Impact of prior flavivirus immunity on Zika virus infection in rhesus macaques

Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotyp...

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Published in:	PLoS pathogens Vol. 13; no. 8; p. e1006487
Main Authors:	McCracken, Michael K, Gromowski, Gregory D, Friberg, Heather L, Lin, Xiaoxu, Abbink, Peter, De La Barrera, Rafael, Eckles, Kenneth H, Garver, Lindsey S, Boyd, Michael, Jetton, David, Barouch, Dan H, Wise, Matthew C, Lewis, Bridget S, Currier, Jeffrey R, Modjarrad, Kayvon, Milazzo, Mark, Liu, Michelle, Mullins, Anna B, Putnak, J Robert, Michael, Nelson L, Jarman, Richard G, Thomas, Stephen J
Format:	Journal Article
Language:	English
Published:	United States Public Library of Science 01-08-2017 Public Library of Science (PLoS)
Subjects:	Animals Antibodies Antibodies, Neutralizing - immunology Antibodies, Viral - immunology Antigen-antibody reactions Biology and life sciences Cell culture Comparative analysis Cross Reactions - immunology Cross-reactivity Dengue Dengue fever Enzyme-Linked Immunosorbent Assay Epidemics Fever Flavivirus - immunology Flavivirus Infections - immunology Flavivirus Infections - pathology Health aspects Immunity In vitro methods and tests Infections Kinetics Macaca mulatta Medicine and Health Sciences Neutralization Polymerase Chain Reaction Prevention Reaction kinetics Research and Analysis Methods Risk factors Vaccines Vector-borne diseases Viral diseases Viruses Yellow fever Zika virus Zika Virus - immunology Zika Virus Infection - immunology Zika Virus Infection - pathology Brazil United States United States > US Maryland Massachusetts
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Summary:	Studies have demonstrated cross-reactivity of anti-dengue virus (DENV) antibodies in human sera against Zika virus (ZIKV), promoting increased ZIKV infection in vitro. However, the correlation between in vitro and in vivo findings is not well characterized. Thus, we evaluated the impact of heterotypic flavivirus immunity on ZIKV titers in biofluids of rhesus macaques. Animals previously infected (≥420 days) with DENV2, DENV4, or yellow fever virus were compared to flavivirus-naïve animals following infection with a Brazilian ZIKV strain. Sera from DENV-immune macaques demonstrated cross-reactivity with ZIKV by antibody-binding and neutralization assays prior to ZIKV infection, and promoted increased ZIKV infection in cell culture assays. Despite these findings, no significant differences between flavivirus-naïve and immune animals were observed in viral titers, neutralizing antibody levels, or immune cell kinetics following ZIKV infection. These results indicate that prior infection with heterologous flaviviruses neither conferred protection nor increased observed ZIKV titers in this non-human primate ZIKV infection model.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 RGJ and SJT are co-senior authors. The authors have declared that no competing interests exist.
ISSN:	1553-7374 1553-7366 1553-7374
DOI:	10.1371/journal.ppat.1006487