Genome-Wide Transcriptional Profiling Reveals Two Distinct Outcomes in Central Nervous System Infections of Rabies Virus

Rabies remains a major public health problem in many developing countries. The hypothesis is due to neuronal cell death or dysfunction, but the exact neuropathological outbreak of rabies is unknown. Intranasal vaccination with mouse attenuated rabies virus (RABV) strain HEP ​​- Flury showed subtle clinical symptoms and eventually recovered. This was caused by lethal encephalitis of virulent strain RABV CVS - 11. To understand the neuropathology and viral clearance mechanism of rabies, the inventors used RNA sequencing to compare normal mouse brain transcriptome with HEP-Flury or CVS-11 intranasally vaccinated mice RNA-Seq) was used. Our results show that both RABV strains significantly alter the expression levels of many host genes, including those related to congenital and adaptive immunity, inflammation and cell death. HEP - Flury infection can activate innate immunity early through RIG - I / MDA - 5 signaling and infection by HEP - Flury or Newcastle Disease Virus (NDV) is caused by central nervous system CVS innate immunity 11 (CNS) which can effectively prevent activation, but did not clear CVS-11 after entering CNS. In addition, genes involved in cell adhesion, angiogenesis and coagulation are predominantly upregulated following CVS - 11 infection, whereas genes involved in synaptic transmission and ion transport are significantly down - regulated. On the other hand, some genes involved in the MHC class II mediated antigen presentation pathway are activated to a greater extent after HEP - Flury infection and show CD4 + T cells and MHC class II compared to CVS - 11 infection . Collaboration mediated antigen presentation is important for the elimination of attenuated RABV from the CNS. Differentially regulated genes reported here may include potential therapeutic targets to expand the post-exposure treatment period for RABV infection.

From incoming wounds, rabies virus spreads rapidly along the nerve pathway of the peripheral nervous system. The retrograde axonal transport of rabies virus to the central nervous system (central nervous system) is an important step in the pathogenesis of natural infections. Binding of P protein from rabies virus to the dynein light chain protein DYNLL1 has been shown but the exact molecular mechanism of this transport is unknown. P also acts as an interferon antagonist, thereby lowering the immune response of the host

Rabies virus infects via the saliva of infected animals, but in most cases bite is caused. The virus enters the nerve with bite and enters the central nervous system (spinal cord and brain) where it grows. When it reaches the central nervous system, the virus is mostly deadly. Because of the widespread use of prophylactic vaccines in livestock, comprehensive animal care and public awareness, rabies deaths are rare in the United States. However, on a global scale, the disease is estimated to have 59,000 deaths annually, most of which are in Africa and Asia. Half of deaths occur in children under 15 years of age

Rabies is an infectious infection affecting the central nervous system, caused by a virus called rhabdovirus. The virus enters the body through the bite of an animal infected with rabies. Many mammals can carry this virus, but it is most common in dogs, skunks, foxes, bats, raccoons, and cats. Virus is usually present in neurons and glands of diseased hosts or carriers. Rabies can also be carried over the salivary glands for a long time. & Lt; Tab / & gt; There are two ways of rabies symptoms, fool and anger. Both can cause abnormal behavior. Prior to dying, animals suffering from rabies appear to be "crazy": their mouth is bubbling, biting something that hinders them. They show extreme excitement and may attack static things and animals. Onset of rabies rabies usually involves depression. In silly rabies, there is no "crazy" period