Thursday, June 23, 2016

Nature Immunology: Previous Dengue Infection May Make Zika Infection Worse


It's an idea that has been bandied about for many months, and strongly hinted at in a study published last April (see Dengue & Zika: Does What Goes Around, Come Around?), but we've new evidence today suggesting that those who have experienced a previous Dengue infection may be at greater risk of seeing a severe Zika virus infection.

Since Dengue is widespread in South and Central America, this could explain why Zika has hit those regions so hard over the past year. 

The idea is fairly simple, and it has previously been reported in sequential dengue infections. It is called ADE or Antibody Dependent Enhancement.

There are 4 distinct, but closely related, serotypes of the Dengue virus, and the first infection of any serotype is usually mild. The patient recovers with lifetime immunity, but remains susceptible to the other three serotypes.

When infected a second time,the host’s immune system - which already has neutralizing antibodies against the first DENV infection - misidentifies the second DENV infection as the first strain.

Rather than creating new neutralizing antibodies to fight the infection, it deploys its existing cross reactive, but non-neutralizing (read: ineffective) antibodies to the field of battle.

Zika is in the same family (Flaviviridae) of viruses as Dengue, and is genetically pretty close to the Dengue branch. So much so that diagnostic tests can have difficulty differentiating between the two infections.

So it makes sense that the same kind of ADE might occur when a Zika infection follows a Dengue infection. 

But lots of things can make sense.  It doesn't necessarily make it true.

While the results are preliminary, a study published today in the journal Nature Immunology suggests that existing dengue antibodies can recognize, and bind to, the Zika virus.

This could fool the body's immune system into sending unarmed (aka non-neutralizing) antibodies into battle against the invading Zika virus, and allow it to multiply rapidly. 

The full study may be read at:

Dengue virus sero-cross-reactivity drives antibody-dependent enhancement of infection with zika virus
Wanwisa Dejnirattisai, Piyada Supasa, Wiyada Wongwiwat, Alexander Rouvinski, Giovanna Barba-Spaeth,Thaneeya Duangchinda,Anavaj Sakuntabhai,Van-Mai Cao-Lormeau,Prida Malasit,Felix A Rey ,Juthathip Mongkolsapaya& Gavin R Screaton

Nature Immunology
Published online

Using a panel of human monoclonal antibodies (mAbs) to DENV, we showed that most antibodies that reacted to DENV envelope protein also reacted to ZIKV. Antibodies to linear epitopes, including the immunodominant fusion-loop epitope, were able to bind ZIKV but were unable to neutralize the virus and instead promoted ADE. Our data indicate that immunity to DENV might drive greater ZIKV replication and have clear implications for disease pathogenesis and future vaccine programs for ZIKV and DENV.

 (Continue . . . )

For a less technical overview, Imperial College has published a press release on this study:

Dengue virus exposure may amplify Zika infection

Imperial College London

Previous exposure to the dengue virus may increase the potency of Zika infection, according to research from Imperial College London.

The early-stage laboratory findings, published in the journal Nature Immunology, suggests the recent explosive outbreak of Zika may have been driven in part by previous exposure to the dengue virus.

The study, which included scientists from Institut Pasteur in Paris and Mahidol University in Bangkok, suggests the Zika virus uses the body's own defences as a 'Trojan horse', allowing it to enter a human cell undetected. Once inside the cell, it replicates rapidly.

Professor Gavin Screaton, senior author of the research and Dean of the Faculty of Medicine at Imperial, said: "Although this work is at a very early stage, it suggests previous exposure to dengue virus may enhance Zika infection. This may be why the current outbreak has been so severe, and why it has been in areas where dengue is prevalent. We now need further studies to confirm these findings, and to progress towards a vaccine."

A second study by the same team, published in Nature, suggests an antibody that works against the dengue virus may also neutralise Zika - providing a potential target for a vaccine.

Dengue fever has risen dramatically over recent decades and the virus is thought to cause around 390 million infections each year - with 40 per cent of the world's population living in areas of risk.

The dengue virus is similar to the Zika virus - they belong to the same viral family, called the Flaviviridae, and both are transmitted by the Aedes mosquito.

(Continue . . . )

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