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Proper thyroid function is essential to the developing brain, including dopamine neuron differentiation, growth, and maintenance. Stress across the lifespan impacts thyroid hormone signaling and anxiety disorders and depression have been associated with thyroid dysfunction (both hypo- and hyper-active). However, less is known about how stress during postnatal development impacts thyroid function and related brain development. Our previous work in mice demonstrated that early-life stress (ELS) transiently impinged on expression of a transcription factor in dopamine neurons, Otx2 , shown to be regulated by thyroid hormones. We hypothesized that thyroid hormone signaling may link experience of ELS with transcriptional dysregulation within the dopaminergic midbrain, and ultimately behavior. Here, we find that ELS transiently increases thyroid-stimulating hormone levels (inversely related to thyroid signaling) in both male and female mice at P21, an effect which recovers by adolescence. We next tested whether transient treatment of ELS mice with synthetic thyroid hormone (levothyroxine, LT4) could ameliorate the impact of ELS on sensitivity to future stress, and on expression of genes related to dopamine neuron development and maintenance, thyroid signaling, and plasticity within the ventral tegmental area. Among male mice, but not females, juvenile LT4 treatment prevented hypersensitivity to adult stress. We also found that rescuing developmental deficits in thyroid hormone signaling after ELS restored levels of some genes altered directly by ELS, and prevented alterations in expression of other genes sensitive to the second hit of adult stress. These findings suggest that thyroid signaling mediates the deleterious impact of ELS on VTA development, and that temporary treatment of hypothyroidism after ELS may be sufficient to prevent future stress hypersensitivity. • Plasma TSH levels are increased in juvenile male and female mice after early life stress but recover by adolescence • Rescuing impaired thyroid by LT4 treatment after early life stress promotes behavioral resiliency to adult stress • LT4 treatment after early life stress restores or protects expression of dopamine- and thyroid-related genes in the VTA [ABSTRACT FROM AUTHOR]

Rodents have long been recognized as the principal reservoirs of hantaviruses. However, with the discovery of genetically distinct and phylogenetically divergent lineages of hantaviruses in multiple species of shrews, moles, and insectivorous bats from widely separated geographic regions, a far more complex landscape of hantavirus host distribution, evolution, and phylogeography is emerging. Detailed phylogenetic analyses, based on partial and full-length genomes of previously described rodent-borne hantaviruses and newly detected non-rodent-borne hantaviruses, indicate an Asian origin and support the emerging concept that ancestral non-rodent mammals may have served as the hosts of primordial hantaviruses. [ABSTRACT FROM AUTHOR]

Vector-borne diseases persist in transmission systems that usually comprise heterogeneously distributed vectors and hosts leading to a highly heterogeneous case distribution. In this study, we build on principles of classical mathematical epidemiology to investigate spatial heterogeneity of disease risk for vector-borne diseases. Land cover delineates habitat suitability for vectors, and land use determines the spatial distribution of humans. We focus on the risk of exposure for dengue transmission on the Hawaiian island of Oahu, where the vector Aedes albopictus is well established and areas of dense human population exist. In Hawai'i, dengue virus is generally absent, but occasionally flares up when introduced. It is therefore relevant to investigate risk, but difficult to do based on disease incidence data. Based on publicly available data (land cover, land use, census data, surveillance mosquito trapping), we map the spatial distribution of vectors and human hosts and finally overlay them to produce a vector-to-host ratio map. The resulting high-resolution maps indicate a high spatial variability in vector-to-host ratio suggesting that risk of exposure is spatially heterogeneous and varies according to land cover and land use. [ABSTRACT FROM AUTHOR]

Background: The discovery of genetically distinct hantaviruses in shrews (Order Soricomorpha, Family Soricidae) from widely separated geographic regions challenges the hypothesis that rodents (Order Rodentia, Family Muridae and Cricetidae) are the primordial reservoir hosts of hantaviruses and also predicts that other soricomorphs harbor hantaviruses. Recently, novel hantavirus genomes have been detected in moles of the Family Talpidae, including the Japanese shrew mole (Urotrichus talpoides) and American shrew mole (Neurotrichus gibbsii). We present new insights into the evolutionary history of hantaviruses gained from a highly divergent hantavirus, designated Nova virus (NVAV), identified in the European common mole (Talpa europaea) captured in Hungary. Methodology/Principal Findings: Pair-wise alignment and comparison of the full-length S- and L-genomic segments indicated moderately low sequence similarity of 54-65% and 46-63% at the nucleotide and amino acid levels, respectively, between NVAV and representative rodent- and soricid-borne hantaviruses. Despite the high degree of sequence divergence, the predicted secondary structure of the NVAV nucleocapsid protein exhibited the characteristic coiled-coil domains at the amino-terminal end, and the L-segment motifs, typically found in hantaviruses, were well conserved. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that NVAV formed a distinct clade that was evolutionarily distant from all other hantaviruses. Conclusions: Newly identified hantaviruses harbored by shrews and moles support long-standing virus-host relationships and suggest that ancestral soricomorphs, rather than rodents, may have been the early or original mammalian hosts. [ABSTRACT FROM AUTHOR]

Abstract: A genetically distinct hantavirus, designated Oxbow virus (OXBV), was detected in tissues of an American shrew mole (Neurotrichus gibbsii), captured in Gresham, Oregon, in September 2003. Pairwise analysis of full-length S- and M- and partial L-segment nucleotide and amino acid sequences of OXBV indicated low sequence similarity with rodent-borne hantaviruses. Phylogenetic analyses using maximum-likelihood and Bayesian methods, and host–parasite evolutionary comparisons, showed that OXBV and Asama virus, a hantavirus recently identified from the Japanese shrew mole (Urotrichus talpoides), were related to soricine shrew-borne hantaviruses from North America and Eurasia, respectively, suggesting parallel evolution associated with cross-species transmission. [Copyright &y& Elsevier]

We sequenced the envelope (E) genes of 59 DEN-2 isolates collected from ten Caribbean islands, six South American countries, and two Central American countries between 1981 and 2000, a period characterized by hyperendemicity and increased incidence of severe dengue. Fifty-two isolates belonged to “American/Asian” subtype IIIb, possessing a characteristic polar residue at envelope aa position 390 (N [n = 48] or S [n = 4]) common to that group. Six isolates from Trinidad (1981), Honduras (1991 [4]), and El Salvador (1987) fell into the “Native American” subtype V (D at aa 390), and one from Honduras (1986) belonged to “Asian” subtype I. The data suggest that after its first isolation in the Caribbean in 1981, genotype IIIb spread throughout the Americas and effectively replaced subtype V throughout the Caribbean basin. The strain also evolved into several distinct lineages, based on substitutions in the E glycoprotein (amino acids 91 and 131), two of which were still in circulation in 2000. Interestingly, a molecular clock did not fit the data well, suggesting that other sources of rate variation, such as differential selection or differences in effective population sizes, may exist among lineages. Our results indicate the importance of large temporal- and geographical-scale phylogenetic studies in understanding disease dynamics, particularly where replacements between regions can occur. [Copyright &y& Elsevier]

We sequenced the E gene and adjacent prM/M and NS1 junctions (1940 bp) of 48 Dengue-4 (DEN-4) isolates collected between 1981 and 1999 from 8 Caribbean islands and from 7 South and Central American countries. Phylogenetic analysis confirms a single introduction in the early 1980s and a high degree of gene flow resulting in a pattern of evolution defined more by time period than geographic origin, especially within the Caribbean basin. A modern Caribbean clade consisting of four distinct lineages has arisen, comprised of isolates from Caribbean islands and nearby regions of South America. This clade is defined by three amino acid substitutions in the E (aa 163 and 351) and NS1 (aa 52) proteins. These findings highlight the importance of migration and gene flow in dengue viral change and suggest that efforts to understand disease dynamics in the Caribbean basin need to focus at regional, rather than local scales. [Copyright &y& Elsevier]

Major dengue epidemics throughout Nicaragua's history have been dominated by 1 of 4 dengue virus serotypes (DENV-1-4). To examine serotypes during the dengue epidemic in Nicaragua in 2022, we performed real-time genomic surveillance in-country and documented cocirculation of all 4 serotypes. We observed a shift toward co-dominance of DENV-1 and DENV-4 over previously dominant DENV-2. By analyzing 135 new full-length DENV sequences, we found that introductions underlay the resurgence: DENV-1 clustered with viruses from Ecuador in 2014 rather than those previously seen in Nicaragua; DENV-3, which last circulated locally in 2014, grouped instead with Southeast Asia strains expanding into Florida and Cuba in 2022; and new DENV-4 strains clustered within a South America lineage spreading to Florida in 2022. In contrast, DENV-2 persisted from the formerly dominant Nicaragua clade. We posit that the resurgence emerged from travel after the COVID-19 pandemic and that the resultant intensifying hyperendemicity could affect future dengue immunity and severity. [ABSTRACT FROM AUTHOR]

Early-life stress (ELS) is one of the strongest lifetime risk factors for depression, anxiety, suicide, and other psychiatric disorders, particularly after facing additional stressful events later in life. Human and animal studies demonstrate that ELS sensitizes individuals to subsequent stress. However, the neurobiological basis of such stress sensitization remains largely unexplored. We hypothesized that ELS-induced stress sensitization would be detectable at the level of neuronal ensembles, such that cells activated by ELS would be more reactive to adult stress. To test this, we leveraged transgenic mice to genetically tag, track, and manipulate experience-activated neurons. We found that in both male and female mice, ELS-activated neurons within the nucleus accumbens (NAc), and to a lesser extent the medial prefrontal cortex, were preferentially reactivated by adult stress. To test whether reactivation of ELS-activated ensembles in the NAc contributes to stress hypersensitivity, we expressed hM4Dis receptor in control or ELS-activated neurons of pups and chemogenetically inhibited their activity during experience of adult stress. Inhibition of ELS-activated NAc neurons, but not control-tagged neurons, ameliorated social avoidance behavior following chronic social defeat stress in males. These data provide evidence that ELS-induced stress hypersensitivity is encoded at the level of corticolimbic neuronal ensembles. [ABSTRACT FROM AUTHOR]

Effective population size characterizes the genetic variability in a population and is a parameter of paramount importance in population genetics and evolutionary biology. Kingman's coalescent process enables inference of past population dynamics directly from molecular sequence data, and researchers have developed a number of flexible coalescent-based models for Bayesian nonparametric estimation of the effective population size as a function of time. Major goals of demographic reconstruction include identifying driving factors of effective population size, and understanding the association between the effective population size and such factors. Building upon Bayesian nonparametric coalescent-based approaches, we introduce a flexible framework that incorporates time-varying covariates that exploit Gaussian Markov random fields to achieve temporal smoothing of effective population size trajectories. To approximate the posterior distribution, we adapt efficient Markov chain Monte Carlo algorithms designed for highly structured Gaussian models. Incorporating covariates into the demographic inference framework enables the modeling of associations between the effective population size and covariates while accounting for uncertainty in population histories. Furthermore, it can lead to more precise estimates of population dynamics. We apply our model to four examples. We reconstruct the demographic history of raccoon rabies inNorth America and find a significant association with the spatiotemporal spread of the outbreak. Next, we examine the effective population size trajectory of the DENV-4 virus in Puerto Rico along with viral isolate count data and find similar cyclic patterns. We compare the population history of the HIV-1 CRF02_AG clade in Cameroon with HIV incidence and prevalence data and find that the effective population size is more reflective of incidence rate. Finally, we explore the hypothesis that the population dynamics of musk ox during the Late Quaternary period were related to climate change. [ABSTRACT FROM AUTHOR]

Abstract: Dengue is an expanding arboviral disease of variable severity characterized by the emergence of virus strains with greater fitness, epidemic potential and possibly virulence. To investigate the role of dengue virus (DENV) strain variation on epidemic activity we studied DENV-2 viruses from a series of South Pacific islands experiencing outbreaks of varying intensity and clinical severity. Initially appearing in 1971 in Tahiti and Fiji, the virus was responsible for subsequent epidemics in American Samoa, New Caledonia and Niue Island in 1972, reaching Tonga in 1973 where there was near-silent transmission for over a year. Based on whole-genome sequencing and phylogenetic analysis on 20 virus isolates, Tonga viruses were genetically unique, clustering in a single clade. Substitutions in the pre-membrane (prM) and nonstructural genes NS2A and NS4A correlated with the attenuation of the Tongan viruses and suggest that genetic change may play a significant role in dengue epidemic severity. [ABSTRACT FROM AUTHOR]

More than 20 years ago, hantaviral antigens were reported in tissues of the Eurasian common shrew (Sorex araneus), Eurasian water shrew (Neomys fodiens) and common mole (Talpa europea), suggesting that insectivores, or soricomorphs, might serve as reservoirs of unique hantaviruses. Using RT-PCR, sequences of a genetically distinct hantavirus, designated Seewis virus (SWSV), were amplified from lung tissue of a Eurasian common shrew, captured in October 2006 in Graubünden, Switzerland. Pair-wise analysis of the full-length S and partial M and L segments of SWSV indicated approximately 55%-72% similarity with hantaviruses harbored by Murinae, Arvicolinae, Neotominae and Sigmodontinae rodents. Phylogenetically, SWSV grouped with other recently identified shrew-borne hantaviruses. Intensified efforts are underway to clarify the genetic diversity of SWSV throughout the geographic range of the Eurasian common shrew, as well as to determine its relevance to human health. [ABSTRACT FROM AUTHOR]

Despite the critical role that contact between hosts and vectors, through vector bites, plays in driving vector-borne disease (VBD) transmission, transmission risk is primarily studied through the lens of vector density and overlooks host–vector contact dynamics. This review article synthesizes current knowledge of host–vector contact with an emphasis on mosquito bites. It provides a framework including biological and mathematical definitions of host–mosquito contact rate, blood-feeding rate, and per capita biting rates. We describe how contact rates vary and how this variation is influenced by mosquito and vertebrate factors. Our framework challenges a classic assumption that mosquitoes bite at a fixed rate determined by the duration of their gonotrophic cycle. We explore alternative ecological assumptions based on the functional response, blood index, forage ratio, and ideal free distribution within a mechanistic host–vector contact model. We highlight that host–vector contact is a critical parameter that integrates many factors driving disease transmission. A renewed focus on contact dynamics between hosts and vectors will contribute new insights into the mechanisms behind VBD spread and emergence that are sorely lacking. Given the framework for including contact rates as an explicit component of mathematical models of VBD, as well as different methods to study contact rates empirically to move the field forward, researchers should explicitly test contact rate models with empirical studies. Such integrative studies promise to enhance understanding of extrinsic and intrinsic factors affecting host–vector contact rates and thus are critical to understand both the mechanisms driving VBD emergence and guiding their prevention and control. [ABSTRACT FROM AUTHOR]

High-throughput nucleic acid sequencing has greatly accelerated the discovery of viruses in the environment. Mosquitoes, because of their public health importance, are among those organisms whose viromes are being intensively characterized. Despite the deluge of sequence information, our understanding of the major drivers influencing the ecology of mosquito viromes remains limited. Using methods to increase the relative proportion of microbial RNA coupled with RNA-seq we characterize RNA viruses and other symbionts of three mosquito species collected along a rural to urban habitat gradient in Thailand. The full factorial study design allows us to explicitly investigate the relative importance of host species and habitat in structuring viral communities. We found that the pattern of virus presence was defined primarily by host species rather than by geographic locations or habitats. Our result suggests that insect-associated viruses display relatively narrow host ranges but are capable of spreading through a mosquito population at the geographical scale of our study. We also detected various single-celled and multicellular microorganisms such as bacteria, alveolates, fungi, and nematodes. Our study emphasizes the importance of including ecological information in viromic studies in order to gain further insights into viral ecology in systems where host specificity is driving both viral ecology and evolution. [ABSTRACT FROM AUTHOR]

Little is known about the extent and serotypes of dengue viruses circulating in Africa. We evaluated the presence of dengue viremia during 4 years of surveillance (2014-2017) among children with febrile illness in Kenya. Acutely ill febrile children were recruited from 4 clinical sites in western and coastal Kenya, and 1,022 participant samples were tested by using a highly sensitive real-time reverse transcription PCR. A complete case analysis with genomic sequencing and phylogenetic analyses was conducted to characterize the presence of dengue viremia among participants during 2014-2017. Dengue viremia was detected in 41.9% (361/862) of outpatient children who had undifferentiated febrile illness in Kenya. Of children with confirmed dengue viremia, 51.5% (150/291) had malaria parasitemia. All 4 dengue virus serotypes were detected, and phylogenetic analyses showed several viruses from novel lineages. Our results suggests high levels of dengue virus infection among children with undifferentiated febrile illness in Kenya. [ABSTRACT FROM AUTHOR]

Vector-borne diseases are a major health burden, yet factors affecting their spread are only partially understood. For example, microbial symbionts can impact mosquito reproduction, survival, and vectorial capacity, and hence affect disease transmission. Nonetheless, current knowledge of mosquito-associated microbial communities is limited. To characterize the bacterial and eukaryotic microbial communities of multiple vector species collected from different habitat types in disease endemic areas, we employed next-generation 454 pyrosequencing of 16S and 18S rRNA amplicon libraries, also known as metabarcoding. We investigated pooled whole adult mosquitoes of three medically important vectors, Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus, collected from different habitats across central Thailand where we previously characterized mosquito diversity. Our results indicate that diversity within the mosquito microbiota is low, with the majority of microbes assigned to one or a few taxa. Two of the most common eukaryotic and bacterial genera recovered (Ascogregarina and Wolbachia, respectively) are known mosquito endosymbionts with potentially parasitic and long evolutionary relationships with their hosts. Patterns of microbial composition and diversity appeared to differ by both vector species and habitat for a given species, although high variability between samples suggests a strong stochastic element to microbiota assembly. In general, our findings suggest that multiple factors, such as habitat condition and mosquito species identity, may influence overall microbial community composition, and thus provide a basis for further investigations into the interactions between vectors, their microbial communities, and human-impacted landscapes that may ultimately affect vector-borne disease risk. [ABSTRACT FROM AUTHOR]

Dengue has emerged globally as a major human health problem since the 1950s and is now the most important arboviral disease of humans, infecting nearly 400 million people annually. While some cases are asymptomatic, others can develop a febrile illness (dengue fever) or even progress to severe and fatal dengue. Dengue is caused by any of 4 closely related but distinct viruses, known as Dengue virus serotype 1 to 4 (DENV-1 to DENV-4) which are maintained in endemic transmission to humans in large urban centers of the tropics by Aedes mosquitoes. Since the early 1960s, Puerto Rico, a major metropolitan center in the Caribbean, has experienced increasingly larger and clinically more severe epidemics following the introduction of all four dengue serotypes. The first dengue hemorrhagic fever epidemic in 1986, and a particularly severe outbreak in 1998 were dominated by novel DENV-4 strains that evolved in Puerto Rico, replacing earlier strains and spreading throughout the region. Sequence characterization of 54 complete DENV-4 genomes and their comparative evolution against 74 previously published viral sequences from the region over several decades shows that DENV-4 strains from these periods were genetically distinct based on unique changes in the envelope and non-structural genes. Their replacement of earlier strains in Puerto Rico progressed rapidly, suggesting that strong natural selection played a role in their fixation. This study confirms that DENVs evolve through rapid lineage turnover driven in part by natural selection and genetic drift. [ABSTRACT FROM AUTHOR]

Arthropod-borne viruses significantly impact human health. They span multiple families, all of which include viruses not known to cause disease. Characterizing these representatives could provide insights into the origins of their disease-causing counterparts. Field-caught Aedes aegypti mosquitoes from Nakhon Nayok, Thailand, underwent metagenomic shotgun sequencing to reveal a Bunyavirus closely related to Phasi Charoen (PhaV) virus, isolated in 2009 from Ae. aegypti near Bangkok. Phylogenetic analysis of this virus suggests it is basal to the Phlebovirus genus thus making it ideally positioned phylogenetically for understanding the evolution of these clinically important viruses. Genomic analysis finds that a gene necessary for virulence in vertebrates, but not essential for viral replication in arthropods, is missing. The sequencing of this phylogenetically-notable and genomically-unique Phlebovirus from wild mosquitoes exemplifies the utility and efficacy of metagenomic shotgun sequencing for virus characterization in arthropod vectors of human diseases. [ABSTRACT FROM AUTHOR]

From November 2008-May 2009 Cairns Queensland Australia was struck by an explosive epidemic of DENV-3 that exceeded the capacity of highly skilled dengue control team to control it. We describe the environmental, virological and entomological factors associated with this outbreak to better understand the circumstances leading to its occurrence. Patient interviews, serological results and viral sequencing strongly suggest that the imported index case was infected in Kalimantan, Indonesia. A delay in notification of 27 days from importation of the index case until Queensland Health was notified of dengue transmission allowed the virus to amplify and spread unchecked through November 2008. Unseasonably warm weather, with daily mean temperatures exceeding 30°C, occurred in late November and would have shortened the extrinsic incubation period of the virus and enhanced transmission. Analysis of case movements early in the outbreak indicated that the total incubation period was as low as 9–11 days. This was supported by laboratory vector competence studies that found transmission by Aedes aegypti occurred within 5 days post exposure at 28°C. Effective vector competence rates calculated from these transmission studies indicate that early transmission contributed to the explosive dengue transmission observed in this outbreak. Collections from BG sentinel traps and double sticky ovitraps showed that large populations of the vector Ae. aegypti occurred in the transmission areas from November – December 2008. Finally, the seasonal movement of people around the Christmas holiday season enhanced the spread of DENV-3. These results suggest that a strain of DENV-3 with an unusually rapid transmission cycle was able to outpace vector control efforts, especially those reliant upon delayed action control such as lethal ovitraps. [ABSTRACT FROM AUTHOR]

Abstract: Spurred by the recent isolation of a novel hantavirus, named Imjin virus (MJNV), from the Ussuri white-toothed shrew (Crocidura lasiura), targeted trapping was conducted for the phylogenetically related Asian lesser white-toothed shrew (Crocidura shantungensis). Pair-wise alignment and comparison of the S, M and L segments of a newfound hantavirus, designated Jeju virus (JJUV), indicated remarkably low nucleotide and amino acid sequence similarity with MJNV. Phylogenetic analyses, using maximum likelihood and Bayesian methods, showed divergent ancestral lineages for JJUV and MJNV, despite the close phylogenetic relationship of their reservoir soricid hosts. Also, no evidence of host switching was apparent in tanglegrams, generated by TreeMap 2.0β. [Copyright &y& Elsevier]

Until recently, the single known exception to the rodent-hantavirus association was Thottapalayam virus (TPMV), a long-unclassified virus isolated from the Asian house shrew (Suncus murinus). Robust gene amplification techniques have now uncovered several genetically distinct hantaviruses from shrews in widely separated geographic regions. Here, we report the characterization of a newly identified hantavirus, designated Imjin virus (MJNV), isolated from the lung tissues of Ussuri white-toothed shrews of the species Crocidura lasiura (order Soricomorpha, family Soricidae, subfamily Crocidurinae) captured near the demilitarized zone in the Republic of Korea during 2004 and 2005. Seasonal trapping revealed the highest prevalence of MJNV infection during the autumn, with evidence of infected shrews' clustering in distinct foci. Also, marked male predominance among anti-MJNV immunoglobulin G antibody-positive Ussuri shrews was found, whereas the male-to-female ratio among seronegative Ussuri shrews was near 1. Plaque reduction neutralization tests showed no cross neutralization for MJNV and rodent-borne hantaviruses but one-way cross neutralization for MJNV and TPMV. The nucleotide and deduced amino acid sequences for the different MJNV genomic segments revealed nearly the same calculated distances from hantaviruses harbored by rodents in the subfamilies Murinae, Arvicolinae, Neotominae, and Sigmodontinae. Phylogenetic analyses of full-length S, M, and L segment sequences demonstrated that MJNV shared a common ancestry with TPMV and remained in a distinct out-group, suggesting early evolutionary divergence. Studies are in progress to determine if MJNV is pathogenic for humans. [ABSTRACT FROM AUTHOR]

Sequence analysis of the full-length medium segment and the partial small and large segments of a hantavirus, detected by reverse transcription-PCR in lung tissues of the Chinese mole shrew (Anourosorex squamipes) captured in Cao Bang Province, Vietnam, in December 2006, indicated that it is genetically distinct from rodentborne hantaviruses. [ABSTRACT FROM AUTHOR]

Phylogenetic analyses, based on partial medium- and large-segment sequences, support an ancient evolutionary origin of a genetically distinct hantavirus detected by reverse transcription-PCR in tissues of northern short-tailed shrews (Blarina brevicauda) captured in Minnesota in August 1998. To our knowledge, this is the first evidence of hantaviruses harbored by shrews in the Americas. [ABSTRACT FROM AUTHOR]

Dengue virus type 4 (DENV-4) was first reported in the Americas in 1981, where it caused epidemics of dengue fever Throughout the region. In the same year, the region's first epidemic of dengue hemorrhagic lever was reported, caused by an Asian strain of dengue virus type 2 (DENV-2) that was distinct from the American subtype circulating previously. Despite the importance of these epidemics, little is known about the rates or determinants of viral spread among island and mainland populations or their directions of movement. We employed a Bayesian coalescent approach to investigate the transmission histories of DENV-2 and DENV-4 since their introduction in 1981 and a parsimony method to assess patterns of strain migration. For both viruses there was an initial invasion phase characterized by an exponential increase in the number of DENV lineages, after which levels of genetic diversity remained constant despite reported fluctuations in DENV-2 and DENV-4 activity. Strikingly, viral lineage numbers increased far more rapidly for DENV-4 than DENV-2, indicative of a more rapid rate of exponential population growth in DENV-4 or a higher rate of geographic dispersal, allowing this virus to move more effectively among localities. We propose that these contrasting dynamics may reflect underlying differences in patterns of host immunity. Despite continued gene flow along particular transmission routes, the overall extent of viral traffic was less than expected under panmixis. Hence, DENV in the Americas has a clear geographic structure that maintains viral diversity between outbreaks. [ABSTRACT FROM AUTHOR]

Arthropod-borne viruses (arboviruses) comprise a significant and ongoing threat to human health, infecting hundreds of millions annually. Three such arboviruses include circumtropical dengue, Zika, and chikungunya viruses, exhibiting continuous emergence primarily via Aedes mosquito vectors. Nicaragua has experienced endemic dengue virus (DENV) transmission involving multiple serotypes since 1985, with chikungunya virus (CHIKV) reported in 2014–2015, followed by Zika virus (ZIKV) first reported in 2016. In order to identify patterns of genetic variation and selection pressures shaping the evolution of co-circulating DENV serotypes in light of the arrival of CHIKV and ZIKV, we employed whole-genome sequencing on an Illumina MiSeq platform of random-amplified total RNA libraries to characterize 42 DENV low-passage isolates, derived from viremic patients in Nicaragua between 2013 and 2016. Our approach also revealed clinically undetected co-infections with CHIKV. Of the three DENV serotypes (1, 2, and 3) co-circulating during our study, we uncovered distinct patterns of evolution using comparative phylogenetic inference. DENV-1 genetic variation was structured into two distinct co-circulating lineages with no evidence of positive selection in the origins of either lineage, suggesting they are equally fit. In contrast, the evolutionary history of DENV-2 was marked by positive selection, and a unique, divergent lineage correlated with high epidemic potential emerged in 2015 to drive an outbreak in 2016. DENV-3 genetic variation remained unstructured into lineages throughout the period of study. Thus, this study reveals insights into evolutionary and epidemiologic trends exhibited during the circulation of multiple arboviruses in Nicaragua. • 42 dengue virus (DENV) isolates serotype 1-3 from viremic Nicaraguan patients (2013-2016) were sequenced and analyzed. • Three clinically undetected co-infections with chikungunya virus (CHIKV) were confirmed with high genome coverage. • DENV-1 isolates structured into two lineages with no evidence of positive selection suggesting they are equally fit. • DENV-2 evolution was marked by positive selection with a divergent lineage of high epidemic potential emerged in 2015. • DENV-3 isolates remained unstructured into lineages throughout the period of study. No evidence of positive selection. [ABSTRACT FROM AUTHOR]

We report West Nile virus (WNV) RNA in urine collected from a patient with encephalitis 8 days after symptom onset. Viral RNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR). Sequence and phylogenetic analysis confirmed the PCR product to have > or = 99% similarity to the WNV strain NY 2000-crow3356. [ABSTRACT FROM AUTHOR]