Arthropod-borne viruses (arboviruses) are naturally maintained in an enzootic (sylvatic) cycle in which virus is transmitted during blood-feeding between arthropod vectors and amplifying vertebrate hosts. Human infections can be caused by spill-over infections or by viral adaptation to anthropophilic mosquito species and to humans as host. Evolution of such an urban transmission cycle is associated with greatly increased epidemic potential of arboviruses. With the increasing global spread of arboviruses, it is important to understand the factors that affect virus transmission by mosquitoes and to predict the potential to arboviruses to emerge into epidemic cycles. 

RNA interference (RNAi) is an important antiviral mechanism in insects, including the major vector mosquitoes, and many insect viruses evolved counter-defense mechanisms to suppress RNAi. The aim of the first funding period was to understand the role of RNAi in Flavivirus virus infection of mosquitoes. We established robust assays to identify RNAi suppressors in mosquito viruses. Using these assays, we were unable to identify RNAi suppressors in a broad panel of flavivirus family members, including mosquito-specific viruses and mosquito-borne arboviruses. We analyzed viral small RNA profiles using deep-sequencing technology and found that Culex and Aedes-tropic viruses in Aedes cells produce similar levels of small RNAs. Surprisingly in two of the analyzed members of flaviviruses we found, in addition to the production of virus-derived small interfering RNAs (siRNA) evidence for the production of small RNAs with the characteristics of piwi-associated RNAs (piRNA). 

The overall aim of this project is to understand the role of antiviral RNAi responses and viral counter-defense in establishing vector competence in mosquitoes. We will compare the induction and suppression of RNAi among representatives of the Bunyaviridae family that differ in their mode of transmission, vector tropism, and sylvatic or epidemic origin, as a parallel example to the Flaviviridae that were analyzed in the first funding period. Moreover, we will analyze small RNAs from naturally infected mosquitoes and viral RNAi suppression of novel viruses that are identified in an ecological survey of wild-caught mosquitoes within the framework of SPP1596.

Arboviruses are an important group of human and animal pathogens and their emergence and re-emergence requires thorough understanding of vector transmission. This proposal will have a major impact on our understanding of vector competence. Furthermore, our results will contribute to our ability to predict the ability of arboviruses to cross the species barrier and the potential of known and novel sylvatic arboviruses to transfer into epidemic amplification cycles. 

In cooperation with Prof. Ronald van Rij (Radboud University Nijmegen Medical Centre, the Netherlands)

Funded by DFG Priority Program ‘Ecology and species barriers in emerging viral diseases’ (SPP 1596, Junglen JU 2857/1-2)

Despite considerable research efforts during recent years, still very little is known about fundamental ecological mechanisms driving virus prevalence, evolutionary potential and emergence from wildlife reservoirs in general. Holistic approaches integrating host and viral traits are required to understand the dynamics and drivers of virus infections. This collaborative, multi-taxa project investigates the impact of anthropogenic habitat disturbance on host community composition, abundance pattern and immune genetic constitution of generalist species and relates the obtained data to local virus prevalence. Our aim is to identify ecological, behavioral and genetic constraints associated with virus evolution under the hypothesis of the dilution effect. We are focusing on three major viral vertebrate host taxa - bats, rodents and marsupials -, as well as on putatively blood-feeding mosquito vectors. Whereas our focus in the first funding period was on taking baseline data and parameter correlations, we will shift in the second period to ecological validation, ecological modeling and network analyses of host-virus systems in order to investigate the development and dynamics of virus mutation hotspots in disturbed landscapes. The central task will be to understand the processes and mechanisms that determine how biodiversity loss and shifts in species abundance of resilient, less sensitive species modulate virus ecology and lead to an increased prevalence and diversification of emerging pathogens within native animal communities.

 In cooperation with Prof. Simone Sommer, Prof. Marco Tschapka (University of Ulm), Prof. Dr. Gerald Kerth (University of Greifswald)

Funded by DFG Priority Program ‘Ecology and species barriers in emerging viral diseases’ (SPP 1596, Junglen JU 2857/3-2)

Vector-borne diseases account for an estimated 17% of infectious diseases and cause more than 1 million deaths annually. RNA viruses, transmitted by blood-feeding arthropods (arboviruses), pose a particularly high risk as they can easily spread to new geographic regions where they may cause serious epidemics in naïve populations, such as by Zika-, chikungunya-, dengue- and Rift Valley fever viruses. Despite this high relevance, little is known about enzootic maintenance cycles and prevalence even for medically important arboviruses in the African countries of origin. Moreover, research of transmission cycles has mainly been focused on the role of mosquitoes as arboviral vectors. Other blood-feeding arthropods, such as ticks, biting midges and sandflies, have received considerable less attention. Relevant agents like Schmallenberg virus, Crimean-Congo hemorrhagic fever virus and phleboviruses are transmitted by these vectors.

Situated at one of the most renowned African entomology institutes, this collaborative project aims at a comprehensive understanding of key arboviral diseases in Kenya, including the virus sources, the infection-related impacts on humans, as well as the societal conditions and consequences of arbovirus disease. A strong focus in all stages of research will be on training and capacity building for future independent work in an African research environment. The research will have a local and exemplary focus to enable efficient training and technology transfer, but will provide important outcomes due to the setting of the work in one of the key seeding regions of arbovirus diseases globally.

The key objectives are (i) to study the disease ecology of relevant arboviruses in blood-feeding vectors, livestock and peri-domestic wildlife, (ii) to determine the impact of arboviral disease on human health and local society, involving complementary approaches from the fields of laboratory-based epidemiology and social sciences, and (iii) to provide training, education, and well-targeted capacity building in disease ecology, veterinary medicine and agro-social sciences, as well as virology.

The generated data will promote the local control of key arboviral diseases and thereby limit the risk of spread of indigenous arboviruses to new geographic regions. 

In cooperation with Prof. Christian Borgemeister (Centre for Development Research, Bonn), Prof. Rosemary Sang (Kenya Medical Research Institute and International Centre of Insect Physiology and Ecology, Nairobi, Kenya), Prof. Baldwyn Torto, Dr. David Tchouassi (International Centre of Insect Physiology and Ecology, Nairobi, Kenya)

Funded by the DFG (Junglen JU 2857/9-1)

(Part of the Collaborative Research Center 228: Future Rural Africa: Future-making and social-ecological transformation; www.futureruralafrica.de and www.crc228.de). 

Conservation and intensification are two important pathways of large-scale land-use change in rural Africa. Besides anticipated effects, these top-down strategies of future-making may have unintended side effects, in particular because of so called emerging infectious diseases (EIDs). These pose a serious threat to global health, and among the latter a significant number are arthropod-borne viruses, so-called arboviruses. Arboviruses are particularly sensitive to ecological changes and can easily escape from their natural transmission cycles and adapt to new hosts and geographic regions. Most prominent examples are the epidemics caused by yellow fever, Dengue, Chikungunya and Zika viruses in humans and Rift Valley fever (RVF) in both humans and animals. Land-use changes can have profound effects on biodiversity and EIDs. However, functional linkages between biodiversity and viral pathogens are poorly understood. Moreover, land-use, climatic and demographic changes and rapidly developing livestock markets with concurrent social transformations have a tremendous impact on the livestock sector, in particular on traditional forms of pastoralism in Africa. Yet the impact of ongoing socio-ecological transformations in rural Africa on arbovirus transmission cycles remains elusive. This project aims to understand how ecosystem diversity influences vector and virus populations in the light of large-scale land use changes in rural Africa. Effects of conservation and agricultural intensification (with a particular focus on invasive plant species) on selected arboviruses will be studied in the KAZA and the KRV sites. We will analyze major ecosystem characteristics and assess vector diversity and concomitant arbovirus infections at sites with different duration of land-use changes, the latter especially in KAZA. To identify if simple proxies of diversity can predict patterns of arbovirus abundance or prevalence, we will quantify the taxonomic diversity of vectors, hosts and vegetation. The latter could be important, as there are indications that some vector species favor certain invasive plants. Thus, this project will attempt to quantify the proportion of selected invasive plants, initially in the KRV site, and analyze the impact on vector dynamics and arbovirus prevalence. Close collaboration with projects studying agricultural futures (A03) and conservation areas (A04), ecosystem diversity and services (A01), the challenges of invasive species (B01), and the economic and energy transformations (C02) to name a few will enable a broad and long-term understanding on how such socio-ecological changes will affect arboviral diseases at the KAZA and KRV sites. 

In collaboration with Prof. Dr. Christian Borgemeister, Center for Development Research (ZEF), University of Bonn, Bonn, Germany; Dr. David Tchouassi, International Centre of Insect Physiology and Ecology (icipe), Nairobi, Kenya; Dr. Rosemary Sang, Kenya Medical Research Institute, Nairobi, Kenya; Dr. John Mfune, Head of the Department of Biological Sciences, University of Namibia (UNAM), Namibia

Funded by the DFG Collaborative Research Center 228. 

Vector-borne infections account for about one fifth of all infectious diseases. Especially mosquito-borne viruses that often originate in tropical areas manage to spread to new hosts or new geographic regions with relative ease. However, our knowledge of arbovirus diversity, evolution, and geographic spread is mainly based on epidemic variants. To fill critical gaps in our knowledge on pre-epidemic viruses and viral emergence, we will characterize arbovirus diversity along tropical disturbance gradients to document and dissect microevolutionary processes in viral habitat expansion.

The overall aims of the group are: (i) to provide a comprehensive sample of mosquitoes from ecologically undisturbed and adjacent disturbed habitats in three main tropical rainforest ecosystem types occurring in Africa. We will characterise the true taxonomic diversity of arthropod-associated viruses including novel prototypic deep lineages still existing in natural ecosystems using state of the art methods; (ii) to identify the interplay between host community composition and viral emergence processes using mosquito-associated viruses as a multi-host and multi-pathogen system; and (iii) to analyse whether and how arbovirus emergence is driven by positive selection involving fitness gains of emergent strains using genetic and phenotypic viral population studies. Taken together we will obtain the first comprehensive assessment of viral microevolution during emergence in a real-world scenario.

Funded by the Federal Ministry of Education and Research (BMBF, Junglen 01KI1716)