Department of Internal Medicine, Division of Infectious Diseases, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
Interdisciplinary Program on Molecular and Cellular Biology, Iowa City Veterans Affairs Medical Center and the University of Iowa, Iowa City, IA 52242, USA.
J Gen Virol. 2013 Apr;94(Pt 4):774-782. doi: 10.1099/vir.0.047126-0. Epub 2013 Jan 3.
GB virus type C (GBV-C) is a lymphotropic virus that can cause persistent infection in humans. GBV-C is not associated with any disease, but is associated with reduced mortality in human immunodeficiency virus type 1 (HIV-1)-infected individuals. Related viruses have been isolated from chimpanzees (GBV-Ccpz) and from New World primates (GB virus type A, GBV-A). These viruses are also capable of establishing persistent infection. We determined the nucleotide sequence encoding the envelope glycoprotein (E2) of two GBV-Ccpz isolates obtained from the sera of captive chimpanzees. The deduced GBV-Ccpz E2 protein differed from human GBV-C by 31 % at the amino acid level. Similar to human GBV-C E2, expression of GBV-Ccpz E2 in a tet-off human CD4(+) Jurkat T-cell line significantly inhibited the replication of diverse HIV-1 isolates. This anti-HIV-replication effect of GBV-Ccpz E2 protein was reversed by maintaining cells in doxycycline to reduce E2 expression. Previously, we found a 17 aa region within human GBV-C E2 that was sufficient to inhibit HIV-1. Although GBV-Ccpz E2 differed by 3 aa differences in this region, the chimpanzee GBV-C 17mer E2 peptide inhibited HIV-1 replication. Similarly, the GBV-A peptide that aligns with this GBV-C E2 region inhibited HIV-1 replication despite sharing only 5 aa with the human GBV-C E2 sequence. Thus, despite amino acid differences, the peptide region on both the GBV-Ccpz and the GBV-A E2 protein inhibit HIV-1 replication similar to human GBV-C. Consequently, GBV-Ccpz or GBV-A infection of non-human primates may provide an animal model to study GB virus-HIV interactions.
GB 病毒 C（GBV-C）是一种嗜淋巴细胞病毒，可在人类中引起持续性感染。GBV-C 与任何疾病均无关，但与人类免疫缺陷病毒 1（HIV-1）感染个体的死亡率降低相关。已从黑猩猩（GBV-Ccpz）和新世界灵长类动物（GB 病毒 A，GBV-A）中分离出相关病毒，这些病毒也能够建立持续性感染。我们测定了从圈养黑猩猩血清中获得的两个 GBV-Ccpz 分离株编码包膜糖蛋白（E2）的核苷酸序列。推导的 GBV-Ccpz E2 蛋白在氨基酸水平上与人 GBV-C 相差 31%。与人类 GBV-C E2 相似，在 tet-off 人 CD4+ Jurkat T 细胞系中表达的 GBV-Ccpz E2 显著抑制了多种 HIV-1 分离株的复制。用多西环素维持细胞以减少 E2 表达，可逆转 GBV-Ccpz E2 蛋白的抗 HIV 复制作用。此前，我们发现人类 GBV-C E2 中的 17 个氨基酸区域足以抑制 HIV-1。尽管 GBV-Ccpz E2 在该区域有 3 个氨基酸差异，但黑猩猩 GBV-C 17mer E2 肽抑制了 HIV-1 的复制。同样，与该 GBV-C E2 区域对齐的 GBV-A 肽尽管与人类 GBV-C E2 序列仅共享 5 个氨基酸，但也抑制了 HIV-1 的复制。因此，尽管存在氨基酸差异，但 GBV-Ccpz 和 GBV-A E2 蛋白上的肽区域抑制 HIV-1 复制的方式与人类 GBV-C 相似。因此，GBV-Ccpz 或 GBV-A 感染非人类灵长类动物可能为研究 GB 病毒-HIV 相互作用提供动物模型。
