In the Journals

Past dengue exposure may increase potency of Zika infection

New research suggests that the potency of a Zika virus infection may be greater in patients who were previously exposed to dengue virus — a link that may explain the extent of the current outbreak of Zika in the Americas.

In these patients, Zika’s effect can be amplified through the same process — antibody-dependent enhancement (ADE) — that makes a second dengue infection often more serious that the first, according to research published in Nature Immunology.

“This may be why the current outbreak has been so severe, and why it has been in areas where dengue is prevalent,” Gavin R. Screaton, MRCP, DPhil, dean of the faculty of medicine at Imperial College London, said in a news release. “We now need further studies to confirm these findings, and to progress toward a vaccine.”

Research comes amid outbreak

Zika and dengue viruses share a common vector, the Aedes mosquito, and circulate in the same areas of Brazil. Further, they are both flaviviruses. While dengue has been known to cause severe headache and pain in the muscles and joints, however, Zika virus had been associated with milder symptoms until the current outbreak. Now, it has been shown to cause microcephaly and other serious birth defects in infants, and has been linked to Guillain-Barré syndrome in adults.

Global infections of dengue are thought to be around 390 million per year. The virus is common in South America; in some areas also affected by Zika, the seroprevalence of dengue exceeds 90%, according to Screaton and colleagues.

They started their study by collecting monoclonal antibodies from dengue-infected patients and adding them to human cell cultures along with Zika virus. They found that plasma containing antibodies to dengue virus “substantially cross-reacted” with Zika.

Next, the researchers discovered that pre-existing dengue antibodies could amplify Zika through ADE — the phenomenon in which antibodies are imperfectly matched with invading bacteria or viruses, which break off when they are shuttled to an immune cell and end up causing an infection. This is thought to be why a second infection with dengue virus, which has four types, is often worse that the first infection — and, now, why Zika may replicate more easily in patients who have previously been exposed to dengue.

The two findings highlight the similarities between the viruses, Screaton and colleagues concluded.

“In this context,” they wrote, “Zika virus could be considered a fifth member of the dengue virus serocomplex, a factor that must be considered in vaccine approaches to these two viruses.”

Working toward a vaccine

In a second study, the same group of researchers confirmed that EDE1 antibodies, which work to prevent ADE, bind efficiently to Zika virus and can potentially neutralize infection. Screaton and colleagues believe the discovery could provide a pathway to a universal vaccine that protects against dengue and Zika simultaneously.

“These new studies suggest that prior infection with dengue doesn’t offer any protection against Zika, and may in fact predispose people to a more severe infection. We can’t say yet whether this interaction is playing a role in the current outbreak, but if confirmed it’s likely to have important implications for the control and global spread of Zika, and for the development of any vaccine for the virus,” Jeremy Farrar, FMedSci, FRS, OBE, director of the Wellcome Trust, a supporter of the research, said in the news release.

“There are still more questions than answers about Zika and this group of viruses including dengue. We know that Zika has been present in Southeast Asia and Africa for many years and yet has not taken off there as it has in South America. This is what the international research effort needs to work out, and quickly.” – by Gerard Gallagher

Disclosures: Screaton reports being named as an inventor on a patent related to this work. Farrar is director of the Wellcome Trust. Please see the full studies for a list of all other authors’ relevant financial disclosures.

New research suggests that the potency of a Zika virus infection may be greater in patients who were previously exposed to dengue virus — a link that may explain the extent of the current outbreak of Zika in the Americas.

In these patients, Zika’s effect can be amplified through the same process — antibody-dependent enhancement (ADE) — that makes a second dengue infection often more serious that the first, according to research published in Nature Immunology.

“This may be why the current outbreak has been so severe, and why it has been in areas where dengue is prevalent,” Gavin R. Screaton, MRCP, DPhil, dean of the faculty of medicine at Imperial College London, said in a news release. “We now need further studies to confirm these findings, and to progress toward a vaccine.”

Research comes amid outbreak

Zika and dengue viruses share a common vector, the Aedes mosquito, and circulate in the same areas of Brazil. Further, they are both flaviviruses. While dengue has been known to cause severe headache and pain in the muscles and joints, however, Zika virus had been associated with milder symptoms until the current outbreak. Now, it has been shown to cause microcephaly and other serious birth defects in infants, and has been linked to Guillain-Barré syndrome in adults.

Global infections of dengue are thought to be around 390 million per year. The virus is common in South America; in some areas also affected by Zika, the seroprevalence of dengue exceeds 90%, according to Screaton and colleagues.

They started their study by collecting monoclonal antibodies from dengue-infected patients and adding them to human cell cultures along with Zika virus. They found that plasma containing antibodies to dengue virus “substantially cross-reacted” with Zika.

Next, the researchers discovered that pre-existing dengue antibodies could amplify Zika through ADE — the phenomenon in which antibodies are imperfectly matched with invading bacteria or viruses, which break off when they are shuttled to an immune cell and end up causing an infection. This is thought to be why a second infection with dengue virus, which has four types, is often worse that the first infection — and, now, why Zika may replicate more easily in patients who have previously been exposed to dengue.

The two findings highlight the similarities between the viruses, Screaton and colleagues concluded.

“In this context,” they wrote, “Zika virus could be considered a fifth member of the dengue virus serocomplex, a factor that must be considered in vaccine approaches to these two viruses.”

Working toward a vaccine

In a second study, the same group of researchers confirmed that EDE1 antibodies, which work to prevent ADE, bind efficiently to Zika virus and can potentially neutralize infection. Screaton and colleagues believe the discovery could provide a pathway to a universal vaccine that protects against dengue and Zika simultaneously.

“These new studies suggest that prior infection with dengue doesn’t offer any protection against Zika, and may in fact predispose people to a more severe infection. We can’t say yet whether this interaction is playing a role in the current outbreak, but if confirmed it’s likely to have important implications for the control and global spread of Zika, and for the development of any vaccine for the virus,” Jeremy Farrar, FMedSci, FRS, OBE, director of the Wellcome Trust, a supporter of the research, said in the news release.

“There are still more questions than answers about Zika and this group of viruses including dengue. We know that Zika has been present in Southeast Asia and Africa for many years and yet has not taken off there as it has in South America. This is what the international research effort needs to work out, and quickly.” – by Gerard Gallagher

Disclosures: Screaton reports being named as an inventor on a patent related to this work. Farrar is director of the Wellcome Trust. Please see the full studies for a list of all other authors’ relevant financial disclosures.

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