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Dengue Virus Symptoms Muted by Adaptive Immune Response, Gene Expression Study Suggests

NEW YORK (GenomeWeb) – The severity of symptoms patients develop after a dengue virus (DENV) infection appears to be influenced by adaptive immune response, new research suggests.

Researchers from France, Cambodia, and Singapore tracked blood gene expression and immunological patterns in dozens of children from Cambodia who were infected with serotype 1 DENVs, including several symptom-free children. Their findings, appearing online today in Science Translational Medicine, suggest that dengue infection symptoms typically coincide with diminished expression of genes contributing to apoptosis and enhanced development of plasma cells producing low-affinity antibodies.  

On the other hand, the team saw transcriptional and immune cell signatures associated with more pronounced apoptotic activity, or controlled cell death, in the asymptomatic dengue cases, along with distinct antigen presentation patterns and prominent T cell activation.

"[O]ur 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," Pasteur Institute researchers Anavaj Sakuntabhai and Tineke Cantaert, co-corresponding authors on the study, and their colleagues wrote.

Along with measurements of DENV RNA in blood samples from 76 Cambodian children with symptomatic DENV infections and nine children with asymptomatic infections, the researchers profiled gene expression in peripheral blood mononuclear cells from the children. They also tracked antibody, cytokine, and other immune phenotypes in this purified blood immune cell collection.

When the team compared Affymetrix array-based expression profiles in samples from eight of the asymptomatic children and 25 of the children showing dengue symptoms, it identified more than 1,000 genes with enhanced expression in the symptom-free children and another 618 genes with muted expression in the asymptomatic DENV infection group.

That differentially expressed gene set included components of several immune-related pathways, the researchers reported. And the asymptomatic cases remained transcriptionally distinct from uninfected individuals, according to their comparisons with published expression data for Nicaraguan children with or without DENV infections.

Although viral load, inflammatory response, and innate immune activity were generally comparable across the Cambodian dengue virus cases, with or without symptoms, the team did detect differences when it came to antigen presentation, T cell activation, and other adaptive immune features.

In particular, the symptom-free children appeared to have higher levels of T lymphocyte signaling and apoptotic activity, while clinical dengue cases were more likely to be marked by plasma cell differentiation, diminished B cell inhibition, and a boost in blood levels of certain antibodies.

The findings may not necessary represent immune patterns in adult DENV infection cases, the authors cautioned. Even so, they argued that the results "contribute to our understanding of the development of symptomatic dengue and will lead to novel strategies for future vaccine development."

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