Biology subjects

Matthijnssens, J.

Publications and source records attributed to Matthijnssens, J..

21 records · Page 2Linked to original sources

bioRxiv2020

The conservation of a core virome in Aedes mosquitoes across different developmental stages and continents

Mosquitoes belonging to the genus Aedes can efficiently transmit many pathogenic arboviruses, placing a great burden on public health worldwide. In addition, they also carry a number of insect specific viruses (ISVs), and it was recently suggested that some of these ISVs might form a stable species-specific "core virome" in mosquito populations. However, little is known about such a core virome in laboratory colonies and if it is present across different developmental stages. In this study, we compared the viromes in eggs, larvae, pupae and adults of Aedes albopictus mosquitoes collected from the field as well as from a lab colony. The virome in lab-derived Ae. albopictus is very stable across all stages, consistent with a vertical transmission route of these viruses, forming a "vertically transmitted core virome". The different stages of field collected Ae. albopictus mosquitoes also contains this stable vertically transmitted core virome as well as another set of viruses shared by mosquitoes across different stages, which might be an "environment derived core virome". Both these vertically and environmentally transmitted core viromes in Ae. albopictus deserve more attention with respect to their effects on vector competence for important medically relevant arboviruses. To further study this core set of ISVs, we screened 46 publically available SRA viral metagenomic dataset of mosquitoes belonging to the genus Aedes. Some of the identified core ISVs are identified in the majority of SRAs. In addition, a novel virus, Aedes phasmavirus, is found to be distantly related to Yongsan bunyavirus 1, and the genomes of the core virus Phasi Charoen-like phasivirus is highly prevalent in the majority of the tested samples, with nucleotide identities ranging from 94% to 99%. Finally, Guadeloupe mosquito virus, and some related viruses formed three separated phylogenetic clades. How these core ISVs influence the biology of mosquito host, arboviruses infection and evolution deserve to be further explored.

microbiology↗

bioRxiv2020

Assessing the in vitro resistance development in Enterovirus 71 in the context of combination antiviral treatment

There are currently no antivirals available to treat infection with enterovirus A71 (EV-A71) or any other enterovirus. The extensively studied capsid binders select rapidly for drug-resistant variants. We here explore whether the combination of two direct-acting enterovirus inhibitors with a different mechanism of action may delay or prevent resistance development to the capsid binders. To that end, the in vitro dynamics of resistance development to the capsid binder pirodavir was studied either alone or in combination with (i) a viral 2C-targeting compound (SMSK_0213), (ii) a viral 3C-protease inhibitor (rupintrivir) or (iii) a viral RNA-dependent RNA polymerase (RdRp) inhibitor [7-deaza-2C-methyladenosine (7DMA)]. We demonstrate that combining pirodavir with either rupintrivir or the nucleoside analogue 7DMA delays the development of resistance to pirodavir and that no resistance to the protease or polymerase inhibitor develops. The combination of pirodavir with the 2C inhibitor results in a double-resistant virus population. The deep sequencing analysis of resistant populations revealed that even though resistant mutations are present in less than 30% of the population, this still provides the resistant phenotype.

microbiology↗

bioRxiv2019

A robust human norovirus replication model in zebrafish larvae

Human noroviruses (HuNoVs) are an important cause of epidemic and endemic acute gastroenteritis worldwide; annually about 700 million people develop a HuNoV infection resulting in [~]219,000 deaths and a societal cost estimated at 60 billion US dollars 1. The lack of robust small animal models has significantly hindered the understanding of norovirus biology and the development of effective therapeutics against HuNoV. Here we report that HuNoV GI and GII replicate to high titers in zebrafish (Danio rerio) larvae; replication peaks at day 2 post infection and is detectable for at least 6 days. HuNoV is detected in cells of the hematopoietic lineage, the intestine, liver and pancreas. Antiviral treatment reduces HuNoV replication by >2 log10, showing that this model is suited for antiviral studies. Downregulation of fucosyltransferase 8 (fut8) in the larvae reduces HuNoV replication, highlighting a common feature with infection in humans. Zebrafish larvae constitute a simple and robust replication model that will largely facilitate studies of HuNoV biology and the development of antiviral strategies.

microbiology↗