title: Human parvovirus B19 antibodies induce altered membrane protein expression and apoptosis of BeWo trophoblasts.
abstract: Human parvovirus B19 (B19) is harmful during pregnancy since it can be vertically transmitted to the developing fetus. In addition, the anti‑B19 antibodies induced by B19 infection are believed to have a cytopathic role in B19 transmission; however, knowledge regarding the effects of anti‑B19 antibodies during pregnancy is limited. To investigate the possible roles of anti‑B19 antibodies during pregnancy, the present study examined the effects of anti‑B19‑VP1 unique region (VP1u), anti‑B19‑VP2 and anti‑B19‑nonstructural protein 1 (NS1) immunoglobulin G (IgG) antibodies on BeWo trophoblasts. Briefly, BeWo trophoblasts were incubated with purified IgG against B19‑VP1u, B19‑VP2 and B19‑NS1. Subsequently, the expression of surface proteins and apoptotic molecules were assessed in BeWo trophoblasts using flow cytometry, ELISA and western blotting. The expression levels of human leukocyte antigen (HLA)‑G were significantly increased on BeWo trophoblasts treated with rabbit anti‑B19‑VP1u IgG, and were unchanged in those treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, as compared with the control group. Furthermore, the expression levels of globoside (P blood group antigen) and cluster of differentiation (CD)29 (β1 integrin) were significantly increased in BeWo trophoblasts treated with rabbit anti‑B19‑NS1 and anti‑B19‑VP2 IgG, whereas only CD29 was also significantly increased in cells treated with anti‑B19‑VP1u IgG. In addition, the number of cells at sub‑G1 phase; caspase‑3 activity; and the expression of intrinsic and extrinsic apoptotic molecules, including Fas‑associated death domain protein, activated caspase‑8, activated caspase‑3, B‑cell lymphoma 2‑associated X protein, cytochrome c, apoptotic peptidase activating factor 1 and activated caspase‑9, were significantly increased in BeWo trophoblasts treated with anti‑B19‑VP1u and anti‑B19‑NS1 IgG. In conclusion, the present study demonstrated that antibodies against B19 may have a crucial role in pathological processes during pregnancy. These findings may help to elucidate the mechanisms underlying transmission of the B19 virus during pregnancy.
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
authors.forename: Bor-Show
authors.initials: BS
authors.lastname: Tzang
authors.affiliation: Division of Neurology, Department of Internal Medicine, Chi Mei Medical Center, Liouying 73663, Taiwan, R.O.C.
authors.forename: Szu-Yi
authors.initials: SY
authors.lastname: Chiang
authors.affiliation: Department of Biochemistry, School of Medicine, China Medical University, Taichung 40402, Taiwan, R.O.C.
authors.forename: Hsu-Chin
authors.initials: HC
authors.lastname: Chan
authors.affiliation: Department of Obstetrics and Gynecology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung 40201, Taiwan, R.O.C.
authors.forename: Chung-Hsien
authors.initials: CH
authors.lastname: Liu
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan, R.O.C.
authors.forename: Tsai-Ching
authors.initials: TC
authors.lastname: Hsu
mesh_terms: D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000008:administration & dosage / Q000276:immunology; D000914:Antibodies, Viral / Q000276:immunology* / Q000302:isolation & purification; D017209:Apoptosis / Q000276:immunology; D036022:Capsid Proteins / Q000037:antagonists & inhibitors / Q000276:immunology; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D010322:Parvoviridae Infections / Q000276:immunology* / Q000635:transmission / Q000821:virology; D016732:Parvovirus B19, Human / Q000276:immunology* / Q000302:isolation & purification / Q000472:pathogenicity; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology* / Q000628:therapy / Q000821:virology; D011817:Rabbits; D014327:Trophoblasts / Q000276:immunology* / Q000821:virology; D017361:Viral Nonstructural Proteins / Q000037:antagonists & inhibitors / Q000276:immunology
chemical_list: D000888:Antibodies, Anti-Idiotypic; D000914:Antibodies, Viral; D036022:Capsid Proteins; D007074:Immunoglobulin G; D008565:Membrane Proteins; C106202:NS1 protein, parvovirus; D017361:Viral Nonstructural Proteins; C095547:capsid protein VP1, parvovirus B19; C095548:capsid protein VP2, parvovirus B19