Glycosaminoglycan binding by arboviruses: a cautionary tale.

Arboviruses are medically important arthropod-borne viruses that cause a range of diseases in humans from febrile illness to arthritis, encephalitis and hemorrhagic fever. Given their transmission cycles, these viruses face the challenge of replicating in evolutionarily divergent organisms that can include ticks, flies, mosquitoes, birds, rodents, reptiles and primates. Furthermore, their cell attachment receptor utilization may be affected by the opposing needs for generating high and sustained serum viremia in vertebrates such that virus particles are efficiently collected during a hematophagous arthropod blood meal but they must also bind sufficiently to cellular structures on divergent organisms such that productive infection can be initiated and viremia generated. Sulfated polysaccharides of the glycosaminoglycan (GAG) groups, primarily heparan sulfate (HS), have been identified as cell attachment moieties for many arboviruses. Original identification of GAG binding as a phenotype of arboviruses appeared to involve this attribute arising solely as a consequence of adaptation of virus isolates to growth in cell culture. However, more recently, naturally circulating strains of at least one arbovirus, eastern equine encephalitis, have been shown to bind HS efficiently and the GAG binding phenotype continues to be associated with arbovirus infection in published studies. If GAGs are attachment receptors for many naturally circulating arboviruses, this could lead to development of broad-spectrum antiviral therapies through blocking of the virus-GAG interaction. This review summarizes the available data for GAG/HS binding as a phenotype of naturally circulating arbovirus strains emphasizing the importance of avoiding tissue culture amplification and artifactual phenotypes during their isolation.

Spatial Distribution and Burden of Emerging Arboviruses in French Guiana.

Despite the health, social and economic impact of arboviruses in French Guiana, very little is known about the extent to which infection burden is shared between individuals. We conducted a large multiplexed serological survey among 2697 individuals from June to October 2017. All serum samples were tested for IgG antibodies against DENV, CHIKV, ZIKV and MAYV using a recombinant antigen-based microsphere immunoassay with a subset further evaluated through anti-ZIKV microneutralization tests. The overall DENV seroprevalence was estimated at 73.1% (70.6-75.4) in the whole territory with estimations by serotype at 68.9% for DENV-1, 38.8% for DENV-2, 42.3% for DENV-3, and 56.1% for DENV-4. The overall seroprevalence of CHIKV, ZIKV and MAYV antibodies was 20.3% (17.7-23.1), 23.3% (20.9-25.9) and 3.3% (2.7-4.1), respectively. We provide a consistent overview of the burden of emerging arboviruses in French Guiana, with useful findings for risk mapping, future prevention and control programs. The majority of the population remains susceptible to CHIKV and ZIKV, which could potentially facilitate the risk of further re-emergences. Our results underscore the need to strengthen MAYV surveillance in order to rapidly detect any substantial changes in MAYV circulation patterns.

Prevalence of arbovirus antibodies in young healthy adult population in Brazil.

BACKGROUND: The emergence and re-emergence of infectious diseases are a cause for worldwide concern. The introduction of Zika and Chikungunya diseases in the Americas has exposed unforeseen medical and logistical challenges for public health systems. Moreover, the lack of preventive measures and vaccination against known and emerging mosquito-transmitted pathogens, and the occurrence of unanticipated clinical complications, has had an enormous social and economic impact on the affected populations. In this study, we aimed to measure the seroprevalence of endemic and emerging viral pathogens in military personnel stationed in Manaus, Amazonas state. METHODS: We measured the seropositivity of antibodies against 19 endemic and emerging viruses in a healthy military personnel group using a hemagglutination inhibition assay (HIA). RESULTS: Overall, DENV positivity was 60.4%, and 30.9% of the individuals reacted against ZIKV. Also, 46.6%, 54.7%, 51.3% and 48.7% individuals reacted against West Nile virus (WNV), Saint Louis encephalitis virus (SLEV), Ilheus virus (ILHV) and Rocio virus (ROCV), respectively. Individuals with high DENV HIA titer reacted more frequently with ZIKV or WNV compared to those with low HIA titers. Observed cross-reactivity between Flaviviruses varied depending on the virus serogroup. Additionally, 0.6% and 0.3% individuals were seropositive for Oropouche virus (OROV) and Catu virus (CATUV) from the family Peribunyaviridae, respectively. All samples were negative for Eastern Equine Encephalitis virus (EEEV), Western Equine Encephalomyelitis virus (WEEV), Mayaro virus (MAYV), Mucambo virus (MUCV) and CHIKV from the family Togaviridae. CONCLUSIONS: A high proportion of individuals in our high-risk population (~ 60%) lacked antibodies against major endemic and emerging viruses, which makes them susceptible for further infections. Military personnel serving in the Amazon region could serve as sentinels to strengthen global infectious disease surveillance, particularly in remote areas.

Seroprevalence of arboviruses in Ecuador: Implications for improved surveillance. / Seroprevalencia de arbovirus en Ecuador: implicaciones para mejorar su vigilancia

INTRODUCTION: Arthropod-borne viruses (arboviruses) cause morbidity and mortality in humans and domestic animals worldwide. The percentage of population immunity or susceptibility to these viruses in Ecuador is unknown. OBJECTIVES: To investigate the proportion of Ecuadorian populations with IgG antibodies (Abs) (past exposure/immunity) and IgM Abs (current exposure) against flaviviruses and alphaviruses and to study the activity of these viruses in Ecuador. MATERIALS AND METHODS: During 2009-2011, we conducted a serosurvey for selected arboviruses in humans (n=1,842), equines (n=149), and sentinel hamsters (n=84) at two coastal locations and one in the Amazon basin (Eastern Ecuador) using enzyme-linked immunosorbent assay and hemagglutination inhibition test. RESULTS: From 20.63% to 63.61% of humans showed IgG-antibodies for the flaviviruses: Dengue virus (DENV), yellow fever virus (YFV) Saint Louis encephalitis virus, and West Nile virus (WNV); from 4.67% to 8.63% showed IgG-Abs for the alphaviruses: Venezuelan equine encephalitis virus, eastern equine encephalitis virus, and western equine encephalitis virus. IgM-Abs were found for DENV and WNV. Equines and hamsters showed antibodies to alphaviruses in all locations; two hamsters seroconverted to YFV in the Amazonia. CONCLUSIONS: The results show a YFV vaccination history and suggest the activity of arboviruses not included in the current surveillance scheme. Enhanced arbovirus and mosquito surveillance, as well as continued YFV vaccination and evaluation of its coverage/effectiveness, are recommended.

Introducción. Los virus transmitidos por artrópodos (arbovirus) causan morbilidad y mortalidad en humanos y animales domésticos mundialmente. Se desconoce el porcentaje de inmunidad o vulnerabilidad de la población ecuatoriana ante estos virus. Objetivos. Investigar la proporción de poblaciones ecuatorianas con anticuerpos IgG (exposición o inmunidad pasada) y anticuerpos IgM (exposición reciente) contra flavivirus y alfavirus, e investigar su actividad en Ecuador. Materiales y métodos. Entre 2009 y 2011, se llevó a cabo una encuesta serológica para arbovirus en humanos (n=1.842), equinos (n=149) y hámsters centinela (n=84) en dos localidades costeras y en una en la Amazonía, utilizando la prueba ELISA (Enzyme-Linked ImmunoSorbent Assay) y la prueba de inhibición de la hemaglutinación. Resultados. Entre el 20,63 y el 63,61 % de los humanos registraron IgG contra el virus del dengue (DENV), el de la fiebre amarilla (YFV), el de la encefalitis de San Luis y el del Nilo Occidental (WNV); entre 4,67 y 8,63 % tenían IgG para los virus de la encefalitis equina venezolana, de la encefalitis equina del este y de la encefalitis equina del oeste. Se encontró IgM para DENV y WNV. En los equinos y en los hámsters se encontraron anticuerpos contra alfavirus en todas las localidades muestreadas; dos hámsters mostraron seroconversión a YFV en la Amazonía. Conclusiones. Los resultados del estudio evidenciaron los antecedentes de vacunación contra el YFV y sugieren la actividad de arbovirus no incluidos en el esquema de vigilancia actual. Se recomienda ampliar la vigilancia de arbovirus y mosquitos, continuar con la vacunación contra el YFV, y evaluar su cobertura y efectividad.

Sphingomyelinases in a journey to combat arthropod-borne pathogen transmission.

Ixodes scapularis ticks feed on humans and other vertebrate hosts and transmit several pathogens of public health concern. Tick saliva is a complex mixture of bioactive proteins, lipids and immunomodulators, such as I. scapularis sphingomyelinase (IsSMase)-like protein, an ortholog of dermonecrotoxin SMase D found in the venom of Loxosceles spp. of spiders. IsSMase modulates the host immune response towards Th2, which suppresses Th1-mediated cytokines to facilitate pathogen transmission. Arboviruses utilize exosomes for their transmission from tick to the vertebrate host, and exosomes derived from tick saliva/salivary glands suppress C-X-C motif chemokine ligand 12 and interleukin-8 immune response(s) in human skin to delay wound healing and repair processes. IsSMase affects also viral replication and exosome biogenesis, thereby inhibiting tick-to-vertebrate host transmission of pathogenic exosomes. In this review, we elaborate on exosomes and their biogenesis as potential candidates for developing novel control measure(s) to combat tick-borne diseases. Such targets could help with the development of an efficient anti-tick vaccine for preventing the transmission of tick-borne pathogens.

Experimental Challenge of Sheep and Cattle with Dugbe Orthonairovirus, a Neglected African Arbovirus Distantly Related to CCHFV.

Dugbe orthonairovirus (DUGV) is a tick-borne arbovirus within the order Bunyavirales. DUGV was first isolated in Nigeria, but virus isolations in ten further African countries indicate that DUGV is widespread throughout Africa. Humans can suffer from a mild febrile illness, hence, DUGV is classified as a biosafety level (BSL) 3 agent. In contrast, no disease has been described in animals, albeit serological evidence exists that ruminants are common hosts and may play an important role in the transmission cycle of this neglected arbovirus. In this study, young sheep and calves were experimentally inoculated with DUGV in order to determine their susceptibility and to study the course of infection. Moreover, potential antibody cross-reactivities in currently available diagnostic assays for Crimean-Congo hemorrhagic fever orthonairovirus (CCHFV) were assessed as DUGV is distantly related to CCHFV. Following subcutaneous inoculation, none of the animals developed clinical signs or viremia. However, all ruminants seroconverted, as demonstrated by two DUGV neutralization test formats (micro-virus neutralization test (mVNT), plaque reduction (PRNT)), by indirect immunofluorescence assays and in bovines by a newly developed DUGV recombinant N protein ELISA. Sera did not react in commercial CCHFV ELISAs, whereas cross-reactivities were observed by immunofluorescence and immunoblot assays.

Encephalitic Arboviruses of Africa: Emergence, Clinical Presentation and Neuropathogenesis.

Many mosquito-borne viruses (arboviruses) are endemic in Africa, contributing to systemic and neurological infections in various geographical locations on the continent. While most arboviral infections do not lead to neuroinvasive diseases of the central nervous system, neurologic diseases caused by arboviruses include flaccid paralysis, meningitis, encephalitis, myelitis, encephalomyelitis, neuritis, and post-infectious autoimmune or memory disorders. Here we review endemic members of the Flaviviridae and Togaviridae families that cause neurologic infections, their neuropathogenesis and host neuroimmunological responses in Africa. We also discuss the potential for neuroimmune responses to aide in the development of new diagnostics and therapeutics, and current knowledge gaps to be addressed by arbovirus research.

Application of Aptamer-Based Assays to the Diagnosis of Arboviruses Important for Public Health in Brazil.

Arbovirus infections represent a global public health problem, and recent epidemics of yellow fever, dengue, and Zika have shown their critical importance in Brazil and worldwide. Whilst a major effort for vaccination programs has been in the spotlight, a number of aptamer approaches have been proposed in a complementary manner, offering the possibility of differential diagnosis between these arboviruses, which often present similar clinical symptoms, as well as the potential for a treatment option when no other alternative is available. In this review, we aim to provide a background on arbovirus, with a basic description of the main viral classes and the disease they cause, using the Brazilian context to build a comprehensive understanding of their role on a global scale. Subsequently, we offer an exhaustive revision of the diagnostic and therapeutic approaches offered by aptamers against arboviruses. We demonstrate how these promising reagents could help in the clinical diagnosis of this group of viruses, their use in a range of diagnostic formats, from biosensors to serological testing, and we give a short review on the potential approaches for novel aptamer-based antiviral treatment options against different arboviral diseases.

Diabetes insípida y virus del Zika / Diabetes insipid us and Zika virus

La diabetes insípida es el resultado de una secreción o acción reducidas de la hormona vasopresina, expresada clínicamente por un cuadro de poliuria-polidipsia. Los arbovirus pueden tener afinidad por el sistema nervioso y se ha demostrado que el Zika desencadena un trastorno autoinmune que ataca a las células nerviosas, lo que puede traer como consecuencia una diabetes insípida central. En la literatura médica nacional e internacional revisada no se reportan casos anteriores donde se vincule la diabetes insípida con el virus del Zika. Se presenta un caso a propósito de esta asociación: paciente femenina de 53 años, diagnosticada con infección por el virus del Zika dos semanas antes de comenzar con los síntomas sugestivos de diabetes insípida. El potencial neurotrópico del virus, así como los resultados en la resonancia magnética nuclear y la determinación de marcadores de autoinmunidad anti-ADNdc positivos, son elementos que apoyan la hipótesis de que la paciente presentó una posible hipofisitis autoinmune, como respuesta inflamatoria post-infección, desarrollando diabetes insípida central transitoria(AU)

Diabetes insipidus is the result of reduced secretion or action of the vasopressin hormone, which is clinically expressed by a polyuria-polydipsia picture. Arboviruses can have a nervous system affinity and Zika has been shown to trigger an autoimmune disorder that attacks nerve cells, which can result in central diabetes insipidus. The reviewed national and international medical literatures does not report previous cases linking diabetes insipidus with Zika virus. It is presented a case about this association: 53-year-old female patient diagnosed with Zika virus infection two weeks before starting symptoms suggestive of diabetes insipidus. The neurotropic potential of the virus, as well as the results in nuclear MRI and the determination of positive anti-ADNdc autoimmunity markers are elements that support the hypothesis that the patient had a possible autoimmune hypophysis, as a post-infection inflammatory response, developing transient central diabetes insipidus(AU)

Low Incidence and Mortality from SARS-CoV-2 in Southern Europe. Proposal of a hypothesis for Arthropod borne Herd immunity.

SARS-CoV-2 incidence and mortality in Europe have shown wide variation. Northern Italy in particular the Lombardy region, north-eastern French regions, Switzerland and Belgium were amongst the hardest hit, while the central and southern Italian regions, all the Balkan countries from Slovenia to Greece and the Islands of Malta and Cyprus had much fewer cases and deaths per capita, and deaths per number of cases. Differences in public health measures, and health care delivery, in the author's opinion, can only partly explain the difference. The geographical distribution of Phlebotomus sand-flies and the relative distribution of arthropod borne diseases Leishmaniasis and Phlebovirus infections especially the Sicilian Sandfly fever group corresponds to most areas of low prevalence of SARS-CoV-2. A hypothesis is proposed whereby repeated arthropod or sandfly vector infection of humans by novel viruses of zoonotic origins carrying bat or mammalian RNA/DNA, such as phleboviruses may have resulted in the development of an effective evolutionary immune response to most novel zoonotic viruses such as SARS-CoV-2 by means of survival of the fittest possibly over many generations. This process probably ran in parallel and concurrent with the progressive evolution of novel coronaviruses which spread from one mammalian species to another. Other possible, but less likely mechanisms for the role of sandfly meals within a much shorter time frame may have led to, (i) previous exposure and infection of humans with the SARS-Cov-2 virus itself, or a closely related corona virus in the previous decades, or (ii) exposure of human populations to parts coronavirus protein namely either S or more likely N protein carried mechanically by arthropods, but without clinical disease causing direct immunity or (iii) by causing infection with other arthropod borne viruses which could carry bat DNA/RNA and have similar functional proteins resulting in an immediate cross-reactive immune response rather than by natural selection. The Evidence possibly supporting or disputing this hypothesis is reviewed, however the major problem with the hypothesis is that to date no coronavirus has ever been isolated from arthropods. Such a hypothesis can only be supported by research investigating the possible biological relationship of arthropods and coronaviruses where paradoxically they may be promoting immunity rather than disease.

Serologic Evidence of Arthropod-Borne Virus Infections in Wild and Captive Ruminants in Ontario, Canada.

Arthropod-borne viruses (arboviruses) are globally widespread, and their transmission cycles typically involve numerous vertebrate species. Serologic testing of animal hosts can provide a routine surveillance approach to monitoring animal disease systems, can provide a surveillance alternative to arthropod testing and human case reports, and may augment knowledge of epizootiology. Wild and captive ruminants represent good candidate sentinels to track geographic distribution and prevalence of select arboviruses. They often are geographically widespread and abundant, inhabit areas shared by humans and domestic animals, and are readily fed on by various hematophagous arthropod vectors. Ontario, Canada, is home to high densities of coexisting humans, livestock, and wild cervids, as well as growing numbers of arthropod vectors because of the effects of climate change. We collected blood samples from 349 livestock (cattle/sheep) and 217 cervids (wild/farmed/zoo) in Ontario (2016-2019) to assess for antibodies to zoonotic and agriculturally important arboviruses. Livestock sera were tested for antibodies to bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV). Sera from cervids were tested for antibodies to BTV, EHDV, West Nile virus (WNV), eastern equine encephalitis virus (EEEV), Powassan virus (POWV), and heartland virus (HRTV). Fifteen (9.0%) cattle were seropositive for EHDV-serotype 2. Nine (4.2%) cervids were seropositive for arboviruses; three confirmed as WNV, three as EEEV, and one as POWV. All animals were seronegative for BTV and HRTV. These results reveal low seroprevalence of important agricultural, wildlife, and zoonotic pathogens and underline the need for continued surveillance in this and other regions in the face of changing environmental conditions.

Reconstructing Mayaro virus circulation in French Guiana shows frequent spillovers.

Characterizing the circulation of Mayaro virus (MAYV), an emerging arbovirus threat, is essential for risk assessment but challenging due to cross-reactivity with other alphaviruses such as chikungunya virus (CHIKV). Here, we develop an analytical framework to jointly assess MAYV epidemiology and the extent of cross-reactivity with CHIKV from serological data collected throughout French Guiana (N = 2697). We find strong evidence of an important sylvatic cycle for MAYV with most infections occurring near the natural reservoir in rural areas and in individuals more likely to go to the forest (i.e., adult males) and with seroprevalences of up to 18% in some areas. These findings highlight the need to strengthen MAYV surveillance in the region and showcase how modeling can improve interpretation of cross-reacting assays.

Influence of herd immunity in the cyclical nature of arboviruses.

We review and contrast the evidence for an effect of amplifying host herd immunity on circulation and human exposure to arboviruses. Herd immunity of short-lived West Nile virus avian amplifying hosts appears to play a limited role in levels of enzootic circulation and spillover infections of humans, which are not amplifiers. In contrast, herd immunity of nonhuman primate hosts for enzootic Zika, dengue, and chikungunya viruses is much stronger and appears to regulate to a large extent the periodicity of sylvatic amplification in Africa. Following the recent Zika and chikungunya pandemics, human herd immunity in the Americas quickly rose to ∼50% in many regions, although seroprevalence remains patchy. Modeling from decades of chikungunya circulation in Asia suggests that this level of herd immunity will suppress for many years major chikungunya and Zika epidemics in the Americas, followed by smaller outbreaks as herd immunity cycles with a periodicity of up to several decades.

Pan-viral protection against arboviruses by activating skin macrophages at the inoculation site.

Arthropod-borne viruses (arboviruses) are important human pathogens for which there are no specific antiviral medicines. The abundance of genetically distinct arbovirus species, coupled with the unpredictable nature of their outbreaks, has made the development of virus-specific treatments challenging. Instead, we have defined and targeted a key aspect of the host innate immune response to virus at the arthropod bite that is common to all arbovirus infections, potentially circumventing the need for virus-specific therapies. Using mouse models and human skin explants, we identify innate immune responses by dermal macrophages in the skin as a key determinant of disease severity. Post-exposure treatment of the inoculation site by a topical TLR7 agonist suppressed both the local and subsequent systemic course of infection with a variety of arboviruses from the Alphavirus, Flavivirus, and Orthobunyavirus genera. Clinical outcome was improved in mice after infection with a model alphavirus. In the absence of treatment, antiviral interferon expression to virus in the skin was restricted to dermal dendritic cells. In contrast, stimulating the more populous skin-resident macrophages with a TLR7 agonist elicited protective responses in key cellular targets of virus that otherwise proficiently replicated virus. By defining and targeting a key aspect of the innate immune response to virus at the mosquito bite site, we have identified a putative new strategy for limiting disease after infection with a variety of genetically distinct arboviruses.

Analysis in a murine model points to IgG responses against the 34k2 salivary proteins from Aedes albopictus and Aedes aegypti as novel promising candidate markers of host exposure to Aedes mosquitoes.

BACKGROUND: Aedes mosquitoes are vectors of arboviral diseases of great relevance for public health. The recent outbreaks of dengue, Zika, chikungunya and the rapid worldwide spreading of Aedes albopictus emphasize the need for improvement of vector surveillance and control. Host antibody response to mosquito salivary antigens is emerging as a relevant additional tool to directly assess vector-host contact, monitor efficacy of control interventions and evaluate risk of arboviral transmission. METHODOLOGY/PRINCIPAL FINDINGS: Groups of four BALB/c mice were immunized by exposure to bites of either Aedes albopictus or Aedes aegypti. The 34k2 salivary proteins from Ae. albopictus (al34k2) and Ae. aegypti (ae34k2) were expressed in recombinant form and Ae. albopictus salivary peptides were designed through B-cell epitopes prediction software. IgG responses to salivary gland extracts, peptides, al34k2 and ae34k2 were measured in exposed mice. Both al34k2 and ae34k2, with some individual and antigen-specific variation, elicited a clearly detectable antibody response in immunized mice. Remarkably, the two orthologous proteins showed very low level of immune cross-reactivity, suggesting they may eventually be developed as species-specific markers of host exposure. The al34k2 immunogenicity and the limited immune cross-reactivity to ae34k2 were confirmed in a single human donor hyperimmune to Ae. albopictus saliva. CONCLUSIONS/SIGNIFICANCE: Our study shows that exposure to bites of Ae. albopictus or Ae. aegypti evokes in mice species-specific IgG responses to al34k2 or ae34k2, respectively. Deeper understanding of duration of antibody response and validation in natural conditions of human exposure to Aedes mosquitoes are certainly needed. However, our findings point to the al34k2 salivary protein as a promising potential candidate for the development of immunoassays to evaluate human exposure to Ae. albopictus. This would be a step forward in the establishment of a serological toolbox for the simultaneous assessment of human exposure to Aedes vectors and the pathogens they transmit.

Selected arboviral diseases imported to Poland - current state of knowledge and perspectives for research.

INTRODUCTION: Arthropod-borne viruses are important causes of human morbidity worldwide. However, the available literatur and the epidemiological data concerning the importation to Poland of globally emerging arboviral infections, such as DENV, CHIKV, WNV, or ZIKV, are scarce. Only few seroepidemiologic studies concerning WNV in animals or humans in Poland have been published. OBJECTIVE: The aim of this review paper is to summarize and present the current state of knowledge and the perspectives for research concerning the importation and the risk posed by the introduction to Poland of the four above-mentioned arboviral diseases. CURRENT STATE OF KNOWLEDGE: Climate change may facilitate the northward expansion of both the vectors for diseases previously unseen in Europe, as well as of the viruses themselves, resulting in autochthonous cases of diseases previously exclusively imported. Little is known about the importation of arboviral diseases to Poland because of the frequently asymptomatic or self-limiting course of the disease, lack of epidemiologic studies or effective disease reporting, as well as inadequate access to diagnostic methods. CONCLUSIONS: Further epidemiologic studies in Polish travellers are necessary in order to prevent importation or introduction of the above-mentioned viruses, and to act against potential problems related to blood transfusion or organ transplantation from infected donors.

Mosquito-Specific Viruses-Transmission and Interaction.

Mosquito-specific viruses (MSVs) are a subset of insect-specific viruses that are found to infect mosquitoes or mosquito derived cells. There has been an increase in discoveries of novel MSVs in recent years. This has expanded our understanding of viral diversity and evolution but has also sparked questions concerning the transmission of these viruses and interactions with their hosts and its microbiome. In fact, there is already evidence that MSVs interact with the immune system of their host. This is especially interesting, since mosquitoes can be infected with both MSVs and arthropod-borne (arbo) viruses of public health concern. In this review, we give an update on the different MSVs discovered so far and describe current data on their transmission and interaction with the mosquito immune system as well as the effect MSVs could have on an arboviruses-co-infection. Lastly, we discuss potential uses of these viruses, including vector and transmission control.

Arbovirus circulation among febrile patients at the greater Accra Regional Hospital, Ghana.

OBJECTIVE: Arboviruses, Dengue and Chikungunya have become major international public health concerns due to their epidemics and introduction in new areas. In Ghana, little is known is about Dengue and Chikungunya viruses though the country has been listed as part of the 34 countries in which the viruses are endemic. This has been attributed partly to the lack of diagnostic tools for these viruses in several health facilities and institutions across the country. The purpose of this study was to detect and characterize these viral pathogens among febrile patients in Accra Ghana. RESULTS: This hospital-based cross-sectional study enrolled 260 suspected Dengue and/or Chikungunya febrile patients who submitted their clinical specimens of serum. Out of the total number tested with both molecular and serological tools, Chikungunya and Dengue specific total antibodies were detected from 72 (27.69%) and 180 (69.23%) respectively. None of the participants tested positive for Dengue and Chikungunya by reverse transcription-polymerase chain reaction (RT-PCR) and with the Dengue-specific NS1 antigen strip kits. Our findings suggested that Dengue and Chikungunya viruses may be circulating but are being missed among febrile patients. Differential diagnosis work-up in febrile patients should be made to include Dengue and Chikungunya infections.

Control of Acute Arboviral Infection by Natural Killer Cells.

The recent explosive pandemic of chikungunya virus (CHIKV) followed by Zika (ZIKV) virus infections occurring throughout many countries represents the most unexpected arrival of arthropod-borne viral diseases in the past 20 years. Transmitted through the bite of Aedes mosquitoes, the clinical picture associated with these acute arbovirus infections, including Dengue (DENV), CHIKV and ZIKV, ranges from classical febrile illness to life-threatening disease. Whereas ZIKV and CHIKV-mediated infections have previously been recognized as relatively benign diseases, in contrast to Dengue fever, recent epidemic events have brought waves of increased morbidity and mortality leading to a serious public health problem. Although the host immune response plays a crucial role in controlling infections, it may also promote viral spread and immunopathology. Here, we review recent developments in our understanding of the immune response, with an emphasis on the early antiviral immune response mediated by natural killer cells and emphasize their Janus-faced effects in the control of arbovirus infection and pathogenesis. Improving our understanding knowledge on of the mechanisms that control viral infection is crucial in the current race against the globalization of arbovirus epidemics.

Emerging Mechanisms of Insulin-Mediated Antiviral Immunity in Drosophila melanogaster.

Arboviruses (arthropod-borne viruses), such as Zika (ZIKV), West Nile (WNV), and dengue (DENV) virus, include some of the most significant global health risks to human populations. The steady increase in the number of cases is of great concern due to the debilitating diseases associated with each viral infection. Because these viruses all depend on the mosquito as a vector for disease transmission, current research has focused on identifying immune mechanisms used by insects to effectively harbor these viruses and cause disease in humans and other animals. Drosophila melanogaster are a vital model to study arboviral infections and host responses as they are a genetically malleable model organism for experimentation that can complement analysis in the virus' natural vectors. D. melanogaster encode a number of distinct mechanisms of antiviral defense that are found in both mosquito and vertebrate animal systems, providing a viable model for study. These pathways include canonical antiviral modules such as RNA interference (RNAi), JAK/STAT signaling, and the induction of STING-mediated immune responses like autophagy. Insulin signaling plays a significant role in host-pathogen interactions. The exact mechanisms of insulin-mediated immune responses vary with each virus type, but nevertheless ultimately demonstrates that metabolic and immune signaling are coupled for antiviral immunity in an arthropod model. This mini review provides our current understanding of antiviral mechanisms in D. melanogaster, with a focus on insulin-mediated antiviral signaling, and how such immune responses pertain to disease models in vertebrate and mosquito species.