Immune mediated and inherited defences against flaviviruses

Margo A. Brinton, Ichiro Kurane, Anuja Mathew, Lingling Zeng, Pei Yong Shi, Alan Rothman, Francis A. Ennis

Research output: Contribution to journalArticlepeer-review

30 Scopus citations


Background: Flavivirus infection elicits an abundant immune response in the host which is directed against a number of the viral proteins. Resistance to flavivirus-induced disease can also be controlled via a non-immune mechanism involving the product of a naturally occurring murine gene, Fly. Objectives: To review studies that have reported the mapping of epitopes on flavivirus proteins that elicit T- or B-cell immune responses in mice or humans and to discuss a possible mechanism for flavivirus-specific genetic resistance. Study design: Purified viral proteins and synthetic peptides were used to map B-cell epitopes. Purified proteins, vaccinia-expressed viral protein fragments and synthetic peptides were used to map T-cell epitopes. Congenic-resistant, C3H/RV and congenic susceptible, C3H/He mice and cell cultures were used to study the mechanism of genetic resistance to flavivirus infection. Results: T- and B-cell epitopes have been mapped to the E, NS1 and NS3 proteins of several flaviviruses. Immune responses to the C, PreM, NS2a, NS4a, and NS5 proteins have also been documented. Data suggest that the Flv gene product acts intracellulary to suppress the synthesis of viral genomic RNA. Conclusions: Although flavivirus infection elicits an abundant immune response, this response is not always rapid enough to protect the host from developing encephalitis. During secondary infections both the humoral and cellular navivirus-specific responses can confer protection. Dengue haemorrhagic fever (DHF) and dengue shock syndrome (DSS) appear to be caused by an overly vigorous immune response. In genetically resistant animals reduced production of virus results in a slower spread of the infection, which in turn allows time for the immune response to develop and to clear the infection before disease symptoms appear.

Original languageEnglish (US)
Pages (from-to)129-139
Number of pages11
JournalClinical and Diagnostic Virology
Issue number2-3
StatePublished - Jul 15 1998
Externally publishedYes


  • Flaviviral B-cell epitope
  • Flaviviral T-cell epitope
  • Flavivirus
  • Genetic resistance
  • Immune response
  • Non-structural viral protein
  • Structural viral protein

ASJC Scopus subject areas

  • Virology


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