T-Tropic Human Immunodeficiency Virus Type 1 (HIV-1)-Derived V3 Loop Peptides Directly Bind to CXCR-4 and Inhibit T-Tropic HIV-1 Infection
T-Tropic Human Immunodeficiency Virus Type 1 (HIV-1)-Derived V3 Loop Peptides Directly Bind to CXCR-4 and Inhibit T-Tropic HIV-1 Infection
复制标题
T-Tropic 人类免疫缺陷病毒 1 型 (HIV-1) 衍生的 V3 环肽直接结合 CXCR-4 并抑制 T-Tropic HIV-1 感染
作者：
H. Sakaida;Toshiyuki Hori;Akihito Yonezawa;A. Sato;Y. Isaka;O. Yoshie;T. Hattori;T. Uchiyama
某些类型的趋化因子受体已被鉴定为HIV-1感染的辅助受体。病毒进入的过程是由HIV-1的包膜蛋白gp 120、CD 4和相关辅助受体之一之间的相互作用启动的。为了理解Env介导的HIV-1融合和进入的精确机制，我们检测了T细胞系嗜性T细胞系gp 120的V3区是否与HIV-1的融合和进入有关。（嗜T）病毒通过使用五种合成的V3肽与辅助受体CXCR-4直接相互作用：两个环化V3肽（V3-BH 10和V3-ELI），其分别对应于T嗜性HIV-1 IIIB和HIV-1 ELI毒株的V3区，对应于HIV-1 IIIB株的线性V3肽（CTR 36）;和对应于嗜巨噬细胞（M-嗜性）HIV-1 ADA株（V3-ADA）或双嗜性HIV-1 89.6株（V3-89.6）的环状V3肽。采用CXCR-4+人B细胞系JY进行的FACScan分析显示，V3-BH 10、V3-ELI和V3-89.6（而非CTR 36或V3-ADA）以剂量依赖性方式以不同程度阻断IVR 7（一种抗CXCR-4单克隆抗体（MAb））与CXCR-4的结合，而V3肽根本不影响抗CD 19 MAb的结合。接下来，研究了V3肽对SDF-1β诱导的细胞内Ca 2+瞬时增加的影响。三种V3肽（V3-BH 10、V3-ELI和V3-89.6）阻止Ca 2+动员。此外，三种肽抑制T嗜性HIV-1感染的剂量依赖性的方式所揭示的MTT法和逆转录酶测定，而其他肽没有效果。这些结果提供了直接的证据，T嗜性HIV-1的gp 120的V3环可以与其辅助受体CXCR-4相互作用，而不依赖于gp 120或细胞CD 4的V1/V2区。
ABSTRACT Certain types of chemokine receptors have been identified as coreceptors for HIV-1 infection. The process of viral entry is initiated by the interaction between an envelope protein gp120 of HIV-1, CD4, and one of the relevant coreceptors. To understand the precise mechanism of the Env-mediated fusion and entry of HIV-1, we examined whether the V3 region of gp120 of T-cell line tropic (T-tropic) virus directly interacts with the coreceptor, CXCR-4, by using five synthetic V3 peptides: two cyclized V3 peptides (V3-BH10 and V3-ELI) which correspond to the V3 regions of the T-tropic HIV-1 IIIB and HIV-1 ELI strains, respectively, a linear V3 peptide (CTR36) corresponding to that of HIV-1 IIIB strain; and cyclized V3 peptides corresponding to that of the macrophage-tropic (M-tropic) HIV-1 ADA strain (V3-ADA) or the dualtropic HIV-1 89.6 strain (V3-89.6). FACScan analysis with a CXCR-4+ human B-cell line, JY, showed that V3-BH10, V3-ELI, and V3-89.6 but not CTR36 or V3-ADA blocked the binding of IVR7, an anti-CXCR-4 monoclonal antibody (MAb), to CXCR-4 with different magnitudes in a dose-dependent manner, while none of the V3 peptides influenced binding of an anti-CD19 MAb at all. Next, the effects of the V3 peptides on SDF-1β-induced transient increases in intracellular Ca2+ were investigated. Three V3 peptides (V3-BH10, V3-ELI, and V3-89.6) prevented Ca2+mobilization. Furthermore, the three peptides inhibited infection by T-tropic HIV-1 in a dose-dependent manner as revealed by an MTT assay and a reverse transcriptase assay, while the other peptides had no effects. These results present direct evidence that the V3 loop of gp120 of T-tropic HIV-1 can interact with its coreceptor CXCR-4 independently of the V1/V2 regions of gp120 or cellular CD4.
V2 结构域内的微小氨基酸序列变化可影响 T 细胞系嗜性人类免疫缺陷病毒 1 型包膜 gp120 的功能。
DOI：
10.1006/viro.1995.1010
发表时间：
1995
期刊：
Virology.
影响因子：
--
作者：
Koito,A;Stamatatos,L;Cheng-Mayer,C
通讯作者：
Cheng-Mayer,C
影响因子：
22.1
作者：
Berberidou, Chrysanthi;Kitsiou, Vasiliki;Poulios, Ioannis
通讯作者：
Poulios, Ioannis
影响因子：
56.9
作者：
Rizzuto, CD;Wyatt, R;Sodroski, J
通讯作者：
Sodroski, J