Laskus T, Radkowski M, Wang L F, Jang S J, Vargas H, Rakela J
Thomas E. Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, Pennsylvania, 15213, USA.
Virology. 1998 Aug 15;248(1):164-71. doi: 10.1006/viro.1998.9269.
Hepatitis C virus (HCV) sequences recovered from serum, peripheral blood mononuclear cells (PBMCs), and various tissues from human immunodeficiency virus type 1 (HIV-1) positive patients were compared by single strand conformational polymorphism (SSCP) and sequencing. In five patients, paired serum and PBMCs samples were analyzed while in two other patients multiple autopsy tissues were studied. Sequences amplified from the NS5 and E2 regions were consistently identical in the same patient; however, three PBMCs samples and three different tissue samples (pancreas and adrenal gland in one patient and lymph node in the other patient) contained 5' untranslated region (5'UTR) sequences that were different from circulating sequences. The presence of 5' UTR sequences differing from circulating sequences correlated with the presence of HCV RNA negative strand, as the latter was detected by a Tth-based strand-specific assay in all but one of these samples. These two independent lines of evidence: viral sequence differences and the presence of RNA negative strand in the same tissues strongly argue for the genuine presence of extrahepatic HCV replication, at least in the setting of HIV-1 infection.
通过单链构象多态性（SSCP）和测序，对从人类免疫缺陷病毒1型（HIV-1）阳性患者的血清、外周血单核细胞（PBMC）及各种组织中获得的丙型肝炎病毒（HCV）序列进行了比较。在5名患者中分析了配对的血清和PBMC样本，同时在另外2名患者中研究了多个尸检组织。从NS5和E2区域扩增的序列在同一患者中始终相同；然而，3份PBMC样本和3份不同的组织样本（1名患者的胰腺和肾上腺以及另1名患者的淋巴结）含有与循环序列不同的5'非翻译区（5'UTR）序列。与循环序列不同的5'UTR序列的存在与HCV RNA负链的存在相关，因为在除1份样本外的所有这些样本中，通过基于Tth的链特异性检测法检测到了后者。这两条独立的证据线：病毒序列差异以及同一组织中RNA负链的存在，有力地证明了肝外HCV复制的真实存在，至少在HIV-1感染的情况下是如此。
