So we're going to spend several blog posts now focusing in on the E gene and understanding it genetically, structurally and it's role immunologically...as there were several topics covering this during NIAID-DVI...
Recent Advances in our understanding of how human antibodies neutralize dengue viruses
Aravinda de Silva
University of North Carolina School of Medicine
From the Abstract:
Ten years ago it was known that people exposed to dengue virus developed strongly neutralizing antibodies against the homologous serotype but the molecular basis of neutralization was not known. Over the course of the subsequent decade several groups have studied the properties of DENV-specific human serum antibodies (Abs) derived from plasma cells and monoclonal Abs (mAbs) derived from memory B-cells. These studies demonstrated:
The 'maturation state' of the virus influences the ability to infect cells and antibodies to neutralize DENVs...this is why DENV neutralization titers are notoriously variable.
Recent Advances in our understanding of how human antibodies neutralize dengue viruses
Aravinda de Silva
University of North Carolina School of Medicine
From the Abstract:
Ten years ago it was known that people exposed to dengue virus developed strongly neutralizing antibodies against the homologous serotype but the molecular basis of neutralization was not known. Over the course of the subsequent decade several groups have studied the properties of DENV-specific human serum antibodies (Abs) derived from plasma cells and monoclonal Abs (mAbs) derived from memory B-cells. These studies demonstrated:
- The dominant human Ab response is serotype cross-reactive and non-neutralizing
- While functionally important, neutralizing Abs are a small 'component' to the entire response.
- Human neutralizing Abs bind to complex epitopes centered in the hinge region between domain I and II (DI and DII) of the dengue E gene.
- Humans also produce strong neutralizing Abs that bind in domain III (DIII) of the E protein.
- Replicating viruses stimulate DI/DII hinge antibodies whereas recombinant antigens trigger DIII directed neutralizing antibody response.
The 'maturation state' of the virus influences the ability to infect cells and antibodies to neutralize DENVs...this is why DENV neutralization titers are notoriously variable.
