Hochberg Donna, Middeldorp Jaap M, Catalina Michelle, Sullivan John L, Luzuriaga Katherine, Thorley-Lawson David A
Department of Pathology, Tufts University School of Medicine, Jaharis Building, 150 Harrison Avenue, Boston, MA 02111, USA.
Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):239-44. doi: 10.1073/pnas.2237267100. Epub 2003 Dec 19.
Epstein-Barr virus (EBV) is a herpesvirus that establishes a lifelong, persistent infection. It was first discovered in the tumor Burkitt's lymphoma (BL). Despite intensive study, the role of EBV in BL remains enigmatic. One striking feature of the tumor is the unique pattern of viral latent protein expression, which is restricted to EBV-encoded nuclear antigen (EBNA) 1. EBNA1 is required to maintain the viral genome but is not recognized by cytotoxic T cells. Consequently, it was proposed that this expression pattern was used by latently infected B cells in vivo. This would be the site of long-term, persistent infection by the virus and, by implication, the progenitor of BL. We now know that EBV persists in memory B cells in the peripheral blood and that BL is a tumor of memory cells. However, a normal B cell expressing EBNA1 alone has been elusive. Here we show that most infected cells in the blood express no detectable latent mRNA or proteins. The exception is that when infected cells divide they express EBNA1 only. This is the first detection of the BL viral phenotype in a normal, infected B cell in vivo. It suggests that BL may be a tumor of a latently infected memory B cell that is stuck proliferating because it is a tumor and, therefore, constitutively expressing only EBNA1.
爱泼斯坦-巴尔病毒（EBV）是一种能建立终身持续性感染的疱疹病毒。它最初是在伯基特淋巴瘤（BL）肿瘤中被发现的。尽管进行了深入研究，但EBV在BL中的作用仍然成谜。该肿瘤的一个显著特征是病毒潜伏蛋白表达的独特模式，这种模式仅限于爱泼斯坦-巴尔病毒编码的核抗原（EBNA）1。EBNA1是维持病毒基因组所必需的，但不被细胞毒性T细胞识别。因此，有人提出这种表达模式在体内被潜伏感染的B细胞所采用。这将是病毒长期持续性感染的部位，并且暗示着它是BL的祖细胞。我们现在知道EBV在外周血的记忆B细胞中持续存在，并且BL是一种记忆细胞肿瘤。然而，仅表达EBNA1的正常B细胞一直难以找到。在这里我们表明，血液中大多数受感染的细胞没有可检测到的潜伏mRNA或蛋白。例外情况是，当受感染细胞分裂时，它们仅表达EBNA1。这是首次在体内正常受感染的B细胞中检测到BL病毒表型。这表明BL可能是一种潜伏感染的记忆B细胞肿瘤，由于它是肿瘤，所以一直处于增殖状态，因此仅组成性表达EBNA1。
