Ota A, Ueda S
Department of Neurovirology, Research Institute for Microbial Diseases, Osaka University, Japan.
Hybridoma. 1999 Jun;18(3):235-41. doi: 10.1089/027245799315880.
We have studied the immunological role of human immunodeficiency virus type 1 (HIV-1) p17 because the p17 antibody titer is high in asymptomatic patients and decreases with disease progression. Previously we found that monoclonal antibody (MAb) reactive to the p17-derived peptide 30 to 52 amino acids in length, namely P30-52 MAb, had cross-reactivity to the third variable region of the envelope glycoprotein of HIV-1 (Env V3) and also inhibited the viral multiplication of the supernatant of HIV-1-infected MT-4 cells co-cultured with the MAb. The relation between the cross-reactivity of the P30-52 MAb and the inhibitory mechanism is not clear; however, P30-52 might be useful for the development of therapeutic and vaccination strategies. In the present study, we examined the suppressive mechanism of the P30-52 MAbs, and found that the copy number of HIV-1 RNA in HIV-1-infected MT-4 cells was not reduced by the addition of the P30-52 MAbs, and the expression of RNAs of p17 was slightly enhanced 3 hr after the infection, although that of Env V3 was the same as the control level. In contrast, the expression of cellular p17 DNA and p17 protein was reduced by the addition of the P30-52 MAbs. In conclusion, the P30-52 MAbs did not suppress the HIV-1 mRNA level in the infected cells, but might inhibit DNA synthesis, and consequently bring about a reduction of p17 protein synthesis and a decrease of infectivity of the supernatant. The results demonstrated that the P30-52 MAb could be used as immunotherapeutic substance for HIV-1.
我们研究了人类免疫缺陷病毒1型（HIV-1）p17的免疫作用，因为在无症状患者中p17抗体滴度较高，且会随着疾病进展而降低。此前我们发现，与长度为30至52个氨基酸的p17衍生肽反应的单克隆抗体（MAb），即P30-52 MAb，与HIV-1包膜糖蛋白的第三个可变区（Env V3）有交叉反应，并且还抑制了与该MAb共培养的HIV-1感染的MT-4细胞上清液的病毒增殖。P30-52 MAb的交叉反应性与抑制机制之间的关系尚不清楚；然而，P30-52可能对治疗和疫苗策略的开发有用。在本研究中，我们研究了P30-52 MAb的抑制机制，发现添加P30-52 MAb并不会降低HIV-1感染的MT-4细胞中HIV-1 RNA的拷贝数，并且在感染后3小时，p17的RNA表达略有增强，尽管Env V3的RNA表达与对照水平相同。相反，添加P30-52 MAb会降低细胞p17 DNA和p17蛋白 的表达。总之，P30-52 MAb不会抑制感染细胞中HIV-1 mRNA的水平，但可能会抑制DNA合成，从而导致p17蛋白合成减少以及上清液感染性降低。结果表明，P30-52 MAb可作为HIV-1的免疫治疗物质。
