Jagodzinski P P, Wustner J, Kmieciak D, Wasik T J, Fertala A, Sieron A L, Takahashi M, Tsuji T, Mimura T, Fung M S, Gorny M K, Kloczewiak M, Kaneko Y, Kozbor D
Department of Microbiology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
Virology. 1996 Dec 15;226(2):217-27. doi: 10.1006/viro.1996.0649.
A sulfated polysaccharide, curdlan sulfate (CRDS) with 1,3-beta-D-glucan as a main chain, inhibits HIV-1 infection of human peripheral blood lymphocytes (PBLs) by binding to the V3 region of gp 120. We previously showed that T cell (T)-tropic HIV-1 isolates are over 10-fold more sensitive to neutralization by CRDS than macrophage (MT)-tropic viruses, which possesses a relatively less charged amino acid composition in the V3 sequence. To analyze the interaction of CRDS with V3 and its association with neutralization sensitivity of HIV-1 isolates, we examined the effect of CRDS on the binding of neutralizing antibodies to monomeric and oligomeric gp 120 mutants of T- and MT-tropic HIV-1 clones in which the V3 loop was either deleted or substituted by V3 of another isolate. Our results showed that the presence and the amino acid composition of the V3 loop appears to determine the extent of interaction of CRDS with the V2 and CD4-binding regions on native gp 120 monomers; however, the positive charge of V3 has less effect on this interaction on oligomeric gp 120. Furthermore, our results established that only the CRDS-induced masking of V3 on oligomeric gp120 appears to be associated with the anti-HIV-1 activity of CRDS in vitro. Our findings underline the usefulness of CRDS for understanding the structural constraints on gp 120 that drive the transition from MT- to T-tropic isolates in vivo and enable the virus to use multiple fusion cofactors.
一种以1,3-β-D-葡聚糖为主链的硫酸化多糖——硫酸凝胶多糖（CRDS），通过与gp 120的V3区域结合来抑制HIV-1对人外周血淋巴细胞（PBL）的感染。我们之前表明，T细胞嗜性的HIV-1分离株对CRDS中和作用的敏感性比巨噬细胞嗜性病毒高10倍以上，后者在V3序列中具有相对电荷较少的氨基酸组成。为了分析CRDS与V3的相互作用及其与HIV-1分离株中和敏感性的关联，我们检测了CRDS对中和抗体与T细胞嗜性和巨噬细胞嗜性HIV-1克隆的单体和寡聚体gp 120突变体结合的影响，这些突变体的V3环要么被删除，要么被另一个分离株的V3取代。我们的结果表明，V3环的存在和氨基酸组成似乎决定了CRDS与天然gp 120单体上的V2和CD4结合区域的相互作用程度；然而，V3的正电荷对寡聚体gp 120上这种相互作用的影响较小。此外，我们的结果表明，只有CRDS诱导的寡聚体gp120上V3的掩盖似乎与CRDS在体外的抗HIV-1活性相关。我们的发现强调了CRDS对于理解gp 120的结构限制的有用性，这些限制驱动了体内从巨噬细胞嗜性分离株向T细胞嗜性分离株的转变，并使病毒能够使用多种融合辅助因子。
