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Background. Each year dengue virus (DENV) infects 400 million human but causes symptomatic disease in only a subset of patients, suggesting that host genetic factors may play a role. HLA molecules that restrict T-cell responses are one of the most polymorphic host factors in humans. Methods. Here we map HLA DRB1-restricted DENV-specific epitopes in individuals previously exposed to DENV, to identify the breadth and specificity of CD4 super(+) T-cell responses. To investigate whether HLA-specific variations in the magnitude of response might predict associations between dengue outcomes and HLA-DRB1 alleles, we assembled samples from hospitalized patients with known severity of disease. Results. The capsid protein followed by nonstructural protein 3 (NS3), NS2A, and NS5 were the most targeted proteins. We further noticed a wide variation in magnitude of T-cell responses as a function of the restricting DRB1 allele and found several HLA alleles that showed trends toward a lower risk of hospitalized disease were associated with a higher magnitude of T-cell responses. Conclusions. Comprehensive identification of unique CD4 super(+) T-cell epitopes across the 4 DENV serotypes allows the testing of T-cell responses by use of a simple, approachable technique and points to important implications for vaccine design.

We are developing a live-attenuated tetravalent dengue vaccine (TDV) candidate based on an attenuated dengue 2 virus (TDV-2) and 3 chimeric viruses containing the premembrane and envelope genes of dengue viruses (DENVs) -1, -3, and -4 expressed in the context of the attenuated TDV-2 genome (TDV-1, TDV-3, and TDV-4, respectively). In this study, we analyzed and characterized the CD8 super(+) T-cell response in flavivirus-naive human volunteers vaccinated with 2 doses of TDV 90 days apart via the subcutaneous or intradermal routes. Using peptide arrays and intracellular cytokine staining, we demonstrated that TDV elicits CD8 super(+) T cells targeting the nonstructural NS1, NS3, and NS5 proteins of TDV-2. The cells were characterized by the production of interferon-[gamma], tumor necrosis factor-[alpha], and to a lesser extent interleukin-2. Responses were highest on day 90 after the first dose and were still detectable on 180 days after the second dose. In addition, CD8+ T cells were multifunctional, producing > or =2 cytokines simultaneously, and cross-reactive to NS proteins of the other 3 DENV serotypes. Overall, these findings describe the capacity of our candidate dengue vaccine to elicit cellular immune responses and support the further evaluation of T-cell responses in samples from future TDV clinical trials.

In recent decades, many new flavi-like viruses have been discovered predominantly in different invertebrates and, as was recently shown, some of them may cause disease in humans. The Jingmenvirus (JMV) group holds a special place among flaviviruses and flavi-like viruses because they have a segmented ssRNA(+) genome. We detected Alongshan virus (ALSV), which is a representative of the JMV group, in ten pools of adult Ixodes persulcatus ticks collected in two geographically-separated Russian regions. Three of the ten strains were isolated in the tick cell line IRE/CTVM19. One of the strains persisted in the IRE/CTVM19 cells without cytopathic effect for three years. Most ALSV virions purified from tick cells were spherical with a diameter of approximately 40.5 nm. In addition, we found smaller particles of approximately 13.1 nm in diameter. We obtained full genome sequences of all four segments of two of the isolated ALSV strains, and partial sequences of one segment from the third strain. Phylogenetic analysis on genome segment 2 of the JMV group clustered our novel strains with other ALSV strains. We found evidence for the existence of a novel upstream open reading frame in the glycoprotein-coding segment of ALSV and other members of the JMV group.

Flaviviridae-caused diseases are a critical, emerging public health problem worldwide. Flaviviridae infections usually cause severe, acute or chronic diseases, such as liver damage and liver cancer resulting from a hepatitis C virus (HCV) infection and high fever and shock caused by yellow fever. Many researchers worldwide are investigating the mechanisms by which Flaviviridae cause severe diseases. Flaviviridae can interfere with the host’s innate immunity to achieve their purpose of proliferation. For instance, dengue virus (DENV) NS2A, NS2B3, NS4A, NS4B and NS5; HCV NS2, NS3, NS3/4A, NS4B and NS5A; and West Nile virus (WNV) NS1 and NS4B proteins are involved in immune evasion. This review discusses the interplay between viral non-structural Flaviviridae proteins and relevant host proteins, which leads to the suppression of the host’s innate antiviral immunity.

Bussuquara virus (BSQV) was first discovered in the Brazilian Amazon in 1956. It is an arthropod-borne virus (arbovirus) in the genus Orthoflavivirus, family Flaviviridae. Since its discovery, BSQV has been sporadically detected across the South (Brazil, Columbia, and Argentina) and Central (Panama and Mexico) America and the Caribbean (Grenada), but there is minimal BSQV surveillance due to limited public health awareness and a lack of specific or sensitive diagnostics. BSQV exposure has been reported in a wide range of host and vector species, including humans. Little information is available in the literature and herein we summarize the published historical findings on BSQV and suggest a pathway for future studies to better understand its potential emergence into human populations.

This is the only confirmed case of St Louis Encephalitis reported in the UK in 2011. The St Louis virus is a member of the single stranded RNA Flaviviridae family and is transmitted to humans by mosquitoes, with birds acting as the amplifying host. The viraemia terminates approximately 1 week after the initial infection with subsequent neuronal damage being mediated immunologically. Incidence in the UK is extremely rare and approximately 10 cases occur every year in the USA where it is endemic. A 77-year-old man presented to 1 week after returning from a 7 week stay in Jamaica, with collapse, confusion and ataxia. Half way through his stay in Jamaica his relatives noticed that he had developed slurred speech, drowsiness and double incontinence. His mobility and power had gradually declined leading to recurrent falls. On admission he was apyrexial, haemodynamically stable, confused with systemic examination unremarkable. Nervous system exam demonstrated pyramidal weakness in both upper limbs but normal power and reflexes in his lower limbs. On day 4 of his admission he developed complex partial status confirmed on EEG which was successfully treated with anticonvulsants and acyclovir. Following this he remained in a persistently drowsy but rousable state. Investigations revealed a rising titre of the St Louis virus IgG in the serum on serial testing and IgG antibodies in the CSF, confirming the diagnosis. In patients with encephalitis who have recently returned from the Americas, infection by the St Louis virus should always be considered.

A group of patients with a febrile illness and a history of tick bites was identified in northeastern China. A previously unknown virus was determined to be a possible etiologic agent. This virus was also found in ticks in the area.

Background Alongshan virus (ALSV) is a novel discovered segmented flavivirus associated with human febrile illness in northeastern China. Ixodes persulcatus is considered as a candidate vector of ALSV in the endemic regions. However, the role of domesticated animals in the circulation and transmission of ALSV have not been investigated. To evaluate the prevalence of ALSV infections in domesticated animals, viral RNA and viral specific antibodies were detected in sheep and cattle in Hulunbuir of northeastern Inner Mongolia. The findings contribute to the understanding of the ecology and transmission of ALSV among different natural hosts. Methods A total of 480 animal serum samples were collected in Hulunbuir of northeastern China in May, 2017. Viral specific antibodies were tested by indirect enzyme-linked immunosorbent assay (ELISA) with a purified E. coli recombinant capsid protein (VP2) of ALSV (strain H3) and further detected by viral neutralization test (VNT). RNA in serum samples were extracted and detected for ALSV sequence by quantitative real-time RT-PCR. ALSV RNA positive samples were used for virus isolation. Results ALSV-specific antibodies were detected in 9.2% (22/240) of examined sheep and 4.6% (11/240) of examined cattle by ELISA, while lower serological positivity with 4.2% (10/240) for sheep and 1.7% (4/240) for cattle was confirmed by VNT. In contrast, the prevalence of ALSV RNA was much higher, ranging from 26.3% (63/240) in sheep to 27.5% (66/240) in cattle. The partial S1 (NS5-like) and S3 (NS3-like) segments of ALSVs in sheep and cattle shared high identities of more than 98% to the human and tick isolates in the studied regions. Conclusions These results suggest that the natural infection of ALSV can be found in sheep and cattle in the endemic regions.

The emergence and spread of novel viral pathogens is a major threat to human health, particularly in the context of climate and human-induced change in land use. Alongshan virus (ALSV) is a tick-borne virus associated with human disease, which was first identified in northeast China. More recently, several studies reported the emergence of ALSV in mammalian and arthropod hosts in multiple different countries outside of Asia, and the first viral genome sequencing data has become available. ALSV is a member of the Jingmenvirus group closely related to the family. Unusually, the positive-sense, single-stranded RNA genome of ALSV is segmented and consists of four distinct segments, two of which show homology with the NS3 and NS5 protein encoding regions of non-segmented flaviviruses. Transmission of arthropod-borne pathogens will likely increase in the future due to environmental change mediated by a variety of environmental and ecological factors and increasing human encroachment into wild animal habitats. In this review, we present current knowledge of global ALSV distribution and emergence patterns, highlight genetic diversity, evolution and susceptible species. Finally, we discuss the role of this emerging tick-borne virus in the context of urbanization and global health.

Equestrian sports play a significant economic role in the horse industry. In recent years, numerous equine viruses have emerged, among which are equine Pegiviruses and the re-emerging Equine coronavirus (ECoV). These viruses are distributed globally and primarily cause subclinical infections with unknown morbidity, even if ECoV can occasionally induce febrile and diarrheic episodes. To broaden the data on the Italian equine population, a study was conducted to assess their prevalence in two distinct horse populations belonging to the Carabinieri Corps (CC) and the Italian Army (IA) of the Italian Armed Forces (IAF). Samples consisted of blood serum and rectal swabs of 436 horses collected within the national surveillance program for equine infectious anemia and gastrointestinal parasite monitoring and analyzed for Pegivirus (caballi and equi) and ECoV by Real-Time RT PCR. The prevalence detected were 6.56% and 3.53%, respectively, for Pegivirus caballi and equi for the IA, while for the CC, they were 10.13% and 0.84%. Only one sample tested positive for ECoV belonging to a horse of the CC. Phylogenetic analyses were carried out on the PCR-positive samples that were sequenced using Sanger protocols. Understanding the epidemiology of these viruses is essential for evaluating the implementation of effective prevention strategies.