{"id":295,"date":"2017-10-17T16:19:11","date_gmt":"2017-10-17T20:19:11","guid":{"rendered":"http:\/\/labs.icahn.mssm.edu\/lim-lab\/?p=295"},"modified":"2025-11-18T13:29:24","modified_gmt":"2025-11-18T18:29:24","slug":"the-scientist-anti-flavivirus-antibodies-enhance-zika-infection-in-mice","status":"publish","type":"post","link":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/2017\/10\/17\/the-scientist-anti-flavivirus-antibodies-enhance-zika-infection-in-mice\/","title":{"rendered":"The-Scientist: Anti-Flavivirus Antibodies Enhance Zika Infection in Mice"},"content":{"rendered":"

http:\/\/www.the-scientist.com\/?articles.view\/articleNo\/49031\/title\/Anti-Flavivirus-Antibodies-Enhance-Zika-Infection-in-Mice\/<\/a><\/p>\n

Researchers report evidence of antibody-dependent enhancement in a Zika-infected,<\/p>\n

immunocompromised mouse model.<\/p>\n

Written By Anna Azvolinsky<\/p>\n

Published Mar 30, 2017 (UTC)3<\/p>\n

A more-severe dengue virus infection can occur in an individual previously exposed to a different dengue virus serotype. Researchers theorize that this more-severe secondary infection occurs because circulating anti-dengue antibodies are cross-reactive, helping virions of a different viral serotype invade and replicate within hostcells. This phenomenon is known as antibody-dependent enhancement (ADE).<\/p>\n

Whether existing antibodies to dengue could enhance infection by another flavivirus, Zika, in humans remains an open question. However, researchers from the IcahnSchool of Medicine at Mount Sinai in New York City have now demonstrated that ADE occurs in immunocompromised mice infected with Zika. The team\u2019s results were published today (March 30) in Science.<\/p>\n

\u201cThis is an excellent piece of fundamental science addressing the question of antibody-dependent enhancement in mice,\u201d said Nelson Michael, an HIV researcherat the Walter Reed Army Institute of Research in Silver Spring, Maryland, whose team is developing a Zika vaccine.<\/p>\n

\u201cMost of the evidence of Zika enhancement that exists up to now is from in vitro experiments, while this paper looks at outcomes in mice,\u201d Isabel Rodr\u00edguez-Barraquer, an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, wrote in an email to The Scientist.<\/p>\n

Mount Sinai\u2019s Jean Lim, Florian Krammer, Adolfo Garcia-Sastre, and their colleagues collected plasma samples from more than 200 people who were previously infected with dengue or West Nile virus, a more distantly related flavivirus, and who tested positive for IgG antibodies against either pathogen. In vitro, these plasma samples bound to Zika envelope protein, whereas samples from people who did not test positive for antibodies against these flaviviruses did not. The researchers observed signs of ADE when they added the plasma samples to cultured human cells expressing the Fc cell surface receptor, but not when the interaction between the cells\u2019 Fc receptors and the antibodies were blocked. Depleting IgG antibodies from the plasma, the researchers did not see signs of enhanced infection. These experiments suggested that the IgG antibody-Fc receptor interaction is important or these cells to internalize the attached virions, which results in ADE.<\/p>\n

The team next injected immunocompromised mice\u2014deficient in the interferon innate immune response\u2014with pooled human plasma samples from dengue- exposed, West Nile-exposed, or control individuals. Infecting these animals with Zika, only around 21 percent of the mice that received dengue antibody\u2013positive plasma survived a week after infection, compared to 60 percent and 93 percent of the West Nile antibody\u2013positive and control plasma, respectively. The Zika-infected mice that had received dengue antibody\u2013positive plasma developed a higher fever,more severe limb paralysis, and weight loss compared to mice that received West Nile antibody\u2013positive plasma.<\/p>\n

\u201cThis is the first small animal model for ADE in which a clinical fever has been observed,\u201d Lim said. \u201cThis is a clinically relevant disease outcome that told us our model is a good one to study ADE.\u201d<\/p>\n

The team found that its in vivo results were concentration-dependent: higher concentrations of dengue-exposed plasma appeared to protect against Zika infection, while lower concentrations resulted in more-severe symptoms and decreased survival.<\/p>\n

For Michael Diamond, who studies mosquito-borne human pathogens at Washington University in St. Louis, the next question is whether ADE will also occur in fetuses exposed to maternal antibodies against dengue or other flaviviruses. Another key question, wrote Diamond in an email to The Scientist, would be whether ADE of Zika occurs if mice are first vaccinated against\u2014or infected with dengue\u2014and then challenged with Zika.<\/p>\n

Researchers involved in Zika virus vaccine development see these as informative mouse experiments that may or may not be relevant in humans. \u201cThis study doesn\u2019t considerably change how we plan to develop Zika vaccines,\u201d said Stephen Thomas, chief of the division of infectious diseases at the State University of New York Upstate Medical University. \u201cThe message is that theories of immune enhancement need to be prospectively studied in humans.\u201d<\/p>\n

The next step is to complete ongoing epidemiological studies to determine whether Zika infection is enhanced in people who had been previously infected with another flavivirus, noted Michael. \u201cThen we can go back to the animal models and ask which one was most predictive of what we saw in people. And that\u2019s where we\u2019re heading pretty quickly.\u201d<\/p>\n

Rodriguez-Barraquer agreed. \u201cSince experiments like the ones in this paper can\u2019t be conducted in humans directly,\u201d she wrote, \u201ccareful analysis of new and existing epidemiological data around the world are needed to gain understanding of whetherZika enhancement by dengue antibodies is relevant in human populations.\u201d<\/p>\n

S.V. Bardina et al., \u201cEnhancement of Zika virus pathogenesis by pre-existing antiflavivirus immunity,\u201d Science, doi:10.1126\/science.aal4365, 2017.<\/p>\n

https:\/\/www.the-scientist.com<\/p>\n

\u00a9 1986 \u2013 !2025 THE SCIENTIST. ALL RIGHTS RESERVED.<\/p>\n

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http:\/\/www.the-scientist.com\/?articles.view\/articleNo\/49031\/title\/Anti-Flavivirus-Antibodies-Enhance-Zika-Infection-in-Mice\/ Researchers report evidence of antibody-dependent enhancement in a Zika-infected, immunocompromised mouse model. Written By Anna Azvolinsky Published Mar 30, 2017 (UTC)3 A more-severe dengue virus infection can occur in an individual previously exposed to a different dengue virus serotype. Researchers theorize that this more-severe secondary infection occurs because circulating anti-dengue antibodies are cross-reactive, helping […]<\/p>\n","protected":false},"author":121,"featured_media":0,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_et_pb_use_builder":"","_et_pb_old_content":"","_et_gb_content_width":"","footnotes":""},"categories":[1],"tags":[],"class_list":["post-295","post","type-post","status-publish","format-standard","hentry","category-press-2"],"aioseo_notices":[],"_links":{"self":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts\/295","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/users\/121"}],"replies":[{"embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/comments?post=295"}],"version-history":[{"count":5,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts\/295\/revisions"}],"predecessor-version":[{"id":1395,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/posts\/295\/revisions\/1395"}],"wp:attachment":[{"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/media?parent=295"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/categories?post=295"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/labs.icahn.mssm.edu\/lim-lab\/wp-json\/wp\/v2\/tags?post=295"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}