van Oers, M. M. | Search bioRxiv

bioRxiv2021

An adaptive compromise - Conflicting evolutionary pressures on arthropod borne Zika virus dinucleotide composition in mammalian hosts and mosquito vectors

Most vertebrate RNA viruses show pervasive suppression of CpG and UpA dinucleotides, closely resembling the dinucleotide composition of host cell transcriptomes. In contrast, CpG suppression is absent in both invertebrate mRNA and RNA viruses that exclusively infect arthropods. Arthropod-borne (arbo) viruses are transmitted between vertebrate hosts by invertebrate vectors and thus encounter potentially conflicting evolutionary pressures in the different cytoplasmic environments. Using a newly developed Zika virus (ZIKV) model, we have investigated how demands for CpG suppression in vertebrate cells can be reconciled with potentially quite different compositional requirements in invertebrates, and how this affects ZIKV replication and transmission. Mutant viruses with synonymously elevated CpG or UpA dinucleotide frequencies showed attenuated replication in vertebrate cell lines, which was rescued by knockout of the zinc-finger antiviral protein (ZAP). Conversely, in mosquito cells, ZIKV mutants with elevated CpG dinucleotide frequencies showed substantially enhanced replication compared to wildtype. Host-driven effects on virus replication attenuation and enhancement were even more apparent in mouse and mosquito models. Infections with CpG-or UpA-high ZIKV mutants in mice did not cause typical ZIKV-induced tissue damage and completely protected mice during subsequent challenge with wildtype virus, which demonstrates their potential as live-attenuated vaccines. In contrast, the CpG-high mutants displayed enhanced replication in Aedes aegypti mosquitoes and a larger proportion of mosquitoes carried infectious virus in their saliva. These findings show that mosquito cells are also capable of discriminating RNA based on dinucleotide composition. However, the evolutionary pressure on the CpG dinucleotides of viral genomes in arthropod vectors directly opposes the pressure present in vertebrate host cells, which provides evidence that an adaptive compromise is required for arbovirus transmission. This suggests that the genome composition of arthropod-borne flaviviruses is crucial to maintain the balance between high-level replication in the vertebrate host and persistent replication in the mosquito vector.

microbiology↗

bioRxiv2020

A new automated chilled adult release system for the aerial distribution of sterile male tsetse flies

BackgroundTsetse flies transmit trypanosomes that cause the debilitating diseases human African trypanosomosis (HAT) or sleeping sickness in humans and animal African trypanosomosis (AAT) or nagana in livestock. The riverine tsetse species Glossina palpalis gambiensis Vanderplank (Diptera: Glossinidae) inhabits riparian forests along river systems in West Africa. The Government of Senegal has embarked on a project to eliminate a population of this tsetse species from the Niayes area with the objective to manage AAT in this area. The project is implemented following an area-wide integrated pest management approach with an SIT component. The SIT can only be successful when the sterile males that are released in the field are of high biological quality, i.e. have the same dispersal capacity, survival and competitiveness as their wild counterparts. To date, sterile tsetse males have been released by air using biodegradable cardboard cartons that were manually dropped from a fixed-wing aircraft or gyrocopter. The cardboard boxes are however expensive, and the system is rather cumbersome to implement. MethodsA new prototype of an automated chilled adult release system (Bruno Spreader Innovation, (BSI)) for tsetse flies was tested for its accuracy (in counting numbers of sterile males as loaded into the machine), release rate consistency and impact on quality of the released males. The impact of the release process was evaluated on several performance indicators of the irradiated male flies such as flight propensity, survival, mating competitiveness, premating and mating duration, and insemination rate of mated females. ResultsThe BSI release system counted with a consistent accuracy and released homogenously tsetse flies at the lowest motor speed (0.6 rpm). In addition, the chilling conditions (6 {+/-} 1 {degrees}C) and the release process (passing of flies through the machine) had no significant negative impact on the males flight propensity. No significant differences were observed between the control males (no irradiation and no exposure to the release process), irradiated males (no exposure to the release process) and irradiated males exposed to the release process with respect to mating competitiveness, premating period and mating duration. Only survival of irradiated males that were exposed to the release process was reduced ([~]2 folds), irrespective of whether the males were held with or without feeding. ConclusionAlthough the release process had a negative effect on survival of the flies, the data of the experiments indicate that the BSI machine holds promise for use in tsetse SIT programmes. The results of this study will now need to be confirmed under operational field conditions in West Africa.

pathology↗