Division of Infectious Diseases, Department of Internal Medicine, St. Louis University, St. Louis, Missouri, United States of America.
PLoS One. 2012;7(1):e30653. doi: 10.1371/journal.pone.0030653. Epub 2012 Jan 23.
Persistent infection with GBV-C (GB Virus C), a non-pathogenic virus related to hepatitis C virus (HCV), prolongs survival in HIV infection. Two GBV-C proteins, NS5A and E2, have been shown previously to inhibit HIV replication in vitro. We investigated whether the GBV-C NS3 serine protease affects HIV replication.
GBV-C NS3 protease expressed in a human CD4+ T lymphocyte cell line significantly inhibited HIV replication. Addition of NS4A or NS4A/4B coding sequence to GBV-C NS3 increased the effect on HIV replication. Inhibition of HIV replication was dose-dependent and was not mediated by increased cell toxicity. Mutation of the NS3 catalytic serine to alanine resulted in loss of both HIV inhibition and protease activity. GBV-C NS3 expression did not measurably decrease CD4 or CXCR4 expression.
GBV-C NS3 serine protease significantly inhibited HIV replication without decreasing HIV receptor expression. The requirement for an intact catalytic serine at the active site indicates that inhibition was mediated by proteolytic cleavage of an unidentified target(s).
GBV-C（GB 病毒 C）是一种与丙型肝炎病毒（HCV）相关的非致病性病毒，持续性感染可延长 HIV 感染患者的生存时间。先前已经证明，两种 GBV-C 蛋白 NS5A 和 E2 在体外抑制 HIV 复制。我们研究了 GBV-C NS3 丝氨酸蛋白酶是否影响 HIV 复制。
在人 CD4+T 淋巴细胞系中表达的 GBV-C NS3 蛋白酶显著抑制 HIV 复制。添加 NS4A 或 NS4A/4B 编码序列到 GBV-C NS3 增加了对 HIV 复制的影响。抑制 HIV 复制呈剂量依赖性，并且不是通过增加细胞毒性介导的。将 NS3 催化丝氨酸突变为丙氨酸导致 HIV 抑制和蛋白酶活性的丧失。GBV-C NS3 的表达不会明显降低 CD4 或 CXCR4 的表达。
GBV-C NS3 丝氨酸蛋白酶显著抑制 HIV 复制，而不降低 HIV 受体的表达。活性部位完整的催化丝氨酸的要求表明，抑制是通过对未鉴定的靶标（多个）的蛋白水解切割介导的。
