Lok S M, Ng M L, Aaskov J
School of Life Sciences, Queensland University of Technology, Brisbane, Australia.
J Med Virol. 2001 Oct;65(2):315-23. doi: 10.1002/jmv.2036.
Two dengue 2-specific IgM monoclonal antibodies (MAb) recognised spatially unrelated epitopes on the envelope (E) protein of dengue 2 virus, which were also recognised by serum from 20 and 50%, respectively, of patients with a primary dengue 2 infection. Dengue 2 virus populations escaping neutralisation by MAb 6B2 (representing the majority population of dengue 2-specific IgM MAbs ) had a deduced amino acid change (G-S) in the pre-Membrane (prM) protein at position 15 and a second in the E protein at E311 (E-G). The change in the E protein was adjacent to the only other epitopes on dengue 2 virus (E307, E383-385) involved in neutralisation that have been identified but that were recognised by IgG antibodies. Dengue 2 virus escaping neutralisation by IgM MAb 10F2, representing the minority population of dengue 2-specific IgM MAbs, had the same deduced amino acid change (G-S) at prM15 as the 6B2 neutralisation escape mutant dengue 2 virus population and four deduced amino acid changes in the E protein (E69, T-I, in the glycosylation motif; E71, E-D; E112, S-G; E124, I-N), which may be close enough to each other to form a single epitope and a fifth at E402 (F-L) in a region of the E protein of TBE virus essential for the low pH-induced E protein dimer-trimer transition. The 10F2 neutralisation escape mutant, but not the 6B2 one, had lost its ability to cause fusion from within Aedes albopictus mosquito cells and was inactivated more rapidly than the 6B2 neutralisation escape mutant and wild type viruses at 42 degrees C. Dengue 2 viruses passaged in BHK cells in the absence of a selecting antibody, shared a common amino acid (S) at E53, which differed from both wild type and neutralisation escape mutant virus populations at this position (P) and may have been responsible for a significant reduction in the ability of these "passage control" virus populations to be neutralised by both 6B2 and 10F2 antibodies.
两种登革2型特异性IgM单克隆抗体（MAb）识别登革2型病毒包膜（E）蛋白上空间不相关的表位，在初次感染登革2型病毒的患者血清中，分别有20%和50%的血清也能识别这些表位。逃避MAb 6B2（代表登革2型特异性IgM MAb的主要群体）中和作用的登革2型病毒群体，其膜前（prM）蛋白第15位有一个推导氨基酸变化（G-S），E蛋白的E311位有第二个变化（E-G）。E蛋白的变化与登革2型病毒上唯一其他参与中和作用的表位（E307、E383 - 385）相邻，这些表位已被鉴定，但由IgG抗体识别。逃避代表登革2型特异性IgM MAb少数群体的IgM MAb 10F2中和作用的登革2型病毒，在prM15位有与6B2中和逃逸突变登革2型病毒群体相同的推导氨基酸变化（G-S），E蛋白有四个推导氨基酸变化（糖基化基序中的E69，T-I；E71，E-D；E112，S-G；E124，I-N）或许彼此足够接近以形成一个单一表位，在E蛋白的一个区域（TBE病毒E蛋白低pH诱导的二聚体-三聚体转变所必需）的E402位有第五个变化（F-L）。10F2中和逃逸突变体，但不是6B2中和逃逸突变体，失去了在白纹伊蚊细胞内引发融合的能力，并且在42℃时比6B2中和逃逸突变体和野生型病毒更快失活。在没有选择抗体的情况下在BHK细胞中传代的登革2型病毒，在E53位有一个共同氨基酸（S），该位置与野生型和中和逃逸突变病毒群体在此位置的氨基酸（P）不同，这可能导致这些“传代对照”病毒群体被6B2和10F2抗体中和的能力显著降低。
