Kevin Maringer

University of Surrey · Department of Microbial and Cellular Sciences

The number of dengue cases worldwide has increased ten-fold over the past decade as Aedes aegypti, the primary vector of this disease, thrives and expands its distribution, revealing limitations to current control methods. To better understand how Ae. aegypti evolved from a forest dwelling, generalist species to a highly anthropophilic urban specie...

Background Although whole-genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprising...

The mosquito Aedes albopictus transmits human viruses including dengue and chikungunya and is an extremely successful invasive species expanding into new regions of the world. New tools are needed to complement existing tools to help monitor and control this species. Genomic resources are improving for this species including genome reference sequen...

Background Although whole genome sequencing (WGS) is the preferred genotyping method for most genomic analyses, limitations are often experienced when studying genomes characterized by a high percentage of repetitive elements, high linkage, and recombination deserts. The Asian tiger mosquito (Aedes albopictus), for example, has a genome comprised o...

The antiviral role of innate immune responses mediated by the NF-κB family of transcription factors is well established in vertebrates but was for a long time less clear in insects. Insects encode two canonical NF-κB pathways, the Toll and Imd (‘immunodeficiency’) pathways, which are best characterised for their role in antibacterial and antifungal...

Flaviviruses such as dengue virus (DENV) and Zika virus (ZIKV) have evolved sophisticated mechanisms to suppress the host immune system. For instance, flavivirus infections were found to sabotage peroxisomes, organelles with an important role in innate immunity. The current model suggests that the capsid (C) proteins of DENV and ZIKV downregulate p...

Viruses may exploit the cardiovascular system to facilitate transmission or within-host dissemination, and the symptoms of many viral diseases stem at least in part from a loss of vascular integrity. The microvascular architecture is comprised of an endothelial cell barrier ensheathed by perivascular cells (pericytes). Pericytes are antigen-present...

Zika and dengue viruses are emergent arboviruses of great public health impact. Both viruses are responsible for important diseases, yet there is currently no vaccine or specific treatment available.

Mosquitoes are known as important vectors of many arthropod-borne (arbo)viruses causing disease in humans. These include dengue (DENV) and Zika (ZIKV) viruses. The exogenous small interfering (si)RNA (exo-siRNA) pathway is believed to be the main antiviral defense in arthropods, including mosquitoes. During infection, double-stranded RNAs that form...

Background The mosquito Aedes aegypti is a major vector for the arthropod-borne viruses (arboviruses) chikungunya, dengue, yellow fever and Zika viruses. Vector immune responses pose a major barrier to arboviral transmission, and transgenic insects with altered immunity have been proposed as tools for reducing the global public health impact of arb...

The World Health Organization considers dengue one of the top 10 global public health problems. There is no specific antiviral therapy to treat dengue virus and no way of predicting which patients will develop potentially fatal severe dengue, typified by vascular leakage and circulatory shock. We show here that perivascular cells (pericytes) amplif...

The flavivirus dengue virus (DENV) is the most significant arthropod borne virus (arbovirus) of humans, causing serious morbidity and mortality, with nearly half of the world’s population at risk of infection. Due to a lack of antivirals and limited vaccine options, vector control remains a vital defence against dengue disease. The mosquito Aedes a...

Background: The mosquito Aedes aegypti is a major vector for the arthropod-borne viruses (arboviruses) chikungunya, dengue, yellow fever and Zika viruses. Vector immune responses pose a major barrier to arboviral transmission, and transgenic insects with altered immunity have been proposed as tools for reducing the global public health impact of ar...

Dengue is the most prevalent arthropod-borne viral disease affecting humans, with severe dengue typified by potentially fatal microvascular leakage and hypovolaemic shock. Blood vessels of the microvasculature are composed of a tubular structure of endothelial cells ensheathed by perivascular cells (pericytes). Pericytes support endothelial cell ba...

Background Aedes aegypti is a vector mosquito of major public health importance, transmitting arthropod-borne viruses (arboviruses) such as chikungunya, dengue, yellow fever and Zika viruses. Wild mosquito populations are persistently infected at high prevalence with insect-specific viruses that do not replicate in vertebrate hosts. In experimental...

Background Aedes aegypti is a vector mosquito of major public health importance, transmitting arthropod-borne viruses (arboviruses) such as chikungunya, dengue, yellow fever and Zika viruses. Wild mosquito populations are persistently infected at high prevalence with insect-specific viruses that do not replicate in vertebrate hosts. In experimental...

Aedes aegyptiis a vector mosquito of major public health importance, transmitting arthropod-borne viruses (arboviruses) such as chikungunya, dengue, yellow fever and Zika viruses. Wild mosquito populations are persistently infected at high prevalence with insect-specific viruses that do not replicate in vertebrate hosts. In experimental settings, a...

RNA interference (RNAi) controls arbovirus infections in mosquitoes. Two different RNAi pathways are involved in antiviral responses: the PIWI-interacting RNA (piRNA) and exogenous short interfering RNA (exo-siRNA) pathways, which are characterized by the production of virus-derived small RNAs of 25–29 and 21 nucleotides, respectively. The exo-siRN...

PCR primers used in the study. (DOCX)

Immunoprecipitation of siRNA and piRNA pathway proteins. Immunoblot analysis of the immunoprecipitation (IP) samples obtained from Aag2 cell lines infected with ZIKV (MOI 1) 48 h p.i. IP of V5 tagged eGFP, Ago2, Ago3, Piwi5, Piwi6 and Piwi4 was conducted using magnetic beads carrying anti-V5 antibody. (TIF)

Zika-specific small RNA with size 22-24nt. The distribution of 22, 23 or 24 nt long small RNA along the ZIKV genome (red, positive numbers on Y-axis) or antigenome (green, negative numbers on Y-axis). Analysis of total RNA samples isolated from infected Aag2 cells (A) or analysis of RNA bound to Ago3, captured by immunoprecipitation from infected c...

Information regarding small RNA sequencing data. Number of ZIKV-specific sequencing reads obtained by analyzing small RNAs in total cellular RNA samples or in samples that were captured by pulldown of V5-tagged eGFP, Ago2, Ago3, Piwi5, Piwi6 and Piwi4 from Aag2 cells. (DOCX)

Characterization of ZIKV-specific small RNAs captured by Piwi5, Piwi6 or Piwi4. V5-tagged Piwi5 or Piwi6 expressing cells were infected with ZIKV (MOI 1). At 48 hpi they were subjected to immunoprecipitation via V5-tag specific antibody. Analysis of Piwi5 (A) or Piwi6 (B), Piwi4 (C) associated small RNAs indicated the size distribution of those map...

A large proportion of the genome of most eukaryotic organisms consists of highly repetitive mobile genetic elements. The sum of these elements is called the ‘mobilome’, which in eukaryotes is made up mostly of transposons. Transposable elements contribute to disease, evolution, and normal physiology by mediating genetic rearrangement, and through t...

Dengue virus (DENV) is the most prevalent mosquito-borne virus causing human disease. Of the 4 DENV serotypes, epidemiological data suggest that DENV-2 secondary infections are associated with more severe disease than DENV-4 infections. Mass cytometry by time-of-flight (CyTOF) was used to dissect immune changes induced by DENV-2 and DENV-4 in human...

The small interfering RNA (siRNA) pathway is a major antiviral response in mosquitoes; however, another RNA interference pathway, the PIWI-interacting RNA (piRNA) pathway, has been suggested to be antiviral in mosquitoes. Piwi4 has been reported to be a key mediator of this response in mosquitoes, but it is not involved in the production of virus-s...

Zika virus (ZIKV) is a mosquito borne flavivirus, which was a neglected tropical pathogen until it emerged and spread across the Pacific Area and the Americas, causing large human outbreaks associated with fetal abnormalities and neurological disease in adults. The factors that contributed to the emergence, spread and change in pathogenesis of ZIKV...

Background Aedes aegypti is a vector for the (re-)emerging human pathogens dengue, chikungunya, yellow fever and Zika viruses. Almost half of the Ae. aegypti genome is comprised of transposable elements (TEs). Transposons have been linked to diverse cellular processes, including the establishment of viral persistence in insects, an essential step i...

Viral protein homeostasis depends entirely on the machinery of the infected cell. Accordingly, viruses can illuminate the interplay between cellular proteostasis components and their distinct substrates. Here, we define how the Hsp70 chaperone network mediates the dengue virus life cycle. Cytosolic Hsp70 isoforms are required at distinct steps of t...

Aedes aegypti is an important mosquito vector for a number of emerging or re-emerging arboviruses of global public health importance, including dengue virus, yellow fever virus, and chikungunya virus. Although the Ae. aegypti genome has been sequenced, gaps and poorly-sequenced regions remain in the genome, and genome annotation is incomplete. This...

STING has emerged in recent years as an important signalling adaptor in the activation of type I interferon responses during infection with DNA viruses and bacteria. An increasing body of evidence suggests that STING also modulates responses to RNA viruses, though the mechanisms remain less clear. In this review, we give a brief overview of the way...

Assembly of the herpesvirus tegument is poorly understood but is believed to involve interactions between outer tegument proteins and the cytoplasmic domains of envelope glycoproteins. Here we present the detailed characterisation of a multicomponent glycoprotein-tegument complex found in herpes simplex virus type 1 (HSV1) infected cells. We demons...

Dengue virus (DENV) is a pathogen with a high impact on human health. It replicates in a wide range of cells involved in the immune response. To efficiently infect humans, DENV must evade or inhibit fundamental elements of the innate immune system, namely the type I interferon response. DENV circumvents the host immune response by expressing protei...

Although the herpes simplex virus type 1 (HSV-1) tegument is comprised of a large number of viral and cellular proteins, how and where in the cell these proteins are recruited into the virus structure is poorly understood. We have shown previously that the immediate-early gene product ICP0 is packaged by a mechanism dependent on the major tegument...

The mechanism by which herpesviruses acquire their tegument is not yet clear. One model is that outer tegument proteins are recruited by the cytoplasmic tails of viral glycoproteins. In the case of herpes simplex virus tegument protein VP22, interactions with the glycoproteins gE and gD have been shown. We have previously shown that the C-terminal...