Dengue type 1 viruses circulating in humans are highly infectious and poorly neutralized by human antibodies

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Abstract
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.
Funding Information
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (1-R01-AI107731-01)
  • HHS | NIH | National Institute of Allergy and Infectious Diseases (P01 AI106695)
  • UNC virology training grant (T32AI007419)
  • Minority Student Development grant (5R25GM055336)

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