Lack of Clinical Manifestations in Asymptomatic Dengue Infection Is Attributed to Broad Down-Regulation and Selective Up-Regulation of Host Defence Response Genes

Yeo, Adeline; Azhar, Nur Atiqah; Yeow, Wanyi; Talbot, C. Conover; Khan, Mohammad Asif; Shankar, Esaki Muthu; Rathakrishnan, Anusyah; Azizan, Azliyati; Wang, Seok Mui; Lee, Siew Kim; Fong, Mun Yik; Manikam, Rishya; Sekaran, Shamala Devi

doi:10.1371/journal.pone.0092240

Cited by 33 publications

(29 citation statements)

References 74 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…However, we cannot delineate which of the observed phenomena can be attributed to antigen specific responses. Therefore, future studies using tools to identify DENV-specific T cells and B cells in strictly asymptomatic individuals will be of great value (38,53) One previous report analyzing differential gene expression in asymptomatic DENV-infected individuals investigated patients in the convalescent phase of the disease, as demonstrated by the absence of detectable viral loads (57). Unsurprisingly, they found that most genes related to host defense mechanisms were downregulated.…”

Section: Discussionmentioning

confidence: 99%

Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

et al. 2017

View full text Add to dashboard Cite

Clinical symptoms of dengue virus (DENV) infection, the most prevalent arthropod-borne viral disease, range from classical mild dengue fever to severe, life-threatening dengue shock syndrome. However, most DENV infections cause few or no symptoms. Asymptomatic DENV-infected patients provide a unique opportunity to decipher the host immune responses leading to virus elimination without negative impact on an individual's health. We used an integrated approach of transcriptional profiling and immunological analysis to compare a Cambodian population of strictly asymptomatic viremic individuals with clinical dengue patients. Whereas inflammatory pathways and innate immune response pathways were similar between asymptomatic individuals and clinical dengue patients, expression of proteins related to antigen presentation and subsequent T cell and B cell activation pathways was differentially regulated, independent of viral load and previous DENV infection history. Feedback mechanisms controlled the immune response in asymptomatic viremic individuals, as demonstrated by increased activation of T cell apoptosis-related pathways and FcγRIIB (Fcγ receptor IIB) signaling associated with decreased anti-DENV-specific antibody concentrations. Together, our data illustrate that symptom-free DENV infection in children is associated with increased activation of the adaptive immune compartment and proper control mechanisms, leading to elimination of viral infection without excessive immune activation, with implications for novel vaccine development strategies.

show abstract

Section: Discussionmentioning

confidence: 99%

Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Studies of rotavirus gastroenteritis have found that serum TNF-a is associated significantly with diarrhoea incidence when compared to healthy controls and controls with non-viral diarrhoea [19,20]. Other viral infections, including hepatitis B and dengue virus, induce different proinflammatory cytokine gene expression in symptomatic compared to asymptomatic individuals [21,22]. In the case of dengue, symptomatic individuals had higher expression of many proinflammatory cytokine genes compared to asymptomatic individuals, suggesting that some of dengue's most severe outcomes may be caused partially by an inflammatory response [22].…”

Section: Discussionmentioning

confidence: 99%

“…Other viral infections, including hepatitis B and dengue virus, induce different proinflammatory cytokine gene expression in symptomatic compared to asymptomatic individuals [21,22]. In the case of dengue, symptomatic individuals had higher expression of many proinflammatory cytokine genes compared to asymptomatic individuals, suggesting that some of dengue's most severe outcomes may be caused partially by an inflammatory response [22]. Indeed, cytokines are thought to cause diarrhoea in other infections without primary gastrointestinal tropism (e.g.…”

Section: Discussionmentioning

confidence: 99%

Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding

Newman

Moe

Kirby

et al. 2016

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Summary Noroviruses (NoV) are the most common cause of epidemic gastroenteritis world-wide. NoV infections are often asymptomatic, although individuals still shed large amounts of NoV in their stool. Understanding the differences between asymptomatic and symptomatic individuals would help in elucidating mechanisms of NoV pathogenesis. Our goal was to compare the serum cytokine responses and faecal viral RNA titres of asymptomatic and symptomatic NoV-infected individuals. We tested serum samples from infected subjects (n = 26; 19 symptomatic, seven asymptomatic) from two human challenge studies of GI.1 NoV for 16 cytokines. Samples from prechallenge and days 1-4 post-challenge were tested for these cytokines. Cytokine levels were compared to stool NoV RNA titres quantified previously by reverse transcription–polymerase chain reaction (RT–qPCR). While both symptomatic and asymptomatic groups had similar patterns of cytokine responses, the symptomatic group generally exhibited a greater elevation of T helper type 1 (Th1) and Th2 cytokines and IL-8 post-challenge compared to the asymptomatic group (all P < 0·01). Daily viral RNA titre was associated positively with daily IL-6 concentration and negatively with daily IL-12p40 concentration (all P < 0·05). Symptoms were not associated significantly with daily viral RNA titre, duration of viral shedding or cumulative shedding. Symptomatic individuals, compared to asymptomatic, have greater immune system activation, as measured by serum cytokines, but they do not have greater viral burden, as measured by titre and shedding, suggesting that symptoms may be immune-mediated in NoV infection.

show abstract

“…The healthy controls were the household member of each dengue patient and there was significant increase in IL-4 levels in dengue patients. This study was done by Yeo et al 19 involving 29 pairs in the study.…”

Section: Why Il-4 Was Analysed?mentioning

confidence: 99%

Clinical Features and Significance of Cytokine Il-4 in Children With Dengue at a Tertiary Care Centre

Manoharan¹,

Pasupathy²,

Elayaraja³

et al. 2016

jebmh

View full text Add to dashboard Cite

BACKGROUND Dengue is a mosquito borne viral infection in tropical and subtropical regions caused by one of the four serotypes of dengue viruses (DENV1-DENV4). The consequences of DENV infection range from asymptomatic condition Dengue Fever (DF) or severe forms such as Dengue Haemorrhagic Fever (DHF) and Dengue Shock Syndrome (DSS). The host immune responses have been considered as the major factor responsible for dengue pathogenesis. Endothelial activation markers such as expression of adhesion molecules and receptors have been found to serve as biomarkers of severe dengue disease. In this study, the cytokine IL-4 is reviewed for its utility as potential biomarker of severe dengue disease. MATERIALS AND METHODS 120 children of paediatric age group from 1 month till 18 years of age with fever for more than 5 days with either dengue NS1 antigen or dengue IgM positive were included. 30 children who were admitted for noninfectious disease (e.g. surgery) without fever, any systemic illness and preexisting illness (tuberculosis, asthma) in SRMC and RI were taken as controls. Cases were classified as uncomplicated dengue (dengue without warning signs) and complicated dengue (dengue with warning signs and severe dengue). Clinical features and IL-4 (ELISA kit) were analysed and compared among the study population and statistical analysis done for the obtained data. RESULTS Analysis of clinical features among the study groups revealed children with complicated dengue had persistent vomiting (95%), abdominal pain (80%), decreased urine output (50%), bleeding manifestations (83.3%), hepatomegaly (70%), haemoconcentration with concurrent thrombocytopenia (93.3%), altered coagulation profile (28.3%), ICU stay (54.7%), leucocytosis (15%), leucopenia (66.6%) and normal leucocytes (18.4%). Analysis of IL-4 levels revealed children with complicated dengue showed >6 fold elevation in IL-4 levels (p=0.003). Mean IL-4 levels in complicated dengue group was also statistically significant (p=0.013). ROC curve for IL-4 indicated 50% reliability as predictor for dengue severity. CONCLUSION In our study, IL-4 levels were significantly higher in complicated dengue patients in comparison with uncomplicated dengue patients as well as normal control population. Though, this interleukin 4 can be used for assessing the severity of children with dengue, further studies with higher sample size are needed to advocate the routine use of IL-4 as a biomarker of dengue severity.

show abstract

Lack of Clinical Manifestations in Asymptomatic Dengue Infection Is Attributed to Broad Down-Regulation and Selective Up-Regulation of Host Defence Response Genes

Cited by 33 publications

References 74 publications

Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

Increased adaptive immune responses and proper feedback regulation protect against clinical dengue

Norovirus in symptomatic and asymptomatic individuals: cytokines and viral shedding

Clinical Features and Significance of Cytokine Il-4 in Children With Dengue at a Tertiary Care Centre

Contact Info

Product

Resources

About