Probing the interaction between feline immunodeficiency virus and CD134 by using the novel monoclonal antibody 7D6 and the CD134 (Ox40) ligand.
Probing the interaction between feline immunodeficiency virus and CD134 by using the novel monoclonal antibody 7D6 and the CD134 (Ox40) ligand.
复制标题
使用新型单克隆抗体 7D6 和 CD134 (Ox40) 配体探讨猫免疫缺陷病毒与 CD134 之间的相互作用。
DOI：
10.1128/jvi.01020-07
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发表时间：
2007
影响因子：
5.4
通讯作者：
Hosie,MargaretJ
中科院分区：
文献类型：
--
作者：
Willett,BrianJ;McMonagle,ElizabethL;Logan,Nicola;Spiller,OBrad;Schneider,Pascal;Hosie,MargaretJ
猫免疫缺陷病毒（FIV）优先靶向活化的CD4阳性辅助性T细胞，在其天然宿主物种家猫中诱导AIDS样免疫缺陷。FIV的主要受体是CD134，肿瘤坏死因子受体超家族的成员，并且迄今为止测试的所有主要病毒株使用CD134进行感染。我们使用一种新型抗猫CD 134单克隆抗体（MAb）7D6检测了猫中CD 134的表达，结果表明，与大鼠和人类一样，CD 134的表达严格限于CD 4 + T细胞，而不是CD 8 + T细胞，这与FIV选择性靶向这些细胞一致。然而，FIV也是嗜巨噬细胞的，并且在慢性感染中病毒嗜性扩大到包括B细胞和CD8+T细胞。使用7D6，我们揭示了B220阳性（B细胞）群体和培养的巨噬细胞上的CD 134表达，但不是外周血单核细胞。此外，巨噬细胞CD134的表达和FIV感染增强激活响应细菌脂多糖。与人和鼠T细胞上的CD 134表达一致，猫CD 134在有丝分裂原刺激的CD 4 +T细胞上丰富，在CD 8 +T细胞上表达较弱，这与FIV随着感染进展扩增至CD 8 +T细胞一致。使用MAb 7D6和可溶性CD134配体（CD134L）探测FIV和CD134之间的相互作用，揭示了对7D6和CD134L敏感性的菌株特异性差异。7D6和CD134L均能很好地抑制PPR和B2542等分离株的感染，表明相互作用的亲和力较低。相反，GL8、CPG和NCSU对7D6和CD134L的抑制相对难治，因此可能与CD134具有更高的亲和力相互作用，允许感染CD134水平有限的细胞。
The feline immunodeficiency virus (FIV) targets activated CD4-positive helper T cells preferentially, inducing an AIDS-like immunodeficiency in its natural host species, the domestic cat. The primary receptor for FIV is CD134, a member of the tumor necrosis factor receptor superfamily, and all primary viral strains tested to date use CD134 for infection. We examined the expression of CD134 in the cat using a novel anti-feline CD134 monoclonal antibody (MAb), 7D6, and showed that as in rats and humans, CD134 expression is restricted tightly to CD4+, and not CD8+, T cells, consistent with the selective targeting of these cells by FIV. However, FIV is also macrophage tropic, and in chronic infection the viral tropism broadens to include B cells and CD8+T cells. Using 7D6, we revealed CD134 expression on a B220-positive (B-cell) population and on cultured macrophages but not peripheral blood monocytes. Moreover, macrophage CD134 expression and FIV infection were enhanced by activation in response to bacterial lipopolysaccharide. Consistent with CD134 expression on human and murine T cells, feline CD134 was abundant on mitogen-stimulated CD4+T cells, with weaker expression on CD8+T cells, concordant with the expansion of FIV into CD8+T cells with progression of the infection. The interaction between FIV and CD134 was probed using MAb 7D6 and soluble CD134 ligand (CD134L), revealing strain-specific differences in sensitivity to both 7D6 and CD134L. Infection with isolates such as PPR and B2542 was inhibited well by both 7D6 and CD134L, suggesting a lower affinity of interaction. In contrast, GL8, CPG, and NCSU were relatively refractory to inhibition by both 7D6 and CD134L and, accordingly, may have a higher-affinity interaction with CD134, permitting infection of cells where CD134 levels are limiting.