Moi Meng Ling, Ami Yasushi, Shirai Kenji, Lim Chang-Kweng, Suzaki Yuriko, Saito Yuka, Kitaura Kazutaka, Saijo Masayuki, Suzuki Ryuji, Kurane Ichiro, Takasaki Tomohiko
Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan; Division of Experimental Animal Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan; Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan; College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan; National Institute of Infectious Diseases, Tokyo, Japan.
Department of Virology 1, National Institute of Infectious Diseases, Tokyo, Japan; Division of Experimental Animal Research, National Institute of Infectious Diseases, Musashimurayama, Tokyo, Japan; Department of Rheumatology and Clinical Immunology, Clinical Research Center for Allergy and Rheumatology, Sagamihara National Hospital, National Hospital Organization, Kanagawa, Japan; College of Bioresource Sciences, Nihon University, Fujisawa, Kanagawa, Japan; National Institute of Infectious Diseases, Tokyo, Japan
Am J Trop Med Hyg. 2015 Feb;92(2):370-6. doi: 10.4269/ajtmh.14-0455. Epub 2014 Dec 29.
Infection with a dengue virus (DENV) serotype induces cross-reactive, weakly neutralizing antibodies to different dengue serotypes. It has been postulated that cross-reactive antibodies form a virus-antibody immune complex and enhance DENV infection of Fc gamma receptor (FcγR)-bearing cells. We determined whether infectious DENV-antibody immune complex is formed in vivo in marmosets after passive transfer of DENV-specific monoclonal antibody (mAb) and DENV inoculation and whether infectious DENV-antibody immune complex is detectable using FcγR-expressing cells. Marmosets showed that DENV-antibody immune complex was exclusively infectious to FcγR-expressing cells on days 2, 4, and 7 after passive transfer of each of the mAbs (mAb 4G2 and mAb 6B6C) and DENV inoculation. Although DENV-antibody immune complex was detected, contribution of the passively transferred antibody to overall viremia levels was limited in this study. The results indicate that DENV cross-reactive antibodies form DENV-antibody immune complex in vivo, which is infectious to FcγR-bearing cells but not FcγR-negative cells.
感染登革病毒(DENV)血清型会诱导产生针对不同登革血清型的交叉反应性、弱中和抗体。据推测,交叉反应性抗体形成病毒 - 抗体免疫复合物,并增强登革病毒对表达Fcγ受体(FcγR)细胞的感染。我们确定在将DENV特异性单克隆抗体(mAb)被动转移并接种DENV后,感染性DENV - 抗体免疫复合物是否在狨猴体内形成,以及是否能用表达FcγR的细胞检测到感染性DENV - 抗体免疫复合物。狨猴实验表明,在分别被动转移每种单克隆抗体(mAb 4G2和mAb 6B6C)并接种DENV后的第2天、第4天和第7天,DENV - 抗体免疫复合物仅对表达FcγR的细胞具有感染性。虽然检测到了DENV - DENV - 抗体免疫复合物,但在本研究中,被动转移的抗体对总体病毒血症水平的贡献有限。结果表明,DENV交叉反应性抗体在体内形成DENV - 抗体免疫复合物,该复合物对表达FcγR的细胞具有感染性,但对FcγR阴性细胞无感染性。