Peterhans E, Jungi T W, Schweizer M
Institut für Veterinar-Virologie, Universität Bern, Bern, Schweiz.
Dtsch Tierarztl Wochenschr. 2006 Apr;113(4):124-9.
The interaction of bovine viral diarrhea virus (BVD virus) with its host has several unique features, most notably the capacity to infect its host either transiently or persistently. The transient infection stimulates an antiviral immune reaction similar to that seen in other transient viral infections. In contrast, being associated with immunotolerance specific for the infecting BVD viral strain, the persistent infection differs fundamentally from other persistent infections like those caused by lentiviruses. Whereas the latter are characterized by complex viral evasion of the host's adaptive immune response by mechanisms such as antigenic drift and interference with presentation of T cell epitopes, BVD virus avoids the immune response altogether by inducing both humoral and cellular immune tolerance. This is made possible by invasion of the fetus at an early stage of development. In addition to adaptive immunity, BVD virus also manipulates key elements of the host's innate immune response. The non-cytopathic biotype of BVD virus, which is capable of persistently infecting its host, fails to induce type I interferon. In addition, persistently infected cells are resistant to the induction of apoptosis by double-stranded RNA and do not produce interferon when treated with this pathogen-associated molecular pattern (PAMP) that signals viral infection. Moreover, when treated with interferon, cells persistently infected with non-cytopathic BVD virus do not clear the virus. Surprisingly, however, despite this lack of effect on persistent infection, interferon readily induces an antiviral state in these cells, as shown by the protection against infection by unrelated viruses. Overall, BVD virus manipulates the host's interferon defense in a manner that optimises its chances of maintaining the persistent infection as well as decreasing the risks that heterologous viral infections may carry for the host. Thus, since not all potential host cells are infected in animals persistently infected with BVD virus, heterologous viruses replicating in cells uninfected with BVD virus will still trigger production of interferon. Interferon produced by such cells will curtail the replication of heterologous viruses only, be that in cells already infected with BVD virus, or in cells in which the heterologous virus may replicate alone. From an evolutionary viewpoint, this strategy clearly enhances the chances of transmission of BVD virus to new hosts, as it attenuates the negative effects that a global immunosuppression would have on the survival of persistently infected animals.
牛病毒性腹泻病毒（BVD病毒）与其宿主的相互作用具有几个独特的特征，最显著的是它能够短暂或持续地感染宿主。短暂感染会引发一种类似于其他短暂病毒感染中所见的抗病毒免疫反应。相比之下，持续感染与针对感染的BVD病毒株的免疫耐受相关，与其他持续性感染（如慢病毒引起的感染）有根本区别。后者的特征是通过抗原漂移和干扰T细胞表位呈递等机制，病毒对宿主的适应性免疫反应进行复杂的逃避，而BVD病毒通过诱导体液免疫和细胞免疫耐受完全避免免疫反应。这是通过在发育早期侵入胎儿来实现的。除了适应性免疫外，BVD病毒还操纵宿主固有免疫反应的关键要素。能够持续感染宿主的BVD病毒非致细胞病变生物型不会诱导I型干扰素。此外，持续感染的细胞对双链RNA诱导的凋亡具有抗性，并且在用这种指示病毒感染的病原体相关分子模式（PAMP）处理时不会产生干扰素。此外，在用干扰素处理时，被非致细胞病变BVD病毒持续感染的细胞不会清除病毒。然而，令人惊讶的是，尽管对持续感染没有这种作用，但干扰素很容易在这些细胞中诱导抗病毒状态，如对无关病毒感染的保护所示。总体而言，BVD病毒以一种优化其维持持续感染的机会并降低异源病毒感染可能给宿主带来的风险的方式操纵宿主的干扰素防御。因此，由于在持续感染BVD病毒的动物中并非所有潜在的宿主细胞都被感染，在未感染BVD病毒的细胞中复制的异源病毒仍会触发干扰素的产生。这种细胞产生的干扰素只会抑制异源病毒的复制，无论是在已经感染BVD病毒的细胞中，还是在异源病毒可能单独复制的细胞中。从进化的角度来看，这种策略显然增加了BVD病毒传播到新宿主的机会，因为它减轻了全球免疫抑制对持续感染动物生存的负面影响。
