Dengue Antibodies appear to enhance Zika Infection – April 2016

Dengue Antibodies Enhance Zika Infection? TheScientist

Previous flavivirus infection could help explain the severity of symptoms in some people infected during the ongoing Zika outbreak, researchers report.
By Tanya Lewis | April 28, 2016
CDC; Frederick Murphy, Cynthia Goldsmith

Scientists at Florida Gulf Coast University and their colleagues have found that human cells were more likely to be infected with Zika virus in vitro if they contained antibodies to dengue virus. Their findings, detailed Monday (April 25) in a bioRxiv preprint, could help explain why Zika infection appears to be more severe in areas where dengue is endemic, and points to a potential unintended effect of dengue vaccination.

Antibodies to dengue can increase the virus’s infectivity for certain types of immune cells through a process called antibody-dependent enhancement (ADE), resulting in the production of more virus and more severe illness. (See “Antibody-Dependent Enhanced (ADE) Immunity,” The Scientist, May 2013.) For the present study, the researchers cultured cells with immune proteins called Fc receptors and exposed them to Zika virus in the presence of human monoclonal antibodies to dengue, finding that Zika virus infection increased 100-fold.

The researchers also exposed the cells to Zika in the presence of serum from four patients who had recovered from dengue, finding that all four sera enhanced Zika virus infection. Blocking these Fc receptors negated the effect, the team found.

The study measured enhancement of Zika infection by PCR amplification of the infected cells’ RNA, rather than measuring the actual amount of virus produced, Vincent Racaniello of Columbia University, who was not involved in the study, wrote on his blog, noting one limitation of their investigation.

The findings, which have yet to be confirmed in vivo, raise concerns about the use of Dengvaxia, a dengue vaccine recently approved for use in Brazil, Mexico, and the Philippines, Racaniello wrote.

  Download the bioRxiv preprint from VitaminDWiki

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Many interesting charts
I cannot figure out what they mean yet.

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Antibody-dependent enhancement" on the web

• ADE Dengue Nature 2007
  
• https://en.wikipedia.org/wiki/Antibody-dependent_enhancement
  "The most widely known example of ADE occurs in the setting of infection with the dengue virus"
  "The phenomenon of ADE may be observed when a person who has previously been infected with one serotype of DENV becomes infected many months or years later with a different serotype"
• http://www.denguevirusnet.com/antibody-dependent-enhancement.html

Antibody-dependent enhancement" and ZIKA on the web

• Dengue could be the surprise culprit making Zika worse, researchers say Feb 2016
  "The theory — and it’s only that right now — is that prior infection with one or more of the four dengue viruses may be contributing to a spike in Brazil’s cases of neurological complications among some adults infected with Zika and cases of microcephaly — underdeveloped heads and brains — in some infants born to women infected with the virus during pregnancy."
  "He outlined how this still-hypothetical scenario might work: Women with antibodies to dengue viruses might develop higher levels of virus in the blood if they contract Zika virus. Those higher levels of virus in the blood might allow Zika to occasionally cross the placenta into the fetus, and trigger infection that damages its developing brain."
  "If the theory about dengue compounding Zika’s side effects turns out to be true, it will be good news for places — such as most of the continental US — where dengue viruses have not circulated. It would mean the risk posed by Zika might be lower than currently expected."
• Lab findings hint that dengue antibodies intensify Zika infection April 26
  Center for Infectous Disease Research and Policy reporting on the study on this page
• Antibodies to dengue virus enhance infection by Zika virus Virology Blog April 27
  "It will be important to confirm these findings in animal models of Zika virus infection, and in humans. If true, they have wide implications. If antibodies against dengue virus enhance Zika virus infection in humans, more severe disease might be observed in areas such as Brazil where both viruses co-circulate."
  "It is also possible that antibodies to Zika virus might enhance dengue virus disease."
  "These observations do not bode well for Dengvaxia, a tetravalent dengue virus vaccine that has been recently licensed in Brazil, Mexico, and the Philippines. Might anti-dengue virus antibodies induced by this vaccine make Zika virus disease more severe? "
  A comment on the blog post "Any dengue antibody will enhance dengue virus at some dilution. Moreover, dengue antibodies can enhance West Nile, Japanese Encephalitis and Yellow fever virus infection of Fc receptor bearing cells. The reverse is true as well-i.e. JE, WN and YF antibodies can enhance dengue. A flavivirus vaccine serum sample will enhance dengue or another flavivirus at some dilution. Therefore, it is expected that dengue antibodies will enhance Zika. The challenge for the field is to understand antibody virus interactions that may lead to virus and disease enhancement in people. Current models do not accurately predict this."