Biology subjects

Gatherer, D.

Publications and source records attributed to Gatherer, D..

4 recordsLinked to original sources

bioRxiv2022

Genomic Analysis of Two Phlebotomine Sand Fly Vectors of Leishmania from the New and Old World

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the devastating kinetoplastid parasites of the genus Leishmania, the causative agents of diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. As no approved efficacious vaccine exists, available drugs are expensive and/or toxic, and resistance is emerging, management of sand fly populations to break transmission is currently the most effective disease control strategy. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two of the most important sand fly species: Phlebotomus papatasi, a cutaneous leishmaniasis vector, (distributed in the Middle East and North Africa) and Lutzomyia longipalpis, a visceral leishmaniasis vector (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites. Author SummaryThe leishmaniases are a group of neglected tropical diseases caused by protist parasites from the Genus Leishmania. Different Leishmania species present a wide clinical profile, ranging from mild, often self-resolving cutaneous lesions that can lead to protective immunity, to severe metastatic mucosal disease, to visceral disease that is ultimately fatal. Leishmania parasites are transmitted by the bites of sand flies, and as no approved vaccine exists, available drugs are toxic and/or expensive and resistance is emerging, new dual control strategies to combat these diseases must be developed, combining interventions on human infections and integrated sand fly population management. Effective vector control requires a good understanding of the biology of sand flies. To this end, we sequenced and annotated the genomes of two sand fly species that are important leishmaniasis vectors from the Old and New Worlds. These genomes allow us to better understand, at the genetic level, processes important in the vector biology of these species, such as finding hosts, blood-feeding, immunity, and detoxification. These genomic resources highlight the driving forces of evolution of two major Leishmania vectors and provide foundations for future research on how to better prevent leishmaniasis by control of the sand fly vectors.

genomics↗

bioRxiv2020

Immunological cross-reactions with paramyxovirus nucleoproteins may explain sporadic apparent ebolavirus seropositivity in European populations.

Although confirmed outbreaks of Ebola Virus Disease (EVD) have been confined to central and west Africa, seropositivity to Zaire ebolavirus (EBOV) has been reported in other parts of Africa and even in one study from the early 1990s in Germany. The possible reasons for the discrepancy between serological studies and clinical evidence, remain uncertain. Here, we report anonymous serum donors sampled in Lancaster (UK) with seropositivity by ELISA to EBOV nucleoprotein at a frequency of approximately 2%. In one serum donor, we confirm the result using Western blot. This is only the second report of seropositivity for EBOV outside of Africa. Our samples are negative to EBOV glycoprotein, suggesting that the seropositivity is specific to the nucleoprotein and may be due to cross-reaction with antibodies produced by exposure to another virus. To investigate potential candidates for this cross-reacting virus, we perform bioinformatics analysis that suggests that EBOV nucleoprotein has structural similarity to paramyxovirus nucleoproteins at a candidate immunological epitope. Cross-reaction of antibodies against paramyxovirus nucleoproteins, with EBOV nucleoprotein antigens used in serological testing, may be the cause of the rare instances of ebolavirus seropositivity in Europe, and may also be a confounding factor in African serosurveys.

microbiology↗

bioRxiv2018

Phylodynamic analysis of the historical spread of Toscana virus around the Mediterranean

All available sequences of the three genome segments of Toscana virus with date and location of sampling were analysed using Bayesian phylodynamic methods. We estimate that extant Toscana virus strains had a common ancestor in the late 16th to early 17th century AD, in territories controlled by the Ottoman Empire, giving rise to an ancestral genotype A/B in north Africa and to genotype C in the Balkans. Subsequent spread into western Europe may have occurred during the period of European colonization of north Africa in the 19th and early 20th centuries AD, establishing genotypes A and B in Italy and Spain respectively. Very little positive evolutionary selection pressure is detectable in Toscana virus, suggesting that the virus has become well adapted to its human hosts. There is also no convincing evidence of reassortment between genome segments, despite genotypes A and B now co-circulating in several countries.

microbiology↗

bioRxiv2016

Influenza C incidence and herd immunity in Lancaster, UK, in the winter of 2014-2015

Influenza C is not included in the annual seasonal influenza vaccine, and has historically been regarded as a minor respiratory pathogen. However, recent work has highlighted its potential role as a cause of pneumonia in infants. We performed nasopharyngeal or nasal swabbing and/or serum sampling (n=148) in Lancaster, UK, over the winter of 2014-2015. Using enzyme-linked immunosorbent assay (ELISA), we estimated a seropositivity of 77%. By contrast, only 2 individuals, both asymptomatic adults, were influenza C-positive by polymerase chain reaction (PCR). Deep sequencing of nasopharyngeal samples produced partial sequences for 4 genome segments in one of these patients. Bayesian phylogenetic analysis demonstrated that the influenza C genome from this individual is evolutionarily distant to those sampled in recent years and represents a novel genome constellation, indicating that it is a product of a decades-old reassortment event. Although we find no evidence that influenza C was a significant respiratory pathogen during the winter of 2014-2015 in Lancaster, we confirm previous observations of seropositivity in the majority of the population. We calculate that this level of herd immunity would be sufficient to suppress epidemics of influenza C and restricts the virus to sporadic endemic spread.

microbiology↗