flu viral escape from prior antibody responses is most likely if mutations are on the virus surface proteins (hemagglutinin, HA, and neuraminidase, NA) and decrease antibody binding. We present a tool, Flu Strain Compare, which maps flu mutations onto 3D HA and NA...
Throughout the pandemic, countries and scientists rushed to predict the impact of sequentially emerging variants by, in part, trying to predict the size of the wave likely to hit their local community. Our study aims to predict the amplitude of forthcoming COVID-19 waves using statistical modelling and a unique global dataset. Utilizing publicly available datasets, we compiled relevant...
A new variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), named Omicron (Pango lineage designation B.1.1.529), was first reported to the World Health Organization by South African health authorities on 24 November 2021. The Omicron variant possesses numerous mutations associated with increased transmissibility and immune escape properties. In November 2021, Mexican...
The SARS-CoV-2 pandemic kept the whole world in suspense for 3 years and is still ongoing. Yet, most countries returned back to normalcy, thanks to broadly available vaccines and less severe symptoms of currently circulating variants.
Nevertheless, the virus is continuously evolving and new variants of concern are emerging, which may develop mechanisms to escape the immune response or...
Human rhinovirus (HRV) is the causative agent of > 50% of cold-like illnesses worldwide and responsible for billions of dollars in economic impact each year due to lost productivity. During the 2020-2023 COVID-19 pandemic, strict isolation measures in the initial six months suppressed HRV infections worldwide. Unlike other non-SARS-CoV-2 respiratory viruses, HRV cases returned to pre-pandemic...
Over the past decade, pathogen genomic surveillance has become a vital public health tool for monitoring and controlling viral outbreaks. Uncoupled from epidemiological data, the public health value of the unprecedented volume of SARS-CoV-2 genomic data is not fully realized. Here, we combine viral genomic and epidemiological data from over 134,000 Massachusetts SARS-CoV-2 genomes tested and...
Molecular data analysis is invaluable in understanding the overall behavior of a rapidly spreading virus population when epidemiological surveillance is problematic. It is also particularly beneficial in describing subgroups within the population, often identified as clades within a phylogenetic tree that represent individuals connected via direct transmission or transmission via differing...
Genomic data is frequently used to understand the transmission and evolutionary dynamics of viral populations. One popular approach is to use phylogenetic trees to reconstruct the past dynamics of viral populations (i.e. ‘phyodynamics’). The availability of tens of millions of SARS-CoV-2 genomic sequences pose unique challenges to this approach because of the high computational cost associated...
Heartland virus (HRTV) is an emerging tick-borne bunyavirus associated with severe febrile illness that has caused >60 cases across the southeastern and midwestern US since its discovery in 2009. Little is known about the transmission ecology and phylodynamics of HRTV and only 13 unique complete HRTV genomes exist in the literature (3 of which were generated by our group). Since our group...
Viral phosphodiesterases (PDEs) are a striking example of how the acquisition of new genes through mechanisms such as horizontal transfer and duplication can shape the interactions between RNA viruses and their hosts. These PDEs, which recurrently arose via horizontal transfer of cellular AKAP7 mRNA into multiple coronavirus subgenera, including MERS-related coronaviruses, inhibit activation...
Background
Acute respiratory infections caused by RSV can be severe, resulting in pediatric hospitalizations and childhood deaths, mostly in developing countries. So here, we investigated the epidemiology and the genetic characteristics of RSV infections among patients hospitalized with severe acute respiratory infections using data from the 2022-2023 sentinel...
We investigated transmission dynamics of a large HIV outbreak among persons who inject drugs (PWID) in Kentucky and Ohio during 2017–2020 by using detailed phylogenetic, network, recombination, and cluster dating analyses. Using polymerase (pol) sequences from 193 people associated with the investigation, we document high HIV-1 diversity, including subtype B (44.6%); numerous circulating...
The use of barcoded SIV allows the tracking of individual viral lineages within infected rhesus macaques. Studies of clonal dynamics early after vaginal infection have demonstrated a surprising diversity in the sizes of founding lineages in individual animals within a couple weeks of infection (i.e., prior to any immune selection). This heterogeneity in lineage sizes early after infection (up...
Determination of virus sequences from individual virions enables detailed studies of intra-host dynamics, evolution, and transmission. We previously introduced high-throughput single-genome sequencing (HT-SGS) as a method that alleviates throughput-related limits faced by traditional single-genome sequencing approaches. By incorporating molecular barcodes during reverse transcription (RT) of...
Australia’s successful, rapid roll-out of PrEP from 2016 was followed by steep declines in new HIV diagnoses. Routinely reported surveillance data shows that declines are uneven across the population, with a greater decline observed in inner-Sydney. We estimated transmission clusters using protease and reverse transcriptase sequences from newly diagnosed individuals in New South Wales,...
The circulating recombinant form CRF01_AE accounts for most HIV-1 infections in South-East Asia. Here we characterized CRF01_AE’s population dynamics, including its introduction, in Thailand.
HIV-1 sequences sampled from people living with HIV-1 CRF01_AE in Thailand were downloaded from the LANL HIV database and combined with new sequences we derived from different Thai cohorts....
SARS-CoV-2 evolution is shaped by human adaptive immunity, with mutations that allow escape from the B-cell response conferring selective advantage and spreading in the population. Meanwhile, the role of the escape from T-cellular cytotoxic response remains controversial. Here, we study the origin and spread of SARS-CoV-2 variants that allow escape from presentation by the HLA class I alleles...
The early 21st century has witnessed the emergence of two coronaviral epidemics, SARS-CoV-1 (2003), MERS-CoV (2012), and a global pandemic caused by SARS-CoV-2 (2019). Despite the notable efficacy of vaccines, their imperfections, including waning immunity and emerging antigenic variants, underscore the need for continuous research in viral evolution and antigenic drift. Recognizing the...
Introduction: A single virus termed HIV-1 Transmitted/Founder (T/F) virus establishes productive clinical infection in 80% of heterosexual cases. The genetic signatures in the envelope glycoprotein (Env) of HIV-T/F subtypes B and C viruses are linked to transmission fitness. However, there is limited evidence on the unique genetic signatures in the Env of HIV-1 T/F subtypes A1, D and A1/D...
As SARS-CoV-2 has transitioned from a novel pandemic-causing pathogen into an established (but incorrigible) member of the seasonal respiratory virus community, its evolutionary imperative has changed from transmitting between hosts as efficiently as possible to the more subtle task of immune evasion, whereby it may persist in human populations for the foreseeable future. Consequently...
Ebola virus disease is a complex zoonosis that is highly virulent in humans. Despite its sorely pathogenic and lethal nature, survivors of this infection and even asymptomatic cases are able to develop both humoral and cellular immunity against several Ebola virus (EBOV) proteins. We aimed at determining immunoglobulin G (IgG) antibodies level against two Ebola viral antigens (glycoprotein and...
Introduction: An effective hepatitis C virus (HCV) vaccine must induce broadly neutralising antibodies (bnAbs) to provide protection against its high diversity. Unfortunately, there has yet to be a successful HCV vaccine that is capable of inducing bnAbs across multiple recipients. A more comprehensive understanding of the impact of viral factors, such as the properties of the infecting HCV...
Fast evaluation of vaccine effectiveness (VE) is valuable for facilitating vaccine development and making vaccination strategies. In previous studies, we developed the computational model linking molecular variations and VE for influenza and COVID-19, through which VE prediction before mass vaccination and infection is possible. In this study, we perform a complete survey of the predictive...
When the time of an HIV transmission event is unknown, methods to identify it from virus genetic data can reveal the circumstances that enable transmission. We developed a single-parameter Markov model to infer transmission time from an HIV phylogeny constructed of multiple virus sequences from people in a transmission pair. Our method finds the statistical support for transmission occurring...
Despite the success of antiretroviral therapy (ART), HIV-1 remains incurable. Most people living with HIV (PLWH) continue treatment for the rest of their lives to prevent rapid viral rebound and HIV-related disease. Understanding the host immune dynamics in response to recrudescing virus is critical to HIV cure efforts, however, the early immune response to viral rebound remains understudied....
All viruses must solve the problem of ensuring their genetic material is recognised and packaged by a viral capsid. This problem is especially intricate in viruses with segmented genomes, such as influenza viruses. Interchangeability of packaging signals in different influenza A subtypes remains a key unanswered question in determining strains' pandemic potential. The packaging signals'...
The COVID-19 pandemic has seen an order of magnitude increase in numbers of pathogen genomes sequenced. The increased availability of genomes also raised the importance of genomic data in public health policy decisions. One key use is in phylodynamic inferences, which allows estimating epidemiologically relevant parameters, such as the effective reproduction number, directly from genomic data....
Following the Zika virus (ZIKV) epidemic in the Americas, 1,089 travel-related ZIKV cases occurred in Florida between 2016-2017, together with 276 locally acquired cases in 2016. We used epidemiological data collected in Florida during 2015-2017 to develop new models to infer temporality of importation and local transmission.
We sequenced 25 ZIKV genomes from locally acquired and 38...
Geographical spread and spillover events of avian influenza viruses (AIVs) are increasing in recent times. Characterizing the intra-host variation of AIVs is crucial for understanding their evolution. However, existing sequencing methods fall short in detecting rare intra-host sequence variants and reconstructing lengthy genome regions at the single-molecule level. To address this limitation,...
Intra-host molecular evolution of HIV-1 genome sequences is thought to be critical for ensuring HIV-1 persistence during chronic, untreated infection. We have previously employed a high-throughput, single-genome amplification and sequencing (HT-SGS) approach for studies of intra-host virus diversity and evolution using unique molecular identifiers (UMIs) and the Pacific Biosciences long-read...
The Human immunodeficiency virus type I (HIV-1) is characterised by its exceptionally high genetic variability, a trait that challenges the effectiveness of therapeutic interventions and vaccine development. Therefore, a better understanding of the evolutionary dynamics of the virus remains crucial. While existing research has predominantly focused on substitutions, the exploration of...
Intra-host HIV populations overwhelmingly evolved resistance to broadly neutralizing antibodies (bNAbs) given as monotherapies in clinical trials, often doing so via multiple distinct amino acid substitutions that spread in concert. Quantifying the number of origins of bNAbs resistance within individuals is crucial for predicting how many simultaneous bNAbs must be applied to effectively...
With dozens or hundreds of minor variants of SARS-CoV-2 circulating in the global population, there is an urgent need for predicting the future frequencies of a new variant when it emerged in the population. This would allow for more focused experimental efforts and for timely formulation of new vaccines. To address this need, we constructed machine learning models, based on the transformer...
Objectives: Progressive multifocal leukoencephalopathy (PML) is an often-fatal demyelinating disease of the central nervous system, due to reactivation of JC virus (JCV) in the context of severe immune dysfunction. Pathophysiology of JCV infection is complex, and many open questions remain regarding how the virus accumulates genomic rearrangements to reactivate and specifically infects glia....
Host cells carrying integrated HIV-1 DNA (provirus) can enter a transcriptionally inactive state. The population of these cells with intact provirus comprise the latent viral reservoir (LVR). Empirically, over 90\% of proviruses in a given host are defective, \textit{i.e.}, unable to produce infectious progeny virions. In addition to large mutations introduced during reverse transcription...
A fundamental question of any program focused on the testing and timely diagnosis of a communicable disease is its effectiveness in reducing transmission. The effectiveness of these programs depends not only on which test you use, but also how you use it. Here, we introduce testing effectiveness, TE—the fraction by which testing and post-diagnosis isolation reduce transmission at the...
Understanding the within-host SARS-CoV-2 dynamics is of considerable importance for predicting clinical and public health outcomes. So far, mathematical models have been used to describe the within-host SARS-CoV-2 infection dynamics and to quantify viral load data of single individuals. Their focus has been on describing the within-host SARS-CoV-2 dynamics during the acute infection phase...
Since the onset of the pandemic, many SARS-CoV-2 variants have emerged, exhibiting substantial evolution in the virus' spike protein, the main target of neutralizing antibodies. A plausible hypothesis proposes that the virus evolves to evade antibody-mediated neutralization to maximize its ability to infect an immunologically experienced population. While virus infection induces neutralizing...
The ongoing evolution of SARS-CoV-2, marked by the continued emergence of highly divergent variants with increased transmissibility and immune evasion, underscores the importance of understanding viral evolutionary dynamics, particularly in relation to understanding the evolutionary processes involved in the emergence of these variants. We previously developed a method to identify persistent...
Australia is aiming to end the transmission of Human Immunodeficiency Virus (HIV) and Hepatitis C Virus (HCV) by 2030. National strategies for both viruses highlight the importance of timely high-quality data to improve public health responses. Such data could be obtained through a nationwide molecular epidemiology surveillance system based on routine long-range viral sequencing. However, for...
White-tailed deer (WTD) are highly susceptible to SARS-CoV-2. Multiple spillover events have been reported and studies have suggested various types of transmission (human-deer, human-deer-human, human-deer-deer)(Naderi et al., 2023)(Pickering et al., 2022). Highly dynamic polymorphisms of SARS-CoV-2 have been observed during chronic or long-term infections (Lythgoe et al, 2021). This may be...
Contrary to the global trend, between 2010 and 2022, an increase of 49% new HIV infections was recorded in Eastern Europe and Central Asia. Analyses of phylogenetic relationship, and routes and modes of transmission of the HIV-1 subtype B across the former Soviet Union (FSU) region are currently lacking. The objective of this analysis was to investigate the origin and transmission routes of...
The Antibody Mediated Prevention (AMP) trials tested the prevention efficacy of the broadly neutralizing antibody VRC01 against HIV-1 acquisition among at-risk men and transgender persons in the Americas and Europe (HVTN 704/HPTN 085) and at-risk women in sub-Saharan Africa (HVTN 703/HPTN 081). To analyze the diversity of circulating HIV-1 strains in the two trials, we conducted a phylogenetic...
Background: Hypermutated proviruses, which arise in a single replication cycle when host antiviral APOBEC proteins introduce G-to-A mutations throughout the HIV genome, persist during ART. But, their within-host origins and longevity are poorly understood because standard phylogenetic analyses, which assume that mutations arise over many replication cycles, cannot accommodate them. We describe...
Bats have become a focal point in the study of viral dynamics given their role as animal reservoirs for viruses from key families such as Coronaviridae and Paramoxyviridae. In this study, we analyzed RNA-positive samples from bat specimens collected during expeditions to countries in Asia, using primers designed to amplify the RNA-dependent RNA polymerase (RdRp) gene of known and novel...
New York City (NYC) experienced North America's largest mpox epidemic in 2022, peaking in July amid vaccine rollout. Sexually transmitted infections tend to spread across scale-free sexual networks, but it is currently unknown whether monkeypox virus (MPXV) transmission lineages recapitulate a similar network pattern. We performed phylogeographic analysis of 765 MPXV genomes from NYC sequenced...
The introduction of the hepatitis A virus (HAV) vaccine in nine Latin American countries has impacted HAV epidemiology, requiring continuous monitoring of viral strains. This study aimed to molecularly characterize and evolutionarily analyze Argentine HAV-IA strains.
From 2016 to 2023, 78 and 109 RNA-HAV+ clinical and wastewater samples, respectively, were analyzed by RT-Nested PCR targeting...
Since October 2021, the Ontario wastewater surveillance initiative has used next-generation sequencing to monitor the composition of SARS-CoV-2 RNA in wastewater samples. The fragmented nature of these data precludes using comparative methods that require full-length genomes. We developed a method to map each sample as a partial vector of mutation frequencies to a kernel space to quantify...
Viral resistance to the efficacy of antiretroviral therapy (ART) has the potential to lead to a resurgence in HIV incidence and death among people living with HIV (PLHIV). To date, there have been no longitudinal, population-based studies of HIV drug resistance trends during ART program expansion in sub-Saharan Africa. We analyzed epidemiological and virological data collected from 93,659...
Viral fitness, the ability of a virus to spread in a host population, is measured by its effective reproduction number (Re). Understanding how a virus's genotype influences its fitness can lead to the early identification of highly transmissible variants and aid in predicting viral evolution. In this study, we developed a model that predicts the Re of SARS-CoV-2 variants from their spike...
For the past decade, incidence of HIV has been on the rise in Eastern Europe and Central Asia, including the former Soviet Union (FSU) countries. Ineffective antiretroviral treatment (ART) administration leads to emergence of drug resistance mutations (DRM) leading to increased viral load. Since people living with HIV (PLWH) with higher viral load are more likely to transmit the infection, it...
Hemagglutinin (HA) and neuraminidase (NA) proteins are the primary antigenic targets of influenza A virus (IAV) infections. IAV infections are generally classified into subtypes of HA and NA proteins, e.g., H3N2. Most of the known subtypes were originally defined by a lack of antibody cross-reactivity with pre-existing subtypes. However, genome sequencing has played an increasingly important...
With the need to assess the potential impact that rapidly emerging variants will have on the population, I have worked with academic and public health (PH) teams in Canada to create and operationalize a set of tools needed for real-time evaluation and explanation of risk to senior officials and to maintain awareness across the country. In this talk, I will discuss key observations from recent...
Genetic recombination processes are a crucial driver of viral evolution and allow viruses to make large jumps in fitness space or to recombine parts of the genome with epistatic interactions. Different modes of recombination exist in RNA viruses, such as influenza or coronaviruses.
Reassortment reshuffles the spatially separated genome segments of influenza viruses and is at the heart of the...
Respiratory Syncytial Virus (RSV) is a leading cause of respiratory infections in children. As a range of novel pharmaceutical interventions for RSV being are introduced this year, it is more important than ever to have a robust understanding of the genetic diversity of RSV.
To facilitate this, we have developed a novel RSV sequencing approach and analysis pipeline for Illumina and Nanopore...
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been widespread since 2020 and will likely continue to cause significant recurring epidemics. However, understanding the underlying infection burden (i.e., including undetected asymptomatic/mild infections) and dynamics, particularly since late 2021 when the Omicron variant emerged, is challenging due to the nature of...
COVID-19 vaccine breakthrough infections have been important for all circulating SARS-CoV-2 variant periods, but the contribution of vaccine specific SARS-CoV-2 viral diversification to vaccine failure remains unclear.
This study analyzed US Military Health System beneficiaries with SARS-CoV-2 infection and who enrolled in ten Military Treatment Facilities between December 2020 and April...
Though viral load is suppressed, a latent reservoir of HIV persists during antiretroviral therapy (ART), meaning people living with HIV (PWH) must take ART indefinitely. We have hypothesized that persistence is driven predominantly by natural processes of CD4+ T cells harboring integrated HIV DNA proviruses. Here we measure and compare the clonality and clonal dynamics of HIV proviruses to...
Warming climate and extreme weather events are changing the range of virus-competent mosquito species and their animal hosts, bringing viruses in contact with immunologically naive human populations. In Australia, this has resulted in unusual epidemics, including the 2022 emergence of Japanese Encephalitis Virus (JEV), and a spike in cases of Murray Valley Encephalitis Virus in 2023. Australia...
Controversy continues to surround the evolutionary origins of SARS-CoV-2, particularly in light of the absence of an identified intermediate host. A prior outbreak of severe acute respiratory syndrome caused by SARS-CoV was traced back to palm civets from a live-animal market and farms in Guangdong Province, China. While the direct observation of zoonotic events between bats and humans via an...
Dengue virus (DENV) is a significant public health concern in Colombia. Since a large outbreak in 2019, the departments of Risaralda and Valle del Cauca have experienced increased incidence of arboviral disease. Phylogeographic tools are critical to understanding DENV diversity, persistence, and spread across Colombia. Therefore, this study analyzed plasma samples from individuals with...
In 2021, the Joint United Nations Programme on HIV and AIDS (UNAIDS) upgraded their original 90-90-90 targets set in 2014 to 95-95-95. These targets state that by 2025: (1) 95% of all people living with HIV (PLHIV) should be diagnosed; (2) 95% of all diagnosed PLHIV should be on antiretroviral therapy (ART); and (3) 95% of those on ART should be virally suppressed. While calculating the latter...
Background: By using genomic sequences, molecular epidemiology has the potential to reconstruct HIV transmission networks, provide insights into disease transmission dynamics, and inform public health strategies. It is believed that long sequences, such as near full-length HIV genome sequences, can improve the accuracy of phylogenetic inference. However, relatively short pol sequences are...
A poorly understood phenomenon of the COVID-19 pandemic has been the regular switching between major variants that have the 69-70 deletion in Spike, which leads to dropout of the S gene during RT-PCR testing, and those that do not. However, the biological underpinnings for this switching are poorly understood.
We hypothesised that variants that share the same S-gene target failure (SGTF)...
Approximately 90% of clinical diagnoses of influenza-like illness are not caused by influenza viruses (United States CDC), but rather by other respiratory pathogens, including respiratory syncytial virus (RSV). In temperate regions, including the United States, RSV demonstrates seasonality, with cases peaking in the colder months and approaching zero in the warmer months (Moriyama et al. 2020;...
Background: Previous work from our group identified a tight bottleneck for influenza A virus (IAV) that restricts the transmission of genetic diversity. The impact of viral (subtype and strain) and host (age, vaccination status) factors on bottleneck size are unclear. The 2021/2022 H3N2 season was characterized by strains that were antigenically drifted and exhibited a high household secondary...
Using the NIH ACTIV-TRACE initiative, we have an automated database of mutations of all publicly deposited SARS-CoV-2 raw sequences on NCBI’s short read archive (SRA). Our project delved into exploring the minor variants, those that occupy each position at a minority frequency per sample, in the VCF files that catalog each sample’s mutations. While minority variants are considered a proxy of...
Reductions in HIV infection rates in sub-Saharan Africa (SSA) do not fully reflect the increases in viral load suppression achieved through universal testing and treatment (UTT). Heterogeneities in risk and treatment uptake contribute to this disparity. In North America and Europe, HIV transmission is concentrated among key populations with frequent super spreading. The extent to which African...
Molecular epidemiology and evolutionary genetic methods can provide critical insights into public health program performance and quantitatively direct programmatic enhancements. The United Nations (UN) targets: 95-95-95 by 2025 Targets, aim to decrease AIDS deaths and HIV new infections by at least 90% by 2030, meeting the UN-defined “End of HIV/AIDS as a pandemic concern”. Herein, we develop...
Introduction
Ongoing HIV transmission is a formidable public health challenge in Indonesia, where prevalence is 0.3% and persons with HIV (PWH) are distributed across >6,000 inhabited islands over 5,000 km. Incidence is likely substantial; we estimated c.10% of newly diagnosed PWH were recent infections (Wulan et al., 2023). To identify factors responsible for contemporary HIV spread, we...
By the end of 2020, a nationwide SARS-CoV-2 genomic surveillance consortium was established in Belgium. During this period, emphasis was placed on the real-time analysis of circulating variants and case studies. Moving away from real-time analyses, our focus now shifts towards exploiting the resulting comprehensive set of SARS-CoV-2 sequences to perform a retrospective analysis on the...
Background: G1P[8] rotaviruses consistently circulated in Malawi from 1997 to 2019. They represent genogroup I and normally possess a Wa-like genetic backbone. However, the majority of G1P[8] strains that circulated between 2013 and 2014 in Blantyre, Malawi soon after the introduction of Rotarix® rotavirus vaccine, exhibited a DS-1-like genetic backbone more common of genogroup II...
The process of reassortment plays a crucial role in driving the transmission dynamics of influenza viruses across species barriers. Since 2020, the H5 Highly Pathogenic Avian Influenza (HPAIV) panzootic has caused significant outbreaks in poultry, wild birds and marine mammals. Extensive reassortment of the virus's eight gene segments have occurred across populations, disseminating extensive...
The evolution of SARS-Coronavirus-2 (SARS-CoV-2) has been characterized by the periodic emergence of highly divergent variants. One leading hypothesis suggests these variants may have emerged during chronic infections of immunocompromised individuals, but limited data from these cases hinders comprehensive analyses. Here, we harnessed millions of SARS-CoV-2 genomes to identify potential...
A high proportion of SARS-CoV-2 transmissions happen within households, making accurate identification of sources and recipients of infection within households important for designing effective public health strategies. However, traditional epidemiological data can rarely confirm transmission paths and directions. We used the UK’s Office for National Statistics COVID-19 Infection Survey (CIS)...
Background:
The WHO first-line HIV-1 treatment regimen changed to include dolutegravir in 2019 in response to increasing drug resistance. Drug resistance while on dolutegravir-containing therapy is rare, but has been observed even in previously untreated individuals. Previous work has analysed patterns of resistance in clinical data and postulated that for some drug combinations,...
Since the coining of the tern phylodynamics the use of phylogenies to learn epidemiological information has steadily increased. As methods have proliferated and grown more computationally expensive the epidemiological information they extract has also evolved to better compliment what can be learned through traditional epidemiological data. However, for genomic epidemiology to continue to...
Historically epidemiological contact-tracing data has often reported much higher rates of transmission between household contacts compared to non-household contacts. SARS-CoV-2 has a proof-reading mechanism resulting in a relatively slow mutation rate (e.g. compared to influenza). In high transmission periods we expect true transmission pairs to have, at most, 1 single-nucleotide polymorphism...
Host immunity drives the evolution of many pathogens towards antigenic escape. However, the contribution towards this escape may not be uniform across the population: different types of hosts may contribute more or less in terms of both immune pressure and onward transmission. Here we investigate the population-level consequences of this heterogeneity, focussing on vaccine escape.
This...
RNA viruses exist in large heterogeneous populations within their host, impacting disease progression and treatment outcomes. To effectively control spread and develop targeted treatments and vaccines, quantitative characterization of within-host viral genetic diversity is crucial. Next-generation sequencing allows for comprehensive analysis of viral populations, from single-nucleotide...
A near-ubiquitous approach to phylogenetic reconstruction has been to model variation in nucleotide substitution rates amongst genomic sites using a discretised Gamma distribution. We have recently demonstrated that this model introduces a bias in reconstructed branch lengths, such that their magnitude is largely driven by the number of sequences in the dataset. The alternative “FreeRate”...
Using data from the LANL HIV database, we find that the prevalence of HIV-1 subtypes B, C, and BC recombinants have a remarkably sustained ratio over time in Brazil. We explore explanations for this phenomenon by building an ordinary differential equation model where two variants of HIV-1 are introduced into a population (not necessarily at the same time), and where the two variants can...
