Viral pathogenesis and resistance to defective interfering particles
Viral pathogenesis and resistance to defective interfering particles
复制标题
病毒发病机制和对缺陷干扰颗粒的抵抗力
作者：
S. Jacobson;C. Pfau
最近提出的证据表明，淋巴细胞脉络膜脑膜炎(LCM)病毒感染培养细胞后，缺陷干扰(DI)颗粒的合成可能导致自愈。DI颗粒的产生可以发生在感染了几乎任何动物病毒的细胞中2，而且似乎是宿主控制的功能3。因此，这些颗粒可能是抵抗病毒入侵的第三道防线--免疫反应和干扰素3，4。LCM病毒感染导致组织培养细胞中DI颗粒迅速出现5，6。然而，LCM和其他病毒可以很容易地建立持续性感染7-9。在这些培养物中，LCM持续感染显然是通过耐DI病毒的发生而维持的。后一项发现促使我们确定这种耐DI病毒是否在自然界中存在。LCM病毒在家鼠或实验室小鼠新生感染中的垂直传播采取终生亲本感染的形式。这些小鼠缺乏功能性的病毒特异性T淋巴细胞，但可能会对入侵做出抗体反应。众所周知，注射到新生小鼠体内的LCM病毒可以在感染过程中发生变化，因此至少两种不同的病毒种群在同一只小鼠中共存10。在新生儿感染后不久就会产生大量的DI颗粒，这是出现病毒群体的先兆，从斑块形态来看，该病毒群体与最初接种的病毒不同11。我们在这里报告从持续感染的小鼠中分离出一种LCM病毒，该病毒不仅对新生儿感染异型病毒后不久产生的DI颗粒具有抵抗力，而且对该病毒本身在新生儿中诱导的DI颗粒具有抵抗力。据我们所知，没有其他关于病毒在它们诱导的DI颗粒存在的情况下可以正常复制的报告。
Recently presented evidence indicates that synthesis of defective interfering (DI) particles following infection of cultured cells with lymphocytic choriomeningitis (LCM) virus may result in self-curing1. The genesis of DI particles can occur in cells infected with virtually any animal virus2, and seems to be a host-controlled function3. Thus, these particles may represent a third line of defence—with the immune response and interferon—against virus invasion3,4. LCM virus infection causes the rapid appearance of DI particles in tissue culture cells5,6. Nevertheless, persistent infections can be easily established with LCM and other arenaviruses7–9. The LCM-persistent infections are apparently maintained in these cultures by the genesis of DI-resistant viruses1. This latter finding prompted us to determine whether such DI-resistant viruses occur in nature. Vertical transmission of LCM virus in the house mouse or neonatal infection of laboratory mice takes the form of a life-long inap-parent infection. These mice lack functional virus-specific T lymphocytes, but may make an antibody response against the invasion. It is known that LCM virus injected into a neonatal mouse can change during the course of the infection so that at least two different viral populations coexist in the same mouse10. DI particles are produced in abundance shortly after neonatal infection and this precedes the appearance of a virus population that, by plaque morphology, differs from the one originally inoculated11. We report here the isolation of an LCM virus from persistently infected mice that is resistant not only to the DI particles which were produced shortly after neonatal infection with heterotypic virus but also to the DI particles that this virus itself induces in neonates. We know of no other report of viruses which can replicate normally in the presence of the DI particles they induce.