Scientists explain why second dengue infection can be life-threatening

Scientists have decoded how the dengue virus evolves and are closer to understanding why the first dengue infection is often mild, while many second infections are life-threatening.

Researchers hypothesise that the antibodies produced in response to infection with one strain of the virus allows viruses of a different strain to enter undetected into cells, implying that antigenic differences between the stereotypes are important.

They have shown that while the long-held view that there are four genetically-distinct types of the dengue virus holds, far more important are the differences in their antigenic properties – the ‘coats’ that the viruses wear that help our immune systems identify them. When we become infected, our immune system sends out antibodies to try and identify the nature of the infection.

If it is a pathogen – a virus or bacteria – that we have previously encountered, the antibodies will recognise the invader by antigens on its surface and set of a cascade of defences to prevent the infection taking hold.

However, as pathogens evolve, they can change their antigens and disguise themselves against detection.

One of the unusual aspects of dengue is that in some cases when an individual becomes infected for a second time, rather than being immune to infection, the disease can be much more severe.

Researchers from the Dengue Antigenic Cartography Consortium, an international collaboration of leading dengue researchers, analysed 47 strains of dengue virus with 148 samples taken from both humans and primates to see whether they indeed fit into four distinct types.

They found a significant amount of antigenic difference within each dengue stereotype – in fact, the amount of difference within each stereotype was of a similar order to that between the different types.

This implies that an individual infected with one type may not be protected against anti-genically different viruses of the same type, and that in some cases the individual may be protected against some anti-genically similar strains of a different type.

“We were surprised at how much variation we saw not only between the existing four known types of dengue, but also within each type,” said Leah Katzelnick, a researcher from the Department of Zoology at the University of Cambridge in UK. “Now we can ask – and potentially answer – the interesting questions about how the virus evolves and, importantly, why a first dengue infection is often mild while many second infections are life-threatening,” said senior author Derek Smith, from University of Cambridge.