Cayabyab M, Hinuma S, Farzan M, Choe H, Fukusumi S, Kitada C, Nishizawa N, Hosoya M, Nishimura O, Messele T, Pollakis G, Goudsmit J, Fujino M, Sodroski J
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Virol. 2000 Dec;74(24):11972-6. doi: 10.1128/jvi.74.24.11972-11976.2000.
In addition to the CCR5 and CXCR4 chemokine receptors, a subset of primary human immunodeficiency virus type 1 (HIV-1) isolates can also use the seven-transmembrane-domain receptor APJ as a coreceptor. A previously identified ligand of APJ, apelin, specifically inhibited the entry of primary T-tropic and dualtropic HIV-1 isolates from different clades into cells expressing CD4 and APJ. Analysis of apelin analogues demonstrated that potent and specific antiviral activity was retained by a 13-residue, arginine-rich peptide. Antiviral potency was influenced by the integrity of methionine 75, which contributes to APJ-binding affinity, and by the retention of apelin residues 63 to 65. These studies demonstrate the ability of a small peptide ligand to block the function of APJ as an HIV-1 coreceptor, identify apelin sequences important for the inhibition, and provide new reagents for the investigation of the significance of APJ to HIV-1 infection and pathogenesis.
除CCR5和CXCR4趋化因子受体外，一部分原发性人类免疫缺陷病毒1型（HIV-1）分离株还可利用七跨膜结构域受体APJ作为共受体。先前鉴定出的APJ配体apelin可特异性抑制来自不同进化枝的原发性T嗜性和双嗜性HIV-1分离株进入表达CD4和APJ的细胞。对apelin类似物的分析表明，一种含13个残基、富含精氨酸的肽保留了高效且特异的抗病毒活性。抗病毒效力受有助于APJ结合亲和力的甲硫氨酸75的完整性以及apelin第63至65位残基保留情况的影响。这些研究证明了一种小肽配体阻断APJ作为HIV-1共受体功能的能力，确定了抑制作用中重要的apelin序列，并为研究APJ对HIV-1感染和发病机制的意义提供了新试剂。
