Fassone Lucia, Cingolani Antonella, Martini Maurizio, Migliaretti Giuseppe, Oreste Pier Luigi, Capello Daniela, Gloghini Annunziata, Vivenza Daniela, Dolcetti Riccardo, Carbone Antonino, Antinori Andrea, Gaidano Gianluca, Larocca Luigi Maria
Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
AIDS Res Hum Retroviruses. 2002 Jan 1;18(1):19-26. doi: 10.1089/088922202753394682.
In the present study sequence variations at the C terminus of the Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1), EBV-encoded latent membrane protein 1 (LMP-1), and EBNA-2 and EBNA-3C genes were investigated in 64 cases of EBV-positive AIDS-related diffuse large cell lymphoma (AIDS-DLCL), both systemic (12) and localized primarily to the central nervous system (52), and in 12 cases of EBV-positive AIDS-related Burkitt's lymphoma (AIDS-BL). Sequence analysis of the EBNA-1 C-terminal region led to the distinction of two major unrelated EBV strains, termed strain P (prototype) and strain V (variant), and their related subtypes, namely P-ala, P-thr, V-leu, V-val, and V-pro. Analysis of the LMP-1 gene was performed to assess the frequency of the C-terminus deletion variant, whereas analysis of EBNA-2 and EBNA-3C genes led to the identification of the distribution of the EBV type 1 and type 2 strains. The frequency of EBNA-1 subtypes was assessed in 49 cases of AIDS-NHL, including 37 cases of AIDS-DLCL and 12 cases of AIDS-BL. The P strain was detected in 45 of 49 cases (91.8%) whereas the V strain was found in 4 of 49 samples (8.1%). A significant difference in the distribution of the P and V strains was found between AIDS-DLCL and AIDS-BL (p < 0.01), because of the exclusive infection by the P strain of the AIDS-DLCL samples analyzed. The frequency of LMP-1 deletion variants and of EBV type 1 and type 2 strains in AIDS-DLCL overlapped with that of the general population, and no correlation was found with the evaluated clinicoepidemiological data of patients, that is, disease site, tumor histology, CD4(+) cell counts, and HIV transmission route. In conclusion, we found that the distribution of the EBV genotype in all of the AIDS-NHL samples analyzed is similar to the viral representation found in control individuals of both immunocompetent and immunocompromised populations.
在本研究中，我们调查了64例EB病毒（EBV）阳性的艾滋病相关弥漫性大细胞淋巴瘤（AIDS-DLCL）患者（包括12例全身性和52例主要局限于中枢神经系统的病例）以及12例EBV阳性的艾滋病相关伯基特淋巴瘤（AIDS-BL）患者中EBV核抗原1（EBNA-1）、EBV编码的潜伏膜蛋白1（LMP-1）、EBNA-2和EBNA-3C基因C末端的序列变异情况。对EBNA-1 C末端区域的序列分析区分出了两种主要的不相关EBV毒株，分别称为P毒株（原型）和V毒株（变异型）及其相关亚型，即P-ala、P-thr、V-leu、V-val和V-pro。对LMP-1基因进行分析以评估C末端缺失变异体的频率，而对EBNA-2和EBNA-3C基因的分析则确定了EBV 1型和2型毒株的分布情况。在49例艾滋病相关非霍奇金淋巴瘤（AIDS-NHL）患者中评估了EBNA-1亚型的频率，其中包括37例AIDS-DLCL和12例AIDS-BL。在49例病例中的45例（91.8%）检测到P毒株，而在49个样本中的4个（8.1%）发现了V毒株。在AIDS-DLCL和AIDS-BL之间，P毒株和V毒株的分布存在显著差异（p<0.01），这是因为所分析的AIDS-DLCL样本仅感染了P毒株。AIDS-DLCL中LMP-1缺失变异体以及EBV 1型和2型毒株的频率与普通人群重叠，并且与所评估的患者临床流行病学数据（即疾病部位、肿瘤组织学、CD4(+)细胞计数和HIV传播途径）没有相关性。总之，我们发现所有分析的AIDS-NHL样本中EBV基因型的分布与免疫功能正常和免疫功能低下人群的对照个体中发现的病毒表现相似。
