Organ-specific selection of viral variants during chronic infection.

Organ-specific selection of viral variants during chronic infection.
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DOI:
10.1084/jem.167.5.1719
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发表时间:
1988-05-01
影响因子:
15.3
通讯作者:
OLDSTONE, MBA
OLDSTONE, MBA
中科院分区:
医学1区
文献类型:
--
作者:
AHMED, R;OLDSTONE, MBA

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这项研究证明了慢性淋巴细胞脉络膜脑膜炎病毒(LCMV)在其自然宿主感染过程中病毒变体的器官特异性选择。出生时感染 LCMV 野生型阿姆斯特朗株的携带者小鼠的中枢神经系统 (CNS) 和淋巴组织中存在具有不同生物学特性的分离株。从中枢神经系统分离出的病毒与野生型阿姆斯特朗毒株相似,在成年小鼠中诱导了强效的病毒特异性细胞毒性 T 淋巴细胞 (CTL) 反应,并且感染在 2 周内被清除。相比之下,来自淋巴组织的 LCMV 分离株在成年小鼠中引起慢性感染,并与抑制 CTL 反应相关。具有野生型阿姆斯特朗表型的回复体存在于感染脾分离株的小鼠的中枢神经系统中,这明确地表明宿主组织在病毒变体选择中的重要性。这些结果提供了病毒变体在自然界中出现的可能机制,并表明组织和细胞特异性选择是病毒进化的一个重要方面。
This study demonstrates organ specific selection of viral variants during chronic lymphocytic choriomeningitis virus (LCMV) infection in its natural host. Isolates with different biological properties were present in the central nervous system (CNS) and lymphoid tissues of carrier mice infected at birth with the wt Armstrong strain of LCMV. Viral isolates from the CNS were similar to the wt Armstrong strain and induced potent virus-specific cytotoxic T lymphocyte (CTL) responses in adult mice and the infection was cleared within 2 wk. In contrast, LCMV isolates derived from the lymphoid tissues caused a chronic infection in adult mice associated with suppressed CTL responses. Revertants with wt Armstrong phenotype were present in the CNS of mice infected with a spleen isolate showing unequivocally the importance of host tissues in the selection of viral variants. These results provide a possible mechanism by which viral variants emerge in nature and suggest that tissue- and cell-specific selection is an important aspect of virus evolution.
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