Immune mediated and inherited defences against flaviviruses.
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, Flv.


OBJECTIVE
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.


METHODS
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 intracellularly 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 flavivirus-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.
Brinton
M A
MA
Department of Biology, Georgia State University, Atlanta 30302-4010, USA. biomab@panther.gsu.edu
Kurane
I
I
Mathew
A
A
Zeng
L
L
Shi
P Y
PY
Rothman
A
A
Ennis
F A
FA
D000818:Animals; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D005416:Flavivirus / Q000235:genetics* / Q000276:immunology*; D018177:Flavivirus Infections / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D051379:Mice; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology
D018985:Epitopes, B-Lymphocyte; D018984:Epitopes, T-Lymphocyte; D014764:Viral Proteins