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A large national outbreak of chikungunya virus (CHIKV) was recently reported in Thailand. While dengue virus (DENV) infection tends to occur year-round with an upsurge in the rainy season, Zika virus (ZIKV) also circulates in the country. The overlap in the distribution of these viruses increased the probability of co-infections during the heightened CHIKV activity. By examining 1806 patient serum samples submitted for CHIKV diagnostics from October 2018-February 2020 (511 CHIKV-negatives and 1295 CHIKV-positives), we used real-time reverse transcription-polymerase chain reaction to identify DENV and ZIKV individually. A total of 29 ZIKV and 36 DENV single-infections were identified. Interestingly, 13 co-infection cases were observed, of which 8 were CHIKV/DENV, 3 were CHIKV/ZIKV, and 2 were DENV/ZIKV. There were six DENV genotypes (13 DENV-1 genotype I, 10 DENV-2 Asian I, 10 DENV-2 Cosmopolitan, 6 DENV-3 genotype I, 2 DENV-3 genotype III, and 5 DENV-4 genotype I). Additionally, ZIKV strains identified in this study either clustered with strains previously circulating in Thailand and Singapore, or with strains previously reported in China, French Polynesia, and the Americas. Our findings reveal the co-infection and genetic diversity patterns of mosquito-borne viruses circulating in Thailand. [ABSTRACT FROM AUTHOR]

Rift Valley fever (RVF) is an arboviral disease of humans and livestock responsible for severe economic and human health impacts. In humans, RVF spans a variety of clinical manifestations, ranging from an acute flu-like illness to severe forms of disease, including late-onset encephalitis. The large variations in human RVF disease are inadequately represented by current murine models, which overwhelmingly die of early-onset hepatitis. Existing mouse models of RVF encephalitis are either immunosuppressed, display an inconsistent phenotype, or develop encephalitis only when challenged via intranasal or aerosol exposure. In this study, the genetically defined recombinant inbred mouse resource known as the Collaborative Cross (CC) was used to identify mice with additional RVF disease phenotypes when challenged via a peripheral foot-pad route to mimic mosquito-bite exposure. Wild-type Rift Valley fever virus (RVFV) challenge of 20 CC strains revealed three distinct disease phenotypes: early-onset hepatitis, mixed phenotype, and late-onset encephalitis. Strain CC057/Unc, with the most divergent phenotype, which died of late-onset encephalitis at a median of 11 days post-infection, is the first mouse strain to develop consistent encephalitis following peripheral challenge. CC057/Unc mice were directly compared to C57BL/6 mice, which uniformly succumb to hepatitis within 2–4 days of infection. Encephalitic disease in CC057/Unc mice was characterized by high viral RNA loads in brain tissue, accompanied by clearance of viral RNA from the periphery, low ALT levels, lymphopenia, and neutrophilia. In contrast, C57BL/6 mice succumbed from hepatitis at 3 days post-infection with high viral RNA loads in the liver, viremia, high ALT levels, lymphopenia, and thrombocytopenia. The identification of a strain of CC mice as an RVFV encephalitis model will allow for future investigation into the pathogenesis and treatment of RVF encephalitic disease and indicates that genetic background makes a major contribution to RVF disease variation. Author summary: Rift Valley fever virus (RVFV) is a negative sense RNA arbovirus of clinical relevance found throughout Africa and into the Middle East. In humans, RVF disease exhibits various clinical manifestations including acute febrile illness, hepatitis, hemorrhagic fever, and encephalitis. Unfortunately, existing murine models have been limited to studies of acute lethal hepatitis. Here, we identify a mouse model in which all animals survive acute hepatitis and go on to succumb to late onset encephalitis. A key feature of this new experimental system is administration of the virus in the footpad (to mimic mosquito bite), to model a natural route of infection. Importantly in this work, we used the Collaborative Cross recombinant inbred mouse resource to identify this RVFV CNS model. Therefore, our study demonstrates that host genetics can modulate RVF disease manifestations. The identification of this model also enables the field for high throughput, in vivo studies of central nervous system pathogenesis as well as in vivo evaluation of vaccines and therapeutics targeted against RVF encephalitis. [ABSTRACT FROM AUTHOR]

Thogotoviruses are tick-borne arboviruses that comprise a unique genus within the Orthomyxoviridae family. Infections with thogotoviruses primarily cause disease in livestock with occasional reports of human infections suggesting a zoonotic potential. In the past, multiple genetically distinct thogotoviruses were isolated mostly from collected ticks. However, many aspects regarding their phylogenetic relationships, morphological characteristics, and virulence in mammals remain unclear. For the present comparative study, we used a collection of 10 different thogotovirus isolates from different geographic areas. Next-generation sequencing and subsequent phylogenetic analyses revealed a distinct separation of these viruses into two major clades, the Thogoto-like and Dhori-like viruses. Electron microscopy demonstrated a heterogeneous morphology with spherical and filamentous particles being present in virus preparations. To study their pathogenicity, we analyzed the viruses in a small animal model system. In intraperitoneally infected C57BL/6 mice, all isolates showed a tropism for liver, lung, and spleen. Importantly, we did not observe horizontal transmission to uninfected, highly susceptible contact mice. The isolates enormously differed in their capacity to induce disease, ranging from subclinical to fatal outcomes. In vivo multistep passaging experiments of two low-pathogenic isolates showed no increased virulence and sequence analyses of the passaged viruses indicated a high stability of the viral genomes after 10 mouse passages. In summary, our analysis demonstrates the broad genetic and phenotypic variability within the thogotovirus genus. Moreover, thogotoviruses are well adapted to mammals but their horizontal transmission seems to depend on ticks as their vectors. IMPORTANCE Since their discovery over 60 years ago, 15 genetically distinct members of the thogotovirus genus have been isolated. These arboviruses belong to the Orthomyxovirus family and share many features with influenza viruses. However, numerous of these isolates have not been characterized in depth. In the present study, we comparatively analyzed a collection of 10 different thogotovirus isolates to answer basic questions about their phylogenetic relationships, morphology, and pathogenicity in mice. Our results highlight shared and unique characteristics of this diverse genus. Taken together, these observations provide a framework for the phylogenic classification and phenotypic characterization of newly identified thogotovirus isolates that could potentially cause severe human infections as exemplified by the recently reported, fatal Bourbon virus cases in the United States. [ABSTRACT FROM AUTHOR]

In this review we examine how exploiting the Wolbachia –mosquito relationship has become an increasingly popular strategy for controlling arbovirus transmission. Field deployments of Wolbachia -infected mosquitoes have led to significant decreases in dengue virus incidence via high levels of mosquito population suppression and replacement, emphasizing the success of Wolbachia approaches. Here, we examine how improved knowledge of Wolbachia –host interactions has provided key insight into the mechanisms of the essential phenotypes of pathogen blocking and cytoplasmic incompatibility. And we discuss recent studies demonstrating that extrinsic factors, such as ambient temperature, can modulate Wolbachia density and maternal transmission. Finally, we assess the prospects of using Wolbachia to control other vectors and agricultural pest species. Wolbachia population suppression interventions reduce mosquito population size by 78–95%. Population replacement interventions can lead to establishment of Wolbachia in wild mosquitoes and significantly reduce dengue incidence. Extrinsic factors, including temperature, which can reduce Wolbachia density and impact the Wolbachia –host relationship, could be impacting intervention efficacy. Identification of the genetic basis of cytoplasmic incompatibility provides a platform to improve understanding of the phenotype in transinfected mosquitoes, including genetic variation and moderating factors. Pathogen blocking is an essential part of population replacement interventions, but still has no clear mechanism and is subject to potential weakening through a changing host–symbiont relationship or viral resistance. The use of Wolbachia to control agricultural pests is gathering momentum. [ABSTRACT FROM AUTHOR]

Dengue fever is a clinical manifestation of dengue virus (DENV) infection well defined by the intense host immune response with the development of high fever, anorexia, headache and muscle pain. Several immune mediators are involved in the pathophysiology of DENV infection, in which polymorphisms in immune molecule genes contribute with the susceptibility and severity of the infection. Several meta-analyses are available with significant findings in the association between genetic variants in immune-mediator genes and dengue, though the results may be false positive. Hence, to solve this issue, we have performed a systematic revaluation with Bayesian approaches to verify the false positive rate in these results. A systematic search was performed for meta-analytic studies on the aforementioned issue. The calculations of false positive report probability (FPRP) and the Bayesian false-discovery probability (BFDP) at the prior probability of 10-3 and 10-6 have been performed. To verify the methodological quality of the studies included, the evaluation by the Venice criteria was applied. In addition, gene-gene and protein-protein networks were designed. As results, seven meta-analyses on genetic variants in several immune-inflammatory mediator genes and DENV infection comprise the results. Only the polymorphisms in the TNF , MICB , PLCE1 , VDR , CD32 and HLA-A genes were considered as noteworthy. There was a heterogeneity profile for the results on Venice criteria indicating variability in the methodological quality. The gene-gene and protein-protein networks showed these immune mediators as relevant players in the disease. We suggest these polymorphisms as potential biomarkers for the pathogenesis and immune response against DENV. [ABSTRACT FROM AUTHOR]