A previous encounter with a disease that is rampant across Latin America could leave people more vulnerable to the Zika virus. Antibodies to dengue virus, a relative of Zika, can interfere with the immune system’s response to Zika and boost the virus’s ability to replicate, according to work in two independent labs. That may help explain why the complications of Zika virus infections have been more severe in South and Central America than in previous epidemics elsewhere.
In some regions of Brazil, as many as 90% of people carry antibodies to dengue. Dengue viruses—there are four types—have an unusual relationship with the immune system. Antibodies that develop after an infection with one type don’t protect against infection with another type. Instead, the antibodies can actually help the second virus invade certain immune-system cells, where the virus readily replicates, making the infection worse. The phenomenon is called antibody-dependent enhancement (ADE), and it helps explain why more severe cases of dengue—including a very dangerous condition called dengue hemorrhagic fever—tend to happen when a patient catches a second type of dengue.
Scientists have wondered whether Zika virus, which is close enough to dengue to cloud the results of diagnostic tests that look for antibodies, might also be close enough to cause ADE. That could help explain why Zika, which has long been thought to cause only mild disease, has suddenly been blamed for causing much more severe symptoms in Brazil and elsewhere, including birth defects in babies infected in the womb and a temporary paralysis called Guillain-Barré syndrome.
The first support for that theory came from a paper posted on the preprint server bioRxiv in April. Sharon Isern and Scott Michael of Florida Gulf Coast University in Fort Myers and their colleagues reported that both lab-grown antibodies to dengue and blood serum from dengue patients (which contains antibodies) dramatically boosted the replication of Zika virus in cells in the lab.
Today, in a paper published online in Nature Immunology, an independent group at Imperial College London reports similar results, showing that a number of different antibodies to dengue virus react to Zika, but not strongly enough to neutralize the virus. Instead, when blood plasma from patients who had recovered from dengue was added to cell cultures infected with Zika, it increased the amount of virus in the cultures by as much as 100-fold.
The data are persuasive, says Ernesto Marques, a public health expert at the University of Pittsburgh in Pennsylvania. But clinical and epidemiology studies need to confirm that the effect plays a role in patients. There are cases of congenital Zika syndrome in babies and mothers that do not have antidengue antibodies, he notes, so although antidengue antibodies may increase the risk of a mother passing the virus to her fetus, the antibodies are not essential to cause birth defects. Studies that look for antibodies to dengue in Zika patients are complicated by the similarity of the viruses, notes Gavin Screaton, an immunologist at Imperial College London and an author on the Nature Immunology paper. “We desperately need” blood tests that can easily distinguish whether a patient has antibodies to dengue, Zika, or both, he says.
Even if the findings are confirmed, there's not much people who were previously infected with dengue can do to protect themselves except reduce the risk of mosquito bites, for instance by using repellent. But such precautions are already recommended for everyone in Zika-affected countries.