Titti Fausto, Zamarchi Rita, Maggiorella Maria Teresa, Sernicola Leonardo, Geraci Andrea, Negri Donatella Rita Maria, Borsetti Alessandra, Menin Chiara, D'Andrea Emma, Modesti Andrea, Masuelli Laura, Verani Paola, Chieco-Bianchi Luigi, Amadori Alberto
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
J Med Virol. 2002 Sep;68(1):129-40. doi: 10.1002/jmv.10179.
Simian immunodeficiency virus (SIV) as well as human immunodeficiency virus (HIV) induce polyclonal B-cell activation and are associated with the appearance of lymphomas in their respective hosts in either the presence or the absence of other co-infecting viruses such as Epstein-Barr virus (EBV). However, the pathogenic role of these retroviruses in the development of lymphoproliferative disorders remains poorly understood. To explore the virus-B-cell interactions, two immortalized lymphoblastoid B-cell lines (SL-P1 and SL-691) were established from cynomolgus monkeys that were naturally co-infected with a simian type D retrovirus-2 (SRV-2) and with the herpes virus Macaca fascicularis (HVMF-1). We addressed their susceptibility to SIV infection and the phenotypic modifications associated with SIV infection. In response, both cell lines (1) were co-infected with HVMF-1 (latent infection) and with SRV-2 (productive infection), (2) had a transformed phenotype because they did not require exogenous growth factors, and (3) when injected into mice with severe combined immunodeficiency (SCID), generated serially transplantable tumors. The B-cell origin of SL cells was demonstrated by the presence of rearrangements of the IgH gene and by the expression of typical B-cell lineage markers, such as CD20. SL-P1 and SL-691 could be discriminated on the basis of different expressions of CD23 and CD40 and of kappa- and lambda-chains. Most importantly, SL-691 cells, but not SL-P1 cells, were susceptible to chronic noncytolytic SIV infection. This infection occurred in a CD4/CCR5/CXCR4-independent manner and was associated with the upregulated expression of CD23 and CD40 cell surface markers. In addition, CD20 expression, which progressively disappeared in SL-691 noninfected cells, was maintained in the SIV-infected counterpart. These findings support the hypothesis that SIV induce phenotypic perturbations in B cells that might eventually contribute to the development of lymphoproliferative disease.
猿猴免疫缺陷病毒（SIV）以及人类免疫缺陷病毒（HIV）均可诱导多克隆B细胞活化，并且无论是否存在其他共感染病毒，如爱泼斯坦-巴尔病毒（EBV），它们都与各自宿主中淋巴瘤的出现有关。然而，这些逆转录病毒在淋巴增生性疾病发展中的致病作用仍知之甚少。为了探究病毒与B细胞的相互作用，我们从自然感染了猿猴D型逆转录病毒2型（SRV-2）和猕猴疱疹病毒（HVMF-1）的食蟹猴中建立了两种永生化淋巴母细胞系（SL-P1和SL-691）。我们研究了它们对SIV感染的易感性以及与SIV感染相关的表型改变。结果发现，这两种细胞系：（1）同时感染了HVMF-1（潜伏感染）和SRV-2（增殖性感染）；（2）具有转化表型，因为它们不需要外源性生长因子；（3）当注射到严重联合免疫缺陷（SCID）小鼠体内时，可产生可连续移植的肿瘤。通过免疫球蛋白重链（IgH）基因重排的存在以及典型B细胞谱系标志物如CD20的表达，证实了SL细胞的B细胞起源。SL-P1和SL-691可以根据CD23和CD40以及κ链和λ链的不同表达进行区分。最重要的是，SL-691细胞而非SL-P1细胞易受慢性非细胞溶解性SIV感染。这种感染以不依赖CD4/CCR5/CXCR4的方式发生，并与CD23和CD40细胞表面标志物的表达上调有关。此外，在未感染的SL-691细胞中逐渐消失的CD20表达，在感染SIV的对应细胞中得以维持。这些发现支持了以下假设：SIV可诱导B细胞发生表型扰动，最终可能导致淋巴增生性疾病的发展。
