Double blow for dengue

Nicaraguan children provided data for the study

Nicaraguan children provided data for the study

The reason dengue fever can be more severe a second time round is due to the genetic make-up of the virus, researchers at Berkeley have found. The results may help predict outbreaks of dengue and allow future treatments to be better targeted.

Long-term studies assessing children’s immune systems in Nicaragua showed individual response to the virus depends on date of birth and previous dengue infections. These factors could be the difference between contracting a mild fever and fatal circulatory failure.

New updates

Our immune systems are updated every time we encounter a new disease. Because viruses evolve over time, the antibodies we create may not match the disease if it strikes again – scientists working on dengue are effectively aiming at a moving target from a moving platform.

Dengue virus comes in four varieties, or serotypes. Infection with one of these types elicits a specific response from the immune system, providing protection against that one type and limited protection against the three others.

If a person is then infected with another serotype, the body is able to recognise the disease and sends the weak antibodies. Instead of neutralising the viruses, the antibodies bind to them and spread the infection within the immune response cells. This Trojan horse effect prevents the immune system from launching a counter-attack and results in the virus taking hold of the body faster than before.

“With the second infection, the antibodies sort of recognise the new type of viruses, but not well enough to clear them from the system,” says Molly OhAinle, study leader at UC Berkeley’s School of Public Health.

Immunity from experience

The study looked at two sets of independent data – one examined children admitted to hospital with dengue between 2005 and 2009, the other had collected blood samples annually from 3,800 children since 2004. By analysing the viruses’ genomes across this time, scientists detected the genetic mutations that occurred as the severity of the disease changed.

Different strains of dengue have been endemic at certain times, for example dengue type 3 was prevalent in 1994-1998. The study demonstrated that children exposed to the virus at this time were at greater risk from a subtype of dengue virus 2. Similarly, virus 1, which circulated in 2002-2005, increased the risk of severe infection from a subtype of virus 2.

“We showed for dengue that both the subtype of virus you get infected with and whether your body has antibodies to another type of virus matter,” says Matthew Henn, director of viral genomics at the Broad Institute of Harvard University.

New design

Designing therapies for dengue that depend on antibodies have the potential to induce the wrong response and turn the infection critical. Current treatments therefore include protection for all four serotypes but results from this research could eliminate that need.

Predicting the genetic trajectory of a virus and knowing how varieties of dengue thrive in certain immune systems will “enable us to more accurately predict which lineages will likely proliferate in different human populations at a given time,” says Henn. “I’m hopeful that such predictions will translate to therapies.”

Photo credit: craigCoutier on Flickr

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