Collins N D, Newbound G C, Albrecht B, Beard J L, Ratner L, Lairmore M D
Center for Retrovirus Research and the Department of Veterinary Biosciences, The Ohio State University, Columbus, OH 43210-1093, USA.
Blood. 1998 Jun 15;91(12):4701-7.
Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia and HTLV-1-associated myelopathy. Novel, yet conserved RNA transcripts encoded from open reading frames (ORFs) I and II of the viral pX region are expressed both in vitro and in infected individuals. The ORF I mRNA encodes the protein p12(I), which has been shown to localize to cellular endomembranes, cooperate with bovine papillomavirus E5 in transformation, as well as bind to the IL-2 receptor beta and gamma chains and the H+ vacuolar ATPase. It is unknown what role p12(I) plays in the viral life cycle. Using an infectious molecular clone of HTLV-1 (ACH) and a derivative clone, ACH.p12(I), which fails to produce the p12(I) message, we investigated the importance of p12(I) in infected primary cells and in a rabbit model of the infection. ACH.p12(I) was infectious in vitro as shown by viral passage in culture and no qualitative or quantitative differences were noted between ACH and ACH.p12(I) in posttransfection viral antigen production. However, in contrast to ACH, ACH.p12(I) failed to establish persistent infection in vivo as indicated by reduced anti-HTLV-1 antibody responses, failure to demonstrate viral p19 antigen production in peripheral blood mononuclear cell (PBMC) cultures, and only transient detection of provirus by polymerase chain reaction in PBMC from ACH.p12(I)-inoculated rabbits. These results are the first to show the essential role of HTLV-1 p12(I) in the establishment of persistent viral infection in vivo and suggest potential new targets in antiviral strategies to prevent HTLV-1 infection.
人类嗜T淋巴细胞病毒1型（HTLV-1）是成人T细胞白血病和HTLV-1相关脊髓病的病原体。病毒pX区域开放阅读框（ORF）I和II编码的新型且保守的RNA转录本在体外和受感染个体中均有表达。ORF I mRNA编码蛋白p12（I），该蛋白已被证明定位于细胞内膜，在转化过程中与牛乳头瘤病毒E5协同作用，还能与白细胞介素-2受体β链和γ链以及H⁺空泡型ATP酶结合。目前尚不清楚p12（I）在病毒生命周期中发挥何种作用。我们使用HTLV-1的感染性分子克隆（ACH）和一个不能产生p12（I）信使RNA的衍生克隆ACH.p12（I），研究了p12（I）在受感染原代细胞和兔感染模型中的重要性。ACH.p12（I）在体外具有感染性，如在培养物中的病毒传代所示，并且在转染后病毒抗原产生方面，ACH和ACH.p12（I）之间未观察到定性或定量差异。然而，与ACH不同，ACH.p12（I）在体内未能建立持续感染，这表现为抗HTLV-1抗体反应降低、在外周血单核细胞（PBMC）培养物中未能检测到病毒p19抗原产生，以及在接种ACH.p12（I）的兔的PBMC中通过聚合酶链反应仅短暂检测到前病毒。这些结果首次表明HTLV-1 p12（I）在体内建立持续病毒感染中的重要作用，并提示了预防HTLV-1感染的抗病毒策略中的潜在新靶点。
