Recent advances in understanding dengue

Halstead, Scott B.

doi:10.12688/f1000research.19197.1

Cited by 89 publications

(75 citation statements)

References 136 publications

(135 reference statements)

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“…Secondary heterotypic dengue infection has been associated with severity due to the ineffective viral control of preexisting cross-reactive and low-affinity memory T cells (62). However, the risk of severe dengue in secondary heterotypic infection was not high in our studies (45,49) including the current study and some others (62). We have also analyzed T cell kinetics in the context of primary and secondary infection (Supplementary Figures 4A, B).…”

Section: Discussionmentioning

confidence: 75%

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

et al. 2020

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Background: The protective or pathogenic role of T lymphocytes during the acute phase of dengue virus (DENV) infection has not been fully understood despite its importance in immunity and vaccine development. Objectives: This study aimed to clarify the kinetics of T lymphocyte subsets during the clinical course of acute dengue patients. Study design: In this hospital-based cohort study, 59 eligible Vietnamese dengue patients were recruited and admitted. They were investigated and monitored for T cell subsets and a panel of clinical and laboratory parameters every day until discharged and at post-discharge from the hospital. Results: We described for the first time the kinetics of T cell response during the clinical course of DENV infection. Severe cases showed significantly lower levels of effector CD8 + T cells compared to mild cases at day −1 (p = 0.017) and day 0 (p = 0.033) of defervescence. After defervescence, these cell counts in severe cases increased rapidly to equalize with the levels of mild cases. Our results also showed a decline in total CD4 + T, Th1, Th1/17 cells during febrile phase of dengue patients compared to normal controls or convalescent phase. On the other hand, Th2 cells increased during DENV infection until convalescent phase. Cytokines such as interferon-γ, IL-12p70, IL-5, IL-23, IL-17A showed tendency to decrease on day 0 and 1 compared with convalescence and only IL-5 showed significance indicating the production during acute phase was not systemic.

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Section: Discussionmentioning

confidence: 75%

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

et al. 2020

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“…1. Clinical and epidemiological studies report the association of second heterotypic dengue infections as well as primary dengue infections in infants of dengue-immune mothers with dengue vascular permeability syndrome (DVPS) [20][21][22].…”

Section: Pathogenesis Of Denguementioning

confidence: 99%

“…Studies have shown that cytokine rise at presentation may indicate whether a patient is likely to develop severe dengue or not [133,134]. NS1-mediated cytokine release can be inhibited by TLR4-antagonist LPS-Rhodobacter sphaeroides, a gram-negative facultative photosynthetic bacterium which can lead to targeted therapy in future [22]. Another study has shown interest in the use of serum chymase levels as a predictive biomarker of DHF.…”

Section: Recent Insights Into Dengue Pathogenesis and Biomarkersmentioning

confidence: 99%

Current Understanding of the Pathogenesis of Dengue Virus Infection

et al. 2020

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The pathogenesis of dengue virus infection is attributed to complex interplay between virus, host genes and host immune response. Host factors such as antibody-dependent enhancement (ADE), memory cross-reactive T cells, anti-DENV NS1 antibodies, autoimmunity as well as genetic factors are major determinants of disease susceptibility. NS1 protein and anti-DENV NS1 antibodies were believed to be responsible for pathogenesis of severe dengue. The cytokine response of cross-reactive CD4+ T cells might be altered by the sequential infection with different DENV serotypes, leading to further elevation of pro-inflammatory cytokines contributing a detrimental immune response. Fcγ receptor-mediated antibody-dependent enhancement (ADE) results in release of cytokines from immune cells leading to vascular endothelial cell dysfunction and increased vascular permeability. Genomic variation of dengue virus and subgenomic flavivirus RNA (sfRNA) suppressing host immune response are viral determinants of disease severity. Dengue infection can lead to the generation of autoantibodies against DENV NS1antigen, DENV prM, and E proteins, which can cross-react with several self-antigens such as plasminogen, integrin, and platelet cells. Apart from viral factors, several host genetic factors and gene polymorphisms also have a role to play in pathogenesis of DENV infection. This review article highlights the various factors responsible for the pathogenesis of dengue and also highlights the recent advances in the field related to biomarkers which can be used in future for predicting severe disease outcome.

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“…DENV consists of a genome approximately 11kb nucleotides (nt) in length. The genome encodes three structural proteins, nucleocapsid (C), precursor membrane (prM) and envelope (E), as well as seven nonstructural proteins (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

Vector and cell-culture passaging of dengue clinical samples for virus isolation and amplification does not significantly change genome consensus or frequencies of intra-host viral variants

Fung

Pollett

et al. 2020

Preprint

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Intra-host single nucleotide variants (iSNVs) have been increasingly used in genomic epidemiology to increase phylogenetic resolution and reconstruct fine-scale outbreak dynamics. These analyses are preferably done on sequence data from direct clinical samples, but in many cases due to low viral loads, there might not be enough genetic material for deep sequencing and iSNV determination. Isolation of the virus from clinical samples with low passage number increases viral load, but to date, no studies have investigated how dengue virus (DENV) culture isolation from a clinical sample impacts the consensus sequence, and there is no information on the intra-host virus population changes that may result from viral isolation. In this study, we investigate consensus and iSNV frequency differences between DENV sequenced directly from clinical samples and their corresponding low-passage isolates. Twenty five DENV1 and DENV2 positive sera and their corresponding viral isolates (T.splendens inoculation and C6/36 passage) were obtained from a prospective cohort study in the Philippines. These were sequenced on MiSeq with minimum nucleotide depth of coverage of 1000x, and iSNVs were detected using LoFreq. For both DENV1 and DENV2, we found that the nucleotide call concordance (including called iSNVs with variant cutoff at 5%) between direct sera sample and its cultured virus was on average 99.99%. There were a maximum of one consensus nucleotide difference between clinical sample and isolate. Interestingly, we found that iSNV frequencies were also largely preserved between the samples, with an average difference in minor variant frequency of 6.8% (95CI: 3.6%-10%) and 9.6% (95CI: 7%-12.2%) for DENV1 and DENV2, respectively. Furthermore, we found no significant differences in either DENV1 or DENV2 between the sample pairs (clinical sample and isolate) in their number of iSNV positions per genome, or in the difference in variant frequencies (p=0.36 and p=0.13, respectively, F-test). Our results show that low-passage DENV isolates may be used for identification of the majority of their human-derived within-host variant populations, which are increasingly being used for precision tracking of DENV and other RNA viruses.

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Recent advances in understanding dengue

Cited by 89 publications

References 136 publications

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

Kinetics of CD4+ T Helper and CD8+ Effector T Cell Responses in Acute Dengue Patients

Current Understanding of the Pathogenesis of Dengue Virus Infection

Vector and cell-culture passaging of dengue clinical samples for virus isolation and amplification does not significantly change genome consensus or frequencies of intra-host viral variants

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