Dengue immune sera enhance Zika virus infection in human peripheral blood monocytes through Fc gamma receptors

• Published in: PloS one Vol. 13; no. 7; p. e0200478
• Main Authors: Li, Min, Zhao, Lingzhai, Zhang, Chao, Wang, Xin, Hong, Wenxin, Sun, Jin, Liu, Ran, Yu, Lei, Wang, Jianhua, Zhang, Fuchun, Jin, Xia
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 25.07.2018; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Antibodies; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antibody-Dependent Enhancement - immunology; Antisera; Biology and Life Sciences; Blood; CD14 antigen; CD16 antigen; Cross Reactions - immunology; Dendritic cells; Dendritic Cells - immunology; Dengue; Dengue - blood; Dengue - immunology; Dengue - virology; Dengue fever; Dengue virus; Dengue Virus - immunology; Fc receptors; Female; Glycoproteins; Guillain-Barre syndrome; Humans; Immune Sera - immunology; Immune serum; Immunoglobulins; Immunology; Infections; Infectivity; Laboratories; Leukemia; Leukocytes (mononuclear); Lymphocytes; Lymphocytes B; Lymphocytes T; Male; Medicine and Health Sciences; Microcephaly; Middle Aged; Monocytes; Monocytes - immunology; Neutralization; Neutralization Tests; Pathogenesis; Peripheral blood mononuclear cells; Receptors; Receptors, IgG - blood; Receptors, IgG - immunology; Research and Analysis Methods; Tumor cell lines; Vector-borne diseases; Viral diseases; Virology; Viruses; Young Adult; Zika virus; Zika Virus - immunology; Zika Virus - pathogenicity; Zika virus infection; Zika Virus Infection - immunology; Zika Virus Infection - virology; Brazil; Beijing China; China; French Polynesia
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0200478

Antibody dependent enhancement (ADE) has most often been associated with dengue virus (DENV). Studies using leukemia cell lines suggest that DENV specific antibodies can enhance Zika virus (ZIKV) infectivity, and vice versa. To examine the mechanisms of ADE of ZIKV infection in primary human cells, we assessed 40 serum samples obtained from convalescent DENV-1 or DENV-3 infected subjects. All sera tested exhibited high binding potency, while modest or none neutralization activities against ZIKV. Primary CD14+ monocytes, rather than B and T cells in peripheral blood mononuclear cells (PBMCs), were found to be the mediators of the enhancement of ZIKV infectivity by DENV immune sera. Monocyte-derived immature dendritic cells (DCs), but not mature DCs were highly permissive to ZIKV infection, whereas neither immature nor mature DCs could mediate enhanced ZIKV infection in the presence of DENV immune sera. In addition, antibody blocking of either FcγRI (CD64), or FcγRII (CD32), or FcγRIII (CD16) resulted in diminished ADE of ZIKV infection. Our findings provide an improved understanding of the pathogenesis of ZIKV infection, and inform rational vaccine design.