Introduction and Spread of Dengue Virus 3, Florida, USA, May 2022-April 2023.

During May 2022-April 2023, dengue virus serotype 3 was identified among 601 travel-associated and 61 locally acquired dengue cases in Florida, USA. All 203 sequenced genomes belonged to the same genotype III lineage and revealed potential transmission chains in which most locally acquired cases occurred shortly after introduction, with little sustained transmission.

Intra-serotypic antigenic diversity of dengue virus serotype 3 in Thailand during 2004-2015.

In addition to the well-known differences among the four dengue serotypes, intra-serotypic antigenic diversity has been proposed to play a role in viral evolution and epidemic fluctuation. A replacement of genotype II by genotype III of dengue virus serotype 3 (DENV3) occurred in Thailand during 2007-2014, raising questions about the role of intra-serotypic antigenic differences in this genotype shift. We characterized the antigenic difference of DENV3 of genotypes II and III in Thailand, utilizing a neutralizing antibody assay with DENV3 vaccine sera and monotypic DENV3 sera. Although there was significant antigenic diversity among the DENV3, it did not clearly associate with the genotype. Our data therefore do not support the role of intra-serotypic antigenic difference in the genotype replacement. Amino acid alignment showed that eight positions are potentially associated with diversity between distinct antigenic subgroups. Most of these amino acids were found in envelope domain II. Some positions (aa81, aa124, and aa172) were located on the surface of virus particles, probably involving the neutralization sensitivity. Notably, the strains of both genotypes II and III showed clear antigenic differences from the vaccine genotype I strain. Whether this differencewill affect vaccine efficacy requires further studies.

Genetic characterization of dengue virus from patients presenting multi-serotypic infections in the Northern West Bengal, India.

Northern West Bengal, popularly known as North Bengal, is a dengue-endemic area, which has been severely affected by Dengue in the past few years resulting in massive hospitalizations and deaths. Genetic characterization of the circulating endemic dengue virus (DENV) serotypes is of paramount importance for the epidemiological understanding of the infection and subsequent vaccine development. The present study was conceived to characterize circulating dengue serotypes and to undertake phylogenetic study. EDTA blood samples of all (N = 83) NS1-positive cases of patients with acute febrile illness referred to different health care facilities were collected and processed for RNA isolation followed by the complementary DNA (cDNA) preparation. Serotype determination of dengue infection was done using conventional PCR by targeting the viral C-prM region. Phylogenetic tree was constructed by implementing the Maximum likelihood method. Out of 83 blood samples 17 were detected to be positive for the presence of dengue viral RNA. DENV3 was found to be the predominant serotype in the single-infection cases; however, we have detected multi-serotypic co-infections throughout the study. Joint pain was found to be the most valuable symptom for the prognosis of dengue. Sequence analyses suggested that both DENV1- and DENV3-circulating genotypes are in the genotype III group and remain closely related to the Indian clade. To the best of our knowledge, this is the first report on the genetic characterization of circulating DENVs in North Bengal, which may contribute to the study of dengue epidemic and pathogenesis.

Dengue virus 3 genotype I shows natural changes in heparan sulphate binding sites, cell interactions, and neurovirulence in a mouse model.

Dengue virus (DENV) is the most prevalent pathogen of the Flaviviridae family. Due to the considerable increase in DENV incidence and spread, symptoms such as CNS involvement have increased. Heparan sulphate (HS) was the first molecule identified as an adhesion factor for DENV in mammalian cells. Viral phenotypes with different HS interactions are associated with various clinical symptoms, including neurological alterations. Here, using in silico analyses, in vitro studies, and the in vivo mouse model, we characterized two natural circulating DENV3 genotype I (GI) lineage 1 (L1) in Brazil-DENV3 MG-20 (from Minas Gerais) and DENV3 PV_BR (from Rondônia) that present divergent neurovirulent profiles and sensitivity to sulphated molecules. We identified substitutions at the viral envelope (E) in positions 62 and 123 as likely responsible for the differences in neurovirulence. The E62K and E123Q substitutions in DENV3 MG-20 and DENV3 PV_BR, respectively, greatly influenced in silico electrostatic density and heparin docking results. In vivo, mice inoculated with DENV3 MG-20 died, but not those infected with DENV3 PV_BR. The clinical symptoms, such as paralysis of the lower limbs and meningoencephalitis, and histopathology, also differed between the inoculated groups. In vitro heparin and heparinases assays further demonstrated the biological impact of these substitutions. Other characteristics that have been previously associated with alterations in cell tropism and neurovirulence, such as changes in the size of lysis plaques and differences in cytopathic effects in glioblastoma cells, were also observed.

Emergence of the Asian lineage dengue virus type 3 genotype III in Malaysia.

BACKGROUND: Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally. RESULTS: Phylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5-553I/M, NS5-629 T, and NS5-820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013. CONCLUSIONS: Distinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.

Dengue Fever in Burkina Faso, 2016.

We report 1,327 probable cases of dengue in Burkina Faso in 2016. Of 35 serum samples tested by a trioplex test, 19 were confirmed dengue virus (DENV)‒positive: 11 DENV-2, 6 DENV-3, 2 nontypeable, and 1 DENV-2/DENV-3 co-infection. Molecular testing should be conducted to correctly identify causative agents in this complex infectious disease landscape.

Outbreak investigation of fever mimicking dengue in Havelock Island, an important tourist destination in the Andaman & Nicobar Archipelago, 2014.

An upsurge of fever cases of unknown origin, but resembling dengue and leptospirosis was reported in Havelock, Andaman & Nicobar Islands, an important tourism spot, during May 2014. Investigations were carried out to determine the aetiology, and to describe the epidemiology of the outbreak. The data on fever cases attending Primary Health Centre (PHC), Havelock showed that the average number of cases reporting per week over the last 2 years was 46·1 (95% confidence interval 19·4-72·9). A total of 27 (43·5%) patients out of the 62 suspected cases were diagnosed as having DENV infection based on a positive enzyme immunoassay or reverse transcriptase-polymerase chain reaction. The overall attack rate was 9·4 cases/1000 population and it ranged between 2·8 and 18·8/1000 in different villages. The nucleotide sequencing showed that the virus responsible was DENV-3. DENV-3 was first detected in the Andaman & Nicobar Islands in 2013 among wharf workers in Port Blair and within a year it has spread to Havelock Island which is separated from South Andaman by 36 nautical miles.

Urban epidemic of dengue virus serotype 3 infection, Senegal, 2009.

An urban epidemic of dengue in Senegal during 2009 affected 196 persons and included 5 cases of dengue hemorrhagic fever and 1 fatal case of dengue shock syndrome. Dengue virus serotype 3 was identified from all patients, and Aedes aegypti mosquitoes were identified as the primary vector of the virus.

Re-Emergence of DENV-3 in French Guiana: Retrospective Analysis of Cases That Circulated in the French Territories of the Americas from the 2000s to the 2023-2024 Outbreak.

French Guiana experienced an unprecedented dengue epidemic during 2023-2024. Prior to the 2023-2024 outbreak in French Guiana, DENV-3 had not circulated in an epidemic manner since 2005. We therefore studied retrospectively the strains circulating in the French Territories of the Americas (FTA)-French Guiana, Guadeloupe, and Martinique-from the 2000s to the current epidemic. To this end, DENV-3 samples from the collection of the National Reference Center for Arboviruses in French Guiana (NRCA-FG) were selected and sequenced using next-generation sequencing (NGS) based on Oxford Nanopore Technologies, ONT. Phylogenetic analysis showed that (i) the 97 FTA sequences obtained all belonged to genotype III (GIII); (ii) between the 2000s and 2013, the regional circulation of the GIII American-I lineage was the source of the FTA cases through local extinctions and re-introductions; (iii) multiple introductions of lineages of Asian origin appear to be the source of the 2019-2021 epidemic in Martinique and the 2023-2024 epidemic in French Guiana. Genomic surveillance is a key factor in identifying circulating DENV genotypes, monitoring strain evolution, and identifying import events.

Unraveling Dengue Virus Diversity in Asia: An Epidemiological Study through Genetic Sequences and Phylogenetic Analysis.

Dengue virus (DENV) is the causative agent of dengue. Although most infected individuals are asymptomatic or present with only mild symptoms, severe manifestations could potentially devastate human populations in tropical and subtropical regions. In hyperendemic regions such as South Asia and Southeast Asia (SEA), all four DENV serotypes (DENV-1, DENV-2, DENV-3, and DENV-4) have been prevalent for several decades. Each DENV serotype is further divided into multiple genotypes, reflecting the extensive diversity of DENV. Historically, specific DENV genotypes were associated with particular geographical distributions within endemic regions. However, this epidemiological pattern has changed due to urbanization, globalization, and climate change. This review comprehensively traces the historical and recent genetic epidemiology of DENV in Asia from the first time DENV was identified in the 1950s to the present. We analyzed envelope sequences from a database covering 16 endemic countries across three distinct geographic regions in Asia. These countries included Bangladesh, Bhutan, India, Maldives, Nepal, Pakistan, and Sri Lanka from South Asia; Cambodia, Laos, Myanmar, Thailand, and Vietnam from Mainland SEA; and Indonesia, the Philippines, Malaysia, and Singapore from Maritime SEA. Additionally, we describe the phylogenetic relationships among DENV genotypes within each serotype, along with their geographic distribution, to enhance the understanding of DENV dynamics.

Understanding dengue outbreaks in Rajshahi district, Bangladesh: A comprehensive case study.

Background and aims: The 2023 dengue outbreak in Bangladesh marked an unprecedented increase in fatalities, particularly in Dhaka, and demonstrated extensive prevalence nationwide, including Rajshahi district. Dengue fever remains a significant public health challenge in Southeast Asia, with complex epidemiological patterns. Previous research has mainly focused on den serotypes in Dhaka. Therefore, this study aims to identify serotypes in the Rajshahi district under endemic conditions. Methods: Blood samples from suspected dengue patients were collected at Rajshahi Medical College Hospital. Initial rapid detection of dengue-positive cases was performed using (Nonstructural Protein 1 L) NS1, (Immunoglobulin G) IgG, and (Immunoglobulin M) IgM tests. Upon confirmation of dengue positivity, viral RNA was extracted for molecular testing. The dengue serotype was identified using real-time reverse transcription-polymerase chain reaction (rRT-PCR). Results: The study revealed that 93.3 % of the patient were infected with (Dengue virus type 2) DENV2 and rest 6.7 % of the patient were (Dengue virus type 3) DENV3 among 30 dengue positive patients. Demographic observations show the distribution of dengue over nine upazilas. In Paba upazila, we found two DENV3 alongside DENV2. Conclusion: The study concludes that the 2023 dengue outbreak in Rajshahi district, Bangladesh, predominantly involved the DENV2 serotype. Geospatial analysis underscores the importance of understanding regional distribution patterns to enhance targeted interventions against dengue fever in endemic areas.

Singapore's Dengue Outbreak Amidst the COVID-19 Pandemic: Challenges, Responses, and Lessons.

Dengue outbreaks have been documented in Singapore since 1901, occurring almost annually in the 1960s and disproportionately affecting the paediatric population. In January 2020, virological surveillance detected a shift from DENV-2, which was the previous dominant strain, to DENV-3. As of 20 September 2022, 27,283 cases have been reported in 2022. Singapore is currently also responding to the COVID-19 pandemic, overcoming another wave of infections with 281,977 cases recorded in the past two months as of 19 September 2022. While Singapore has adopted several policies and interventions to combat dengue, primarily through environmental control but also innovations such as the Wolbachia mosquito programme, there is a need for further efforts to deal with the dual threat of dengue and COVID-19. Drawing lessons from Singapore's experience, countries facing such dual epidemics should enact clear policy responses, including establishing a multisectoral dengue action committee and action plan prior to potential outbreaks. Key indicators should be agreed upon and tracked at all healthcare levels as part of dengue surveillance and incorporated into the national health information system. Digitizing dengue monitoring systems and implementing telemedicine solutions are innovative measures that would facilitate the response to dengue in the context of restrictions during the COVID-19 pandemic that hinder the detection and response to new cases. There is a need for greater international collaboration in reducing or eradicating dengue in endemic countries. Further research is also required on how best to establish integrated early warning systems and extend our knowledge of the effects of COVID-19 on dengue transmission in affected countries.

S-Adenosyl-l-Homocysteine Exhibits Potential Antiviral Activity Against Dengue Virus Serotype-3 (DENV-3) in Bangladesh: A Viroinformatics-Based Approach.

Dengue outbreak is one of the concerning issues in Bangladesh due to the annual outbreak with the alarming number of death and infection. However, there is no effective antiviral drug available to treat dengue-infected patients. This study evaluated and screened antiviral drug candidates against dengue virus serotype 3 (DENV-3) through viroinformatics-based analyses. Since 2017, DENV-3 has been the predominant serotype in Bangladesh. We selected 3 non-structural proteins of DENV-3, named NS3, NS4A, and NS5, as antiviral targets. Protein modeling and validation were performed with VERIFY-3D, Ramachandran plotting, MolProbity, and PROCHECK. We found 4 drug-like compounds from DRUGBANK that can interact with these non-structural proteins of DENV-3. Then, the ADMET profile of these compounds was determined by admetSAR2, and molecular docking was performed with AutoDock, SWISSDOCK, PatchDock, and FireDock. Furthermore, they were subjected to molecular dynamics (MD) simulation study using the DESMOND module of MAESTRO academic version 2021-4 (force field OPLS_2005) to determine their solution's stability in a predefined body environment. Two drug-like compounds named Guanosine-5'-Triphosphate (DB04137) and S-adenosyl-l-homocysteine (DB01752) were found to have an effective binding with these 3 proteins (binding energy > 33.47 KJ/mole). We found NS5 protein was stable and equilibrated in a 100 ns simulation run along with a negligible (<3Å) root-mean-square fluctuation value. The root-mean-square deviation value of the S-adenosyl-l-homocysteine-NS5 complex was less than 3Å, indicating stable binding between them. The global binding energy of S-adenosyl-l-homocysteine with NS5 was -40.52 KJ/mole as ∆G. Moreover, these 2 compounds mentioned above are non-carcinogenic according to their ADMET (chemical absorption, distribution, metabolism, excretion, and toxicity) profile (in silico). These outcomes suggest the suitability of S-adenosyl-l-homocysteine as a potential drug candidate for dengue drug discovery research.

A Six Years (2010-2016) Longitudinal Survey of the Four Serotypes of Dengue Viruses in Lao PDR.

Dengue fever is the most prevalent arthropod-borne viral infection of humans in tropical and subtropical countries. Since 1979, dengue has been reported to be endemic in the Lao People's Democratic Republic (PDR), as in many countries in Southeast Asia, with a complex circulation of the four dengue viruses' serotypes (DENV-1 to DENV-4). By sequencing the complete envelope protein, we explored a panel of samples from five Lao Provinces (Vientiane capital, Luangprabang, Bolikhamxay, Saravane, Attapeu) to enrich knowledge about the co-circulation of DENVs in Lao PDR between 2010 and 2016. Phylogenetic analyses highlighted the specific circulation of DENV-1 genotype I, DENV-2 genotype Asian I, DENV-4 genotype I and the co-circulation of DENV-3 genotype II and III. The continuous co-circulation of the four serotypes was underlined, with genotype or cluster shifts among DENV-3 and DENV-1. These data suggested the emergence or re-emergence of DENV strains associated with epidemic events, potentially linked to the exchanges within the territory and with neighboring countries. Indeed, the increasing local or regional connections favored the dissemination of new isolates or new clusters around the country. Since 2012, the surveillance and alert system created in Vientiane capital by the Institut Pasteur du Laos appears to be a strategic tool for monitoring the circulation of the four serotypes, especially in this endemic country, and allows for improving dengue epidemiological knowledge to anticipate epidemic events better.

Circulation of DENV-3 Genotype 3 during 2017 to 2018 in Delhi: A Single-Center Hospital-Based Study.

Introduction Delhi is hyperendemic for dengue virus (DENV) where all the four DENV have previously been reported. A constant vigilance of circulating DENV serotypes is important in surveillance, since the introduction of a new variant to areas affected by preexisting serotypes constitutes a risk factor for dengue hemorrhagic fever and dengue shock syndrome. Objectives This retrospective study was performed with an objective to determine the circulating serotype and genotype of DENV in acute phase blood samples of patients who have reported to a tertiary liver care hospital in New Delhi during the last 2 years (2017-2018). Methods The data of clinician-initiated testing for dengue nonstructural protein 1 (NS1) antigen (Ag) was searched in the institutional hospital information system. The serum sample of dengue NS1 Ag-positive cases confirmed by enzyme-linked immunosorbent assay (ELISA; PANBIO, Gyeonggi-do, ROK) and a fever duration of less than 5 days were retrieved from the laboratory archive. The DENV serotyping on these sample was performed by reverse transcriptase polymerase chain reaction (RT-PCR). Sequencing and phylogenetic analysis was done for the capsid premembrane (CprM) region to determine the genotype. Results A total of 440 acute-phase samples were received. Twenty one (4.77%) were positive for dengue NS1 Ag with a mean age of 35.1 years and male-to-female ratio of 1.1:1. Eight cases (38.09%) were positive by dengue RT-PCR and all belonged to DENV-3 serotypes. Phylogenetic tree analysis revealed DENV-3 clustered to genotype III with 100% homology with 2008 Indian subcontinent strain. Conclusion This study revealed circulation of DENV-3, genotype III in Delhi from 2017 to 2018, similar to the 2008 viral type. Virological surveillance is an important exercise to be done for viral infections with public threat and outbreak potential.

In Silico Comparative Analysis of Predicted B Cell Epitopes against Dengue Virus (Serotypes 1-4) Isolated from the Philippines.

Dengue is a viral mosquito-borne disease that rapidly spreads in tropical and subtropical countries, including the Philippines. One of its most distinguishing characteristics is the ability of the Dengue Virus (DENV) to easily surpass the innate responses of the body, thus activating B cells of the adaptive immunity to produce virus-specific antibodies. Moreover, Dengvaxia® is the only licensed vaccine for DENV, but recent studies showed that seronegative individuals become prone to increased disease severity and hospitalization. Owing to this limitation of the dengue vaccine, this study determined and compared consensus and unique B cell epitopes among each DENV (1-4) Philippine isolate to identify potential areas of interest for future vaccine studies and therapeutic developments. An in silico-based epitope prediction of forty (40) DENV 1-4 strains, each serotype represented by ten (10) sequences from The National Center for Biotechnology Information (NCBI), was conducted using Kolaskar and Tongaonkar antigenicity, Emini surface accessibility, and Parker hydrophilicity prediction in Immune Epitope Database (IEDB). Results showed that five (5) epitopes were consensus for DENV-1 with no detected unique epitope, one (1) consensus epitope for DENV-2 with two (2) unique epitopes, one (1) consensus epitope for DENV-3 plus two (2) unique epitopes, and two (2) consensus epitopes and one (1) unique epitope for DENV-4. The findings of this study would contribute to determining potential vaccine and diagnostic marker candidates for further research studies and immunological applications against DENV (1-4) Philippine isolates.

Functional analysis of differentially expressed long non-coding RNAs in DENV-3 infection and antibody-dependent enhancement of viral infection.

Dengue fever, as a mosquito-borne viral disease widely spread in tropical and subtropical regions, remarkably threatens public health, while the mechanism involved in host-DENV interaction has not been fully elucidated. Firstly, we analyzed the expression levels of long non-coding RNAs (lncRNAs) in THP-1 cells after DENV-3 infection and Antibody- Dependent Enhancement of viral infection (ADE-VI) by RNA-Seq. Secondly, through the RT-qPCR to confirm those differentially expressed (DE) lncRNAs. Then, we also analyzed the competitive endogenous RNA (CeRNA) regulatory network of DE lncRNAs. Finally, we predicted the encode ability of DE lncRNAs. It was found that on the X and Y chromosomes, the expression levels of lncRNAs in THP-1 cells after ADE-VI were significantly different from those in the negative control and the DENV-3 infection groups. There were 71 DE lncRNAs after DENV-3 infection, including 42 up-regulated and 29 down-regulated lncRNAs. A total of 70 DE lncRNAs after ADE-VI were detected, including 38 up-regulated and 32 down- regulated lncRNAs. After ADE-VI and DENV-3 infection, there were 35 DE lncRNAs, including 11 up-regulated and 24 down-regulated lncRNAs. The analysis of the CeRNA regulatory network of DE lncRNAs revealed that, TRIM29, STC2, and IGFBP5 were correlated with the ADE-VI. Additionally, it was found that lncRNAs not only participated in the CeRNA regulatory network, but also maybe encoded small peptides. Our findings provided clues for further investigation into the lncRNAs associated antiviral mechanism of ADE-VI and DENV-3 infection.

Development of a Singleplex Real-Time Reverse Transcriptase PCR Assay for Pan-Dengue Virus Detection and Quantification.

Dengue virus (DENV) infection is a significant global health problem. There are no specific therapeutics or widely available vaccines. Early diagnosis is critical for patient management. Viral RNA detection by multiplex RT-PCR using multiple pairs of primers/probes allowing the simultaneous detection of all four DENV serotypes is commonly used. However, increasing the number of primers in the RT-PCR reaction reduces the sensitivity of detection due to the increased possibility of primer dimer formation. Here, a one tube, singleplex real-time RT-PCR specific to DENV 3'-UTR was developed for the detection and quantification of pan-DENV with no cross reactivity to other flaviviruses. The sensitivity of DENV detection was as high as 96.9% in clinical specimens collected at the first day of hospitalization. Our assay provided equivalent PCR efficiency and RNA quantification among each DENV serotype. The assay's performance was comparable with previously established real-time RT-PCR targeting coding sequences. Using both assays on the same specimens, our results indicate the presence of defective virus particles in the circulation of patients infected with all serotypes. Dual regions targeting RT-PCR enhanced the sensitivity of viral genome detection especially during the late acute phase when viremia rapidly decline and an incomplete viral genome was clinically evident.

Emergence of a Novel Dengue Virus 3 (DENV-3) Genotype-I Coincident with Increased DENV-3 Cases in Yangon, Myanmar between 2017 and 2019.

Dengue fever, caused by the mosquito-borne dengue virus (DENV), has been endemic in Myanmar since 1970 and it has become a significant public health burden. It is crucial that circulating DENV strains are identified and monitored, and that their transmission efficiency and association with disease severity is understood. In this study, we analyzed DENV-1, DENV-2, DENV-3, and DENV-4 serotypes in 1235 serum samples collected in Myanmar between 2017 and 2019. Whole-genome sequencing of DENV-1-4 demonstrated that most DENV-1-4 strains had been circulating in Myanmar for several years. We also identified the emergence of DENV-3 genotype-I in 2017 samples, which persisted through 2018 and 2019. The emergence of the strain coincided with a period of increased DENV-3 cases and marked changes in the serotype dynamics. Nevertheless, we detected no significant differences between serum viral loads, disease severity, and infection status of individuals infected with different DENV serotypes during the 3-year study. Our results not only identify the spread of a new DENV-3 genotype into Yangon, Myanmar, but also support the importance of DENV evolution in changing the epidemic dynamics in endemic regions.

Sweeping analysis of transcript profile in dengue virus serotype 3 infection and antibody-dependent enhancement of infection.

Dengue virus infection mainly causes dengue hemorrhagic fever (DHF) and/or dengue shock syndrome (DSS). However, ADE (antibody-dependent enhancement) is one of the main pathogenic factors, and its pathogenic mechanism has not been fully elucidated. Recently, with the development of high-throughput sequencing, an increased number of RNAs have been confirmed to play a vital regulatory role in the process of virus infection. However, there is a lack of research on dengue virus infection and ADE. In this study, we used RNA-Seq to detect differentially expressed RNAs (DE RNAs) profiles in mock-infected, DENV-3-infected, and ADE-infected THP-1 cells. Firstly, we found 69 circRNAs, 259 miRNAs, and 18 mRNAs were differentially expressed in THP-1 vs DENV-3. In THP-1 vs ADE, 94 circRNAs, 263 miRNAs, and 111 mRNAs were differentially expressed. In DENV-3 vs ADE, 68 circRNAs, 105 miRNAs, and 94 mRNAs were differentially expressed. Functional enrichment analysis of these DE RNAs mainly focused on immune system, viral infectious diseases, cytokine-cytokine receptor interactions, and NOD/RIG-I-like receptor signaling pathways. In DENV-3 vs ADE, notably, the expression of HBB was up-regulated, which was a Fcγ Receptor-mediated phagocytosis protein. Additionally, we predicted the encoding ability of DE circRNAs, and it was found that a small peptide was encoded by novel_circ_001562 and that its amino acid sequence was consistent with that of DDX60L, which is a class of interferon-stimulated genes. Finally, we constructed the ceRNA regulatory network pathway. Therefore, our study provides a new strategy for further investigation on DENV-host interactions.