Biomedical subjects

Edward C Holmes

Publications and source records attributed to Edward C Holmes.

At least 19 recordsLinked to original sources

PubMed2026

Genomic epidemiology of coxsackievirus A24 variant during the 2024 acute hemorrhagic conjunctivitis outbreak in Coastal Kenya.

Several African countries experienced a surge in acute hemorrhagic conjunctivitis (AHC) cases in 2024. Investigations in Kenya, Mayotte (an Indian Ocean island) and Tanzania identified coxsackievirus A24 variant (CVA24v) as the causative agent. To date, however, limited genomic data exist to elucidate the sources, epidemiology, and evolution of CVA24v in Africa. We generated 245 CVA24v genomes from samples collected between January and September 2024 in coastal Kenya, representing the largest outbreak CVA24v genomic data set available globally. Phylogenetic analysis showed that these viruses belonged to genotype IV, falling into two major clusters that differed by 52 nucleotide and five amino acid changes, and with an inter-species recombination event involving another enterovirus in the 3Dpol gene. Notably, the Kenyan sequences clustered closely with contemporaneous Africa (2024) sequences, specifically Mayotte and Malawi, reflecting a regionally connected CVA24v outbreak, but were distinct from those sampled previously in Asia in 2023, with phylodynamic analysis revealing that the Most Recent Common Ancestor of Kenyan sequences existed between June and October 2023. In summary, this study provides the first detailed genomic analysis of CVA24v from Africa to inform future surveillance and control strategies.

Journal Article↗

PubMed2026

Viral community structure in New Zealand's aquatic birds is associated with scavenging behavior.

Wild migratory birds play a major role in the global spread of viruses, yet the ecological drivers underpinning viral diversity and transmission, particularly host behavior, remain poorly understood. Aotearoa/New Zealand provides a powerful system to address this, including unique species that reflect its geographical isolation, yet with international connections provided by migratory birds across the East Asian-Australasian Flyway and Antarctic regions. Herein, we conducted a large-scale metatranscriptomic survey of wild birds across New Zealand and its subantarctic islands, in which we collected 1,348 samples from 690 individuals across 31 host species spanning four avian orders. We identified 118 avian viruses from 17 families, including 107 novel species, expanding our knowledge of avian viral diversity. Notably, viral community composition was most strongly associated with bird scavenging behavior, which explained more variation than host taxonomy, geography, or migratory status. Scavenging birds and opportunistic scavengers harbored more diverse viromes than non-scavengers, consistent with increased viral exposure across trophic levels. This was supported by the detection of 12 mammalian-associated viruses, primarily in scavengers, including hedgehog hepatovirus, rabbit hemorrhagic disease virus 2, and sea lion astroviruses, with host sequence data confirming dietary origin. We also detected viruses of epidemiological and evolutionary interest, including a low-pathogenic avian influenza A(H1N9) virus from red knots (Calidris canutus) and a divergent tobanivirus from Auckland Island teal (Anas aucklandica), which represented the first putative avian member of the Tobaniviridae. These findings suggest that virome structure in wild birds is associated with scavenging behavior, thus highlighting the importance of incorporating host ecology into viral surveillance and risk assessment.

New Zealand↗

PubMed2026

Genomic and evolutionary basis of parthenogenesis in a disease-vector tick species.

Haemaphysalis longicornis is an important tick species and pathogen vector characterized by the co-circulation of triploid parthenogenetic and diploid bisexual strains. However, the evolutionary basis of parthenogenesis in this species is unclear. Here we report reference-quality, haplotype-resolved genome assemblies of the parthenogenetic strain and two reference-quality genomes of the bisexual strains. Comparative genomic analysis revealed high collinearity between the parthenogenetic and bisexual genomes, with a stable chromosomal architecture maintained among the three haplotypes of the parthenogenetic strain. The parthenogenetic H. longicornis genome exhibited a major expansion in cell cycle-related gene families, including the inhibitor of apoptosis protein (IAP) family, but was characterized by a contraction in other gene families. Population resequencing of 179 individuals revealed two distinct subpopulations, with chromosome 7 harbouring high genetic differentiation and several candidate genes probably associated with parthenogenesis. Functional experiments showed that knockdown of the BIRC5 gene, a member of the IAP family, suppressed oviposition in both strains, with the parthenogenetic strain exhibiting milder adverse effects probably due to a stronger transcriptional response. Overall, our results reveal the genomic and evolutionary features associated with polyploid parthenogenesis in H. longicornis.

Animals↗

PubMed2026

Hidden diversity of coronaviruses in high-altitude plateau mammals.

• Pikas and marmots from plateaus host divergent α- and β-CoVs, including the candidate subgenera Pibecovirus and Mabecovirus. • The plateau CoVs show distinctive genomic features (relocated HE gene, variable ORFs), indicating lineage-specific evolution. • High-altitude plateau ecosystems are a key yet understudied frontier of CoV evolution, warranting systematic surveillance.

Journal Article↗

PubMed2025

Coxsackievirus A24 variant whole genome sequencing from clinical samples using a three overlapping amplicons strategy.

In January 2024, the Kenya Ministry of Health issued an outbreak alert following a surge in acute hemorrhagic conjunctivitis (AHC) cases along the Kenyan coast. Our investigations identified coxsackievirus A24 variant (CV-A24v) as the causative agent. In this study, we developed a novel whole genome sequencing assay for CV-A24v, and used it to recover three near complete genomes from the 2024 AHC outbreak in Kenya. This method will support future studies on CV-A24v genomic epidemiology and evolution across Kenya and beyond.

Acute Hemorrhagic Conjunctivitis Kenya↗

PubMed2025

Genomic and clinical epidemiology of SARS-CoV-2 in coastal Kenya: insights into variant circulation, reinfection, and multiple lineage importations during a post-pandemic wave.

BACKGROUND: Between November 2023 and March 2024, coastal Kenya experienced another wave of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections detected through our continued genomic surveillance. Herein, we report the clinical and genomic epidemiology of SARS-CoV-2 infections from 179 individuals (a total of 185 positive samples) residing in the Kilifi Health and Demographic Surveillance System (KHDSS) area (~ 900 km2). METHODS: We analyzed genetic, clinical, and epidemiological data from SARS-CoV-2 positive cases across pediatric inpatient, health facility outpatient, and homestead community surveillance platforms. Phylogenetic analyses were performed using maximum-likelihood and Bayesian frameworks. Temporal trends were summarized, comparisons conducted using Kruskal-Wallis and Wilcoxon tests, and associations examined using univariate and multivariable logistic regression models. RESULTS: Sixteen SARS-CoV-2 lineages within 3 subvariants [XBB.2.3-like (58.4%), JN.1-like (40.5%), and XBB.1-like (1.1%)] were identified. The symptomatic infection rate was estimated at 16.0% (95% CI, 11.1-23.9%) based on community testing regardless of symptom status and did not differ across the subvariants (p = 0.13). The most common infection symptoms in community cases were cough (49.2%), fever (27.0%), sore throat (7.3%), headache (6.9%), and difficulty in breathing (5.5%). One case succumbed to the infection. Genomic analysis of the virus from serial positive samples confirmed repeat infections among 5 participants under follow-up (median interval 21 days, range 16-95 days); in 4 participants, the same virus lineage was responsible in both episodes, whereas 1 participant had a different lineage in the second compared with the first episode. Phylogenetic analysis including > 18,000 contemporaneous global sequences provided evidence for at least 38 independent virus introduction events into the study area (KHDSS) during the wave, the majority likely originating in North America and Europe. CONCLUSIONS: Our study highlights that coastal Kenya, like most other localities, continues to face new SARS-CoV-2 infection waves characterized by circulation of new variants, multiple lineage importations, and reinfections. Locally, the virus may circulate unrecognized, as most infections are asymptomatic in part due to high population immunity after several waves of infection. Our findings highlight the need for sustained SARS-CoV-2 surveillance to inform appropriate public health responses, such as scheduled vaccination for populations at risk of severe infection.

COVID-19↗

PubMed2025

A positive-sense single-stranded RNA virus acquired a negative-sense open reading frame through recombination.

Although positive- and negative-sense single-stranded RNA viruses are ubiquitous in nature, there is currently no evidence of recombination or reassortment between viruses with these two major forms of genome organization. Here, we describe the discovery of brine shrimp virga-like virus 1 (BSVV1), a novel positive-sense single-stranded RNA virus with a recombinant genome structure derived from two viral phyla with differing genome organizations. The genome of BSVV1 comprises three open reading frames (ORFs). ORF1 resembles the RNA-dependent RNA polymerase of Ips virga-like virus 1 (a positive-sense RNA virus), while ORF2, transcribed in the positive orientation, is related to the glycoprotein of Hubei bunya-like virus 10 and other negative-sense RNA viruses. The predicted ORF3 was unique to BSVV1 without known homologs identified. The presence of the three protein products was verified by mass spectrometry. Notably, our analysis also revealed that BSVV1 is geographically widespread and found in brine shrimp from at least eight countries on four continents. In addition, BSVV1 was successfully cultured and proliferated to high viral loads during brine shrimp development. In sum, we provide compelling evidence of an ancient recombination event between negative- and positive-sense single-stranded RNA viruses, enriching our understanding of the evolution of genome structures in RNA viruses.

Open Reading Frames↗

PubMed2025

Making sense of the virome in light of evolution and ecology.

Understanding the patterns and drivers of viral prevalence and abundance is of key importance for understanding pathogen emergence. Over the last decade, metagenomic sequencing has exponentially expanded our knowledge of the diversity and evolution of viruses associated with all domains of life. However, as most of these 'virome' studies are primarily descriptive, our understanding of the predictors of virus prevalence, abundance and diversity, and their variation in space and time, remains limited. For example, we do not yet understand the relative importance of ecological predictors (e.g. seasonality and habitat) versus evolutionary predictors (e.g. host and virus phylogenies) in driving virus prevalence and diversity. Few studies are set up to reveal the factors that predict the virome composition of individual hosts, populations or species. In addition, most studies of virus ecology represent a snapshot of single species viromes at a single point in time and space. Fortunately, recent studies have begun to use metagenomic data to directly test hypotheses about the evolutionary and ecological factors which drive virus prevalence, sharing and diversity. By synthesizing evidence across studies, we present some over-arching ecological and evolutionary patterns in virome composition, and illustrate the need for additional work to quantify the drivers of virus prevalence and diversity.

Virome↗

PubMed2007

Phylogenetic evidence for deleterious mutation load in RNA viruses and its contribution to viral evolution.

Populations of RNA viruses are often characterized by abundant genetic variation. However, the relative fitness of these mutations is largely unknown, although this information is central to our understanding of viral emergence, immune evasion, and drug resistance. Here we develop a phylogenetic method, based on the distribution of nonsynonymous and synonymous changes, to assess the relative fitness of polymorphisms in the structural genes of 143 RNA viruses. This reveals that a substantial proportion of the amino acid variation observed in natural populations of RNA viruses comprises transient deleterious mutations that are later purged by purifying selection, potentially limiting virus adaptability. We also demonstrate, for the first time, the existence of a relationship between amino acid variability and the phylogenetic distribution of polymorphisms. From this relationship, we propose an empirical threshold for the maximum viable deleterious mutation load in RNA viruses.

Amino Acid Sequence↗

PubMed2006

Declining growth rate of West Nile virus in North America.

To determine the demographic history of West Nile virus (WNV) in North America, we employed a coalescent method to envelope coding region data sets for the NY99 and WN02 genotypes. Although the observed genetic diversities in both genotypes were of approximately the same age, the mean rate of epidemiological growth of the WN02 population was approximately three times that of the NY99 population, a finding compatible with the recent dominance of the former genotype. However, there has also been a marked decrease in the recent growth rate of WN02, suggesting that WNV has reached its peak prevalence in North America.

Animals↗

PubMed2006

Genetic characterization of tick-borne flaviviruses: new insights into evolution, pathogenetic determinants and taxonomy.

Here, we analyze the complete coding sequences of all recognized tick-borne flavivirus species, including Gadgets Gully, Royal Farm and Karshi virus, seabird-associated flaviviruses, Kadam virus and previously uncharacterized isolates of Kyasanur Forest disease virus and Omsk hemorrhagic fever virus. Significant taxonomic improvements are proposed, e.g. the identification of three major groups (mammalian, seabird and Kadam tick-borne flavivirus groups), the creation of a new species (Karshi virus) and the assignment of Tick-borne encephalitis and Louping ill viruses to a unique species (Tick-borne encephalitis virus) including four viral types (i.e. Western Tick-borne encephalitis virus, Eastern Tick-borne encephalitis virus, Turkish sheep Tick-borne encephalitis virus and Louping ill Tick-borne encephalitis virus). The analyses also suggest a complex relationship between viruses infecting birds and those infecting mammals. Ticks that feed on both categories of vertebrates may constitute the evolutionary bridge between the three distinct identified lineages.

Animals↗

PubMed2006

Long intervals of stasis punctuated by bursts of positive selection in the seasonal evolution of influenza A virus.

BACKGROUND: The interpandemic evolution of the influenza A virus hemagglutinin (HA) protein is commonly considered a paragon of rapid evolutionary change under positive selection in which amino acid replacements are fixed by virtue of their effect on antigenicity, enabling the virus to evade immune surveillance. RESULTS: We performed phylogenetic analyses of the recently obtained large and relatively unbiased samples of the HA sequences from 1995-2005 isolates of the H3N2 and H1N1 subtypes of influenza A virus. Unexpectedly, it was found that the evolution of H3N2 HA includes long intervals of generally neutral sequence evolution without apparent substantial antigenic change ("stasis" periods) that are characterized by an excess of synonymous over nonsynonymous substitutions per site, lack of association of amino acid replacements with epitope regions, and slow extinction of coexisting virus lineages. These long periods of stasis are punctuated by shorter intervals of rapid evolution under positive selection during which new dominant lineages quickly displace previously coexisting ones. The preponderance of positive selection during intervals of rapid evolution is supported by the dramatic excess of amino acid replacements in the epitope regions of HA compared to replacements in the rest of the HA molecule. In contrast, the stasis intervals showed a much more uniform distribution of replacements over the HA molecule, with a statistically significant difference in the rate of synonymous over nonsynonymous substitution in the epitope regions between the two modes of evolution. A number of parallel amino acid replacements - the same amino acid substitution occurring independently in different lineages - were also detected in H3N2 HA. These parallel mutations were, largely, associated with periods of rapid fitness change, indicating that there are major limitations on evolutionary pathways during antigenic change. The finding that stasis is the prevailing modality of H3N2 evolution suggests that antigenic changes that lead to an increase in fitness typically result from epistatic interactions between several amino acid substitutions in the HA and, perhaps, other viral proteins. The strains that become dominant due to increased fitness emerge from low frequency strains thanks to the last amino acid replacement that completes the set of replacements required to produce a significant antigenic change; no subset of substitutions results in a biologically significant antigenic change and corresponding fitness increase. In contrast to H3N2, no clear intervals of evolution under positive selection were detected for the H1N1 HA during the same time span. Thus, the ascendancy of H1N1 in some seasons is, most likely, caused by the drop in the relative fitness of the previously prevailing H3N2 lineages as the fraction of susceptible hosts decreases during the stasis intervals. CONCLUSION: We show that the common view of the evolution of influenza virus as a rapid, positive selection-driven process is, at best, incomplete. Rather, the interpandemic evolution of influenza appears to consist of extended intervals of stasis, which are characterized by neutral sequence evolution, punctuated by shorter intervals of rapid fitness increase when evolutionary change is driven by positive selection. These observations have implications for influenza surveillance and vaccine formulation; in particular, the possibility exists that parallel amino acid replacements could serve as a predictor of new dominant strains. REVIEWERS: Ron Fouchier (nominated by Andrey Rzhetsky), David Krakauer, Christopher Lee.

Journal Article↗

PubMed2006

Extremely rapid spread of human immunodeficiency virus type 1 BF recombinants in Argentina.

The epidemic of human immunodeficiency virus type 1 (HIV-1) in Argentina is distinctive in that many infections are caused by subtype BF recombinant viruses. To determine their demographic history, we estimated the evolutionary rate, mode of population growth, and age of genetic diversity among 40 BF vpu sequences. This revealed one of the highest substitution rates reported for HIV-1, at 10.793 x 10(-3) substitutions per site per year, and a very rapid rate of population growth, with an initial mean epidemic doubling time of 3.72 months. This rapid population growth is compatible with an elevated fitness for subtype BF compared to that for "pure" B and F viruses.

Argentina↗

PubMed2006

Comment on "Large-scale sequence analysis of avian influenza isolates".

Obenauer et al. (Research Articles, 17 March 2006, p. 1576) reported that the influenza A virus PB1-F2 gene is evolving under strong positive selection, as documented by an extremely high ratio of the number of nonsynonymous nucleotide substitutions to the number of synonymous substitutions (dN/dS). However, we show that this observation is likely to be an artifact related to the location of PB1-F2 in the +1 reading frame of the PB1 gene.

Animals↗

PubMed2006

Avian influenza virus exhibits rapid evolutionary dynamics.

Influenza A viruses from wild aquatic birds, their natural reservoir species, are thought to have reached a form of stasis, characterized by low rates of evolutionary change. We tested this hypothesis by estimating rates of nucleotide substitution in a diverse array of avian influenza viruses (AIV) and allowing for rate variation among lineages. The rates observed were extremely high, at >10(-3) substitutions per site, per year, with little difference among wild and domestic host species or viral subtypes and were similar to those seen in mammalian influenza A viruses. Influenza A virus therefore exhibits rapid evolutionary dynamics across its host range, consistent with a high background mutation rate and rapid replication. Using the same approach, we also estimated that the common ancestors of the hemagglutinin and neuraminidase sequences of AIV arose within the last 3,000 years, with most intrasubtype diversity emerging within the last 100 years and suggestive of a continual selective turnover.

Animals↗

PubMed2006

A phylogenetic method for detecting positive epistasis in gene sequences and its application to RNA virus evolution.

RNA virus genomes are compact, often containing multiple overlapping reading frames and functional secondary structure. Consequently, it is thought that evolutionary interactions between nucleotide sites are commonplace in the genomes of these infectious agents. However, the role of epistasis in natural populations of RNA viruses remains unclear. To investigate the pervasiveness of epistasis in RNA viruses, we used a parsimony-based computational method to identify pairs of co-occurring mutations along phylogenies of 177 RNA virus genes. This analysis revealed widespread evidence for positive epistatic interactions at both synonymous and nonsynonymous nucleotide sites and in both clonal and recombining viruses, with the majority of these interactions spanning very short sequence regions. These findings have important implications for understanding the key aspects of RNA virus evolution, including the dynamics of adaptation. Additionally, many comparative analyses that utilize the phylogenetic relationships among gene sequences assume that mutations represent independent, uncorrelated events. Our results show that this assumption may often be invalid.

DNA Mutational Analysis↗

PubMed2006

Host species barriers to influenza virus infections.

Most emerging infectious diseases in humans originate from animal reservoirs; to contain and eradicate these diseases we need to understand how and why some pathogens become capable of crossing host species barriers. Influenza virus illustrates the interaction of factors that limit the transmission and subsequent establishment of an infection in a novel host species. Influenza species barriers can be categorized into virus-host interactions occurring within individuals and host-host interactions, either within or between species, that affect transmission between individuals. Viral evolution can help surmount species barriers, principally by affecting virus-host interactions; however, evolving the capability for sustained transmission in a new host species represents a major adaptive challenge because the number of mutations required is often large.

Animals↗

PubMed2006

The evolutionary history and dynamics of bat rabies virus.

Rabies virus (RABV) is endemic in terrestrial mammals throughout the world and in bats on the American continent. We performed the most extensive phylogenetic analyses of bat RABV sequences undertaken to date using a variety of genes. Our study supported previous suggestions that viral sequences are grouped according to the behaviour of the host species. However, there was more genetic and geographical diversity within each phylogenetic group than previously recognised, including evidence for new groups. Furthermore, three clades of Latin American bat RABV that were distinct from the previously identified "group IV" bat RABV clade and more closely related to North American bat RABV clades, were identified. Strikingly, phylogenetic trees for the G (glycoprotein) gene had a significantly different evolutionary history to those inferred for the N (nucleoprotein) and P (phosphoprotein) genes, and an analysis of these competing topologies revealed that it is not possible on current data to resolve whether bat RABV arose from terrestrial mammal RABV, or vice-versa. Finally, using coalescent approaches, we estimated that RABV had similar rates of population growth and nucleotide substitution (approximately 2.5-4x10(-4) substitutions per site, per year) in both bats and terrestrial mammals, despite underlying differences in epidemiology.

Animals↗