Significance: Due to difficulty in obtaining relevant samples and low levels of dengue virus (DENV) present in patients, it has been difficult to characterize the properties of virions circulating in humans. We characterized DENV1 directly from early acute primary dengue samples and from their cell culture isolates. We observed that virions in humans are more infectious and mature as compared with their cell culture isolates. DENV1 cell culture isolates were hypersensitive to neutralization by human antibodies. Cross-reactive fusion loop antibodies and heterotypic immune sera poorly neutralized plasma DENV1. Identical genome sequences showed that the phenotypic differences are due to the differences in maturation state. The observed structural variation is a significant advance applicable to understanding vaccine failure and designing future vaccine strategies.
Zika virus (ZIKV) constitutes an increasing public health problem. Previous studies have shown that CD8+ T cells play an important role in ZIKV-specific protective immunity. We have previously defined antigenic targets of the ZIKV-specific CD8+ T cell response in humans. In this study, we characterized the quality and phenotypes of these responses by a combined use of flow cytometry and transcriptomic methods, using PBMCs from donors deriving from different geographical locations collected in the convalescent phase of infection. We show that ZIKV-specific CD8+ T cells are characterized by a polyfunctional IFN-γ signature with upregulation of TNF-α, TNF receptors, and related activation markers, such as CD69, as well as a cytotoxic signature characterized by strong upregulation of GZMB and CRTAM. The signature is stable and not influenced by previous dengue virus exposure, geographical location, or time of sample collection postinfection. To our knowledge, this work elucidates the first in-depth characterization of human CD8+ T cells responding to ZIKV infection.
The number of cases and severity of disease associated with dengue infection in Sri Lanka has been increasing since 1989, when the first epidemic of dengue hemorrhagic fever was recorded. We identified a new dengue virus 1 strain circulating in Sri Lanka that coincided with the 2009 dengue epidemic.