Induction of Rod-Shaped Structures by Herpes Simplex Virus Glycoprotein I
Induction of Rod-Shaped Structures by Herpes Simplex Virus Glycoprotein I
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单纯疱疹病毒糖蛋白 I 诱导棒状结构
DOI：
10.1128/jvi.00231-20
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发表时间：
2020-06
影响因子：
5.4
通讯作者：
Yang Hanchun
中科院分区：
文献类型：
--
作者：
Zhang Wuchao;Gao Peng;Gui Xixi;Zhou Lei;Ge Xinna;Guo Xin;Wills John W.;Han Jun;Yang Hanchun
HSV-1 gI 是病毒在宿主体内进行细胞间传播所必需的，但人们对 gI 究竟如何发挥作用的分子机制仍知之甚少。在这里，我们报告了该分子的一个新特性，即诱导杆状结构，它似乎代表了 gI 的高阶形式。我们进一步绘制了关键残基图谱，并表明 gI 诱导杆状结构的能力与 HSV-1 在 UL24syn 背景下诱导细胞融合的能力密切相关，表明这两个事件可能具有内在联系。我们的结果揭示了 HSV-1 gI 的生物学特性，可能对理解病毒发病机制具有重要意义。摘要 单纯疱疹病毒 1 (HSV-1) 的包膜糖蛋白 I (gI) 是病毒诱导的细胞间传播和细胞间融合的关键介质。在这里，我们报告了该分子以前未被识别的特性。在转染的细胞中，HSV-1 gI被发现诱导出宽度均匀但长度可变的杆状结构。此外，这些结构中的gI在构象上与gI的典型形式不同，因为先前使用的单克隆抗体mAb3104和新制备的针对gI胞外结构域（ECD）（氨基酸[aa] 110至202）的肽抗体均未能对长杆状结构进行染色，表明形成了更高级的形式。与这一观察结果一致，我们发现 gI 可以自我相互作用，并且杆状结构无法识别糖蛋白 E（gI 众所周知的结合伴侣）。通过缺失诱变和构建 gI 和 gD 嵌合突变体的进一步分析表明，gI ECD 是关键的决定因素，而跨膜结构域仅充当锚点。随后将关键氨基酸定位到保守 PXXP 基序内的脯氨酸残基 184 和 188。反向遗传学分析表明，诱导杆状结构的能力并不是病毒在细胞培养物中复制和传播所必需的，而是与病毒在 UL24syn 背景下诱导细胞融合的能力呈正相关。总之，这项工作发现了 HSV-1 gI 的一个新特征，可能对理解 gI 在病毒传播和发病机制中的功能具有重要意义。重要性 HSV-1 gI 是病毒在宿主体内进行细胞间传播所必需的，但人们对 gI 究竟如何发挥作用的分子机制仍知之甚少。在这里，我们报告了该分子的一个新特性，即诱导杆状结构，它似乎代表了 gI 的高阶形式。我们进一步绘制了关键残基图谱，并表明 gI 诱导杆状结构的能力与 HSV-1 在 UL24syn 背景下诱导细胞融合的能力密切相关，表明这两个事件可能具有内在联系。我们的结果揭示了 HSV-1 gI 的生物学特性，可能对理解病毒发病机制具有重要意义。
The HSV-1 gI is required for viral cell-to-cell spread within the host, but the molecular mechanisms of how gI exactly works have remained poorly understood. Here, we report a novel property of this molecule, namely, induction of rod-shaped structures, which appeared to represent a higher-order form of gI. We further mapped the critical residues and showed that the ability of gI to induce rod-shaped structures correlated well with the capability of HSV-1 to induce cell fusion in the UL24syn background, suggesting that the two events may have an intrinsic link. Our results shed light on the biological properties of HSV-1 gI and may have important implications in understanding viral pathogenesis. ABSTRACT The envelope glycoprotein I (gI) of herpes simplex virus 1 (HSV-1) is a critical mediator of virus-induced cell-to-cell spread and cell-cell fusion. Here, we report a previously unrecognized property of this molecule. In transfected cells, the HSV-1 gI was discovered to induce rod-shaped structures that were uniform in width but variable in length. Moreover, the gI within these structures was conformationally different from the typical form of gI, as a previously used monoclonal antibody mAb3104 and a newly made peptide antibody to the gI extracellular domain (ECD) (amino acids [aa] 110 to 202) both failed to stain the long rod-shaped structures, suggesting the formation of a higher-order form. Consistent with this observation, we found that gI could self-interact and that the rod-shaped structures failed to recognize glycoprotein E, the well-known binding partner of gI. Further analyses by deletion mutagenesis and construction of chimeric mutants between gI and gD revealed that the gI ECD is the critical determinant, whereas the transmembrane domain served merely as an anchor. The critical amino acids were subsequently mapped to proline residues 184 and 188 within a conserved PXXXP motif. Reverse genetics analyses showed that the ability to induce a rod-shaped structure was not required for viral replication and spread in cell culture but rather correlated positively with the capability of the virus to induce cell fusion in the UL24syn background. Together, this work discovered a novel feature of HSV-1 gI that may have important implications in understanding gI function in viral spread and pathogenesis. IMPORTANCE The HSV-1 gI is required for viral cell-to-cell spread within the host, but the molecular mechanisms of how gI exactly works have remained poorly understood. Here, we report a novel property of this molecule, namely, induction of rod-shaped structures, which appeared to represent a higher-order form of gI. We further mapped the critical residues and showed that the ability of gI to induce rod-shaped structures correlated well with the capability of HSV-1 to induce cell fusion in the UL24syn background, suggesting that the two events may have an intrinsic link. Our results shed light on the biological properties of HSV-1 gI and may have important implications in understanding viral pathogenesis.
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4.4
作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
5.4
作者：
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通讯作者：
Charles E. Saldanha;J. Lubinski;Claudia Martin;T. Nagashunmugam;Liyang Wang;H. van der Keyl;R. Tal-Singer;Harvey M Friedman
影响因子：
5.4
作者：
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通讯作者：
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