Interplay between rabies virus and the mammalian immune system  

作　　者：Nicholas Johnson Adam F Cunningham 

机构地区：[1]Animal and Plant Health Agency [2]Institute of Microbiology and Infection, School of Immunity and Infection, University of Birmingham

出　　处：《World Journal of Clinical Infectious Diseases》2015年第4期67-76,共10页世界临床传染病学杂志

基　　金：Supported by The European Union Seventh Framework Programme through project ANTIGONE:Anticipating the global onset of novel epidemics,No.278976

摘　　要：Rabies is a disease caused following infection of the brainby the rabies virus(RABV). The principle mechanism of transmission is through a bite wound. The virus infects peripheral nerves and moves to the central nervous system(CNS). There appears to be little involvement of other organ systems and little detectable immune stimulation prior to infection of the CNS. This failure of the mammalian immune system to respond to rabies virus infection leads, in the overwhelming majority of cases, to death of the host. To some extent, this failure is likely due to the exclusive replication of RABV in neurons and the limited ability to generate, sufficiently rapidly, an anti-viral antibody response in situ. This is reflected in the ability of post-exposure vaccination, when given early after infection, to prevent disease. The lack of immune stimulation during RABV infection preceding neural invasion is the Achilles heel of the immune response. Whilst many viruses infect the brain, causing encephalitis and neuronal deficit, none are as consistently fatal to the host as RABV. This is in part due to prior replication of many viruses in peripheral, non-neural tissue by other viruses that allows timely activation of the immune response before the host is overwhelmed. Our current understanding of the correlates of protection for rabies suggests that it is the action of neutralising antibodies that prevent infection and control spread of RABV. Furthermore, it tells us that the induction of immunity can protect and understanding how and why this happens is critical to controlling infection. However, the paradigm of antibody development suggests that antigen presentation overwhelmingly occurs in lymphoid tissue(germinal and non-germinal centres) and these are external to the CNS. In addition, the blood-brain-barrier may provide a block to the delivery of immune effectors(antibodies/plasma B-cells) entering where they are needed. Alternatively, there may be insufficient antigen exposure after natural infection to mount an effective Rabies is a disease caused following infection of the brainby the rabies virus(RABV). The principle mechanism of transmission is through a bite wound. The virus infects peripheral nerves and moves to the central nervous system(CNS). There appears to be little involvement of other organ systems and little detectable immune stimulation prior to infection of the CNS. This failure of the mammalian immune system to respond to rabies virus infection leads, in the overwhelming majority of cases, to death of the host. To some extent, this failure is likely due to the exclusive replication of RABV in neurons and the limited ability to generate, sufficiently rapidly, an anti-viral antibody response in situ. This is reflected in the ability of post-exposure vaccination, when given early after infection, to prevent disease. The lack of immune stimulation during RABV infection preceding neural invasion is the Achilles heel of the immune response. Whilst many viruses infect the brain, causing encephalitis and neuronal deficit, none are as consistently fatal to the host as RABV. This is in part due to prior replication of many viruses in peripheral, non-neural tissue by other viruses that allows timely activation of the immune response before the host is overwhelmed. Our current understanding of the correlates of protection for rabies suggests that it is the action of neutralising antibodies that prevent infection and control spread of RABV. Furthermore, it tells us that the induction of immunity can protect and understanding how and why this happens is critical to controlling infection. However, the paradigm of antibody development suggests that antigen presentation overwhelmingly occurs in lymphoid tissue(germinal and non-germinal centres) and these are external to the CNS. In addition, the blood-brain-barrier may provide a block to the delivery of immune effectors(antibodies/plasma B-cells) entering where they are needed. Alternatively, there may be insufficient antigen exposure after natural infection to mount an effective

关 键 词：RABIES virus Immune STIMULATION Central nervous system VACCINATION BLOOD-BRAIN-BARRIER 

分 类 号：R[医药卫生]