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Biomedical subjects

Edward C Holmes

Publications and source records attributed to Edward C Holmes.

8 recordsLinked to original sources

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

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

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

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

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

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

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

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