Biology subjects

English, S.

Publications and source records attributed to English, S..

3 recordsLinked to original sources

bioRxiv2022

Structure of trimeric pre-fusion rabies virus glycoprotein in complex with two protective antibodies

Rabies virus (RABV) causes lethal encephalitis and is responsible for approximately 60,000 deaths per year. As the sole virion-surface protein, the rabies virus glycoprotein (RABV-G) mediates host-cell entry. RABV-Gs pre-fusion trimeric conformation displays epitopes bound by protective neutralizing antibodies which can be induced by vaccination or passively administered for post-exposure prophylaxis. We report a 2.8-[A] structure of a RABV-G trimer in the pre-fusion conformation, in complex with two neutralizing and protective monoclonal antibodies, 17C7 and 1112-1. One of these antibodies is a licensed prophylactic (17C7, Rabishield), which we show locks the protein in pre-fusion conformation. We demonstrate that targeted mutations can stabilize RABV-G in the pre-fusion conformation, a key step towards structure-guided vaccine design. These data reveal the higher-order architecture of a key therapeutic target and the structural basis of neutralization by antibodies binding two key antigenic sites, and will facilitate the development of improved vaccines and prophylactic antibodies.

microbiology↗

bioRxiv2022

Live-bearing cockroach genome reveals convergent evolutionary mechanisms linked to viviparity in insects and beyond

Insects provide an unparalleled opportunity to link genomic changes with the rise of novel phenotypes, given tremendous variation in the numerous and complex adaptations displayed across the group. Among these numerous and complex adaptations, live-birth has arisen repeatedly and independently in insects and across the tree of life, suggesting this is one of the most common types of convergent evolution among animals. We sequenced the genome and transcriptome of the Pacific beetle-mimic cockroach, the only truly viviparous cockroach, and performed comparative analyses including two other viviparous insect lineages, the tsetse and aphids, to unravel the genomic basis underlying the transition to viviparity in insects. We identified pathways experiencing adaptive evolution, common in all viviparous insects surveyed, involved in uro-genital remodeling, maternal control of embryo development, tracheal system, and heart development. Our findings suggest the essential role of those pathways for the development of placenta-like structure enabling embryo development and nutrition. Viviparous transition seems also to be accompanied by the duplication of genes involved in eggshell formation. Our findings from the viviparous cockroach and tsetse reveal that genes involved in uterine remodeling are up-regulated and immune genes are down-regulated during the course of pregnancy. These changes may facilitate structural changes to accommodate developing young and protect them from the mothers immune system. Our results denote a convergent evolution of live-bearing in insects and suggest similar adaptive mechanisms occurred in vertebrates, targeting pathways involved in eggshell formation, uro-genital remodeling, enhanced tracheal and heart development, and reduced immunity.

genomics↗

bioRxiv2021

Differential transcriptomic response of Anopheles arabiensis to Plasmodium vivax and Plasmodium falciparum infection

Plasmodium vivax malaria is now recognized as the second most dangerous parasitic threat to human health with the regular decrease of Plasmodium falciparum worldwide over recent decades. A very limited numbers of studies address the interaction of P. vivax with its Anopheles mosquito vectors. Those studies were conducted in P. vivax endemic countries with P.vivax local major vectors for which limited genomic and genetic tools are available. Despite the presence of P. vivax in several African countries and increasing reports on its occurrence in many others, there is virtually no data on the molecular responses of Anopheles arabiensis, a major African mosquito vector, to P. vivax, which limits the development of further "mosquito-targeted" interventions aimed at reducing P. vivax transmission. Taking advantage of the situation of Madagascar where P. falciparum, P. vivax and An. arabiensis are present, we explore the molecular responses of An. arabiensis towards these two human malaria parasites. RNA sequencing on RNAs isolated from mosquito midguts dissected at the early stage of infection (24 hours) was performed using mosquitoes fed on the blood of P. vivax and P. falciparum gametocyte carriers in a field station. From a de novo assembly of An. arabiensis midgut total RNA transcriptome, the comparative analysis revealed that a greater number of genes were differentially expressed in the mosquito midgut in response to P. vivax (209) than to P. falciparum (81). Among these, 15 common genes were identified to be significantly expressed in mosquito midgut 24 hours after ingesting P. vivax and P. falciparum gametocytes, including immune responsive genes and genes involved in amino-acid detoxification pathways. Importantly, working with both wild mosquitoes and field circulating parasites, our analysis revealed a strong mosquito genotype by parasite genotype interaction. Our study also identified 51 putative long non-coding RNAs differentially expressed in An. arabiensis mosquito infected midgut. Among these, several mapped to the published An. arabiensis genome at genes coding immune responsive genes such as gambicin 1, leucine-rich repeat containing genes, either on sense or antisense strands. This study constitutes the first comparison of An. arabiensis molecular interaction with P. vivax and P. falciparum, investigating both coding and long non-coding RNAs for the identification of potential transcripts, that could lead to the development of novel approaches to simultaneously block the transmission of vivax and falciparum malaria.

microbiology↗