Neuroinvasion and Inflammation in Viral Central Nervous System Infections

Abstract

Neurotropic viruses can cause devastating central nervous system (CNS) infections, especially in young children and the elderly. The blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) have been described as relevant sites of entry for specific viruses as well as for leukocytes, which are recruited during the proinflammatory response in the course of CNS infection. In this review, we illustrate examples of established brain barrier models, in which the specific reaction patterns of different viral families can be analyzed. Furthermore, we highlight the pathogen specific array of cytokines and chemokines involved in immunological responses in viral CNS infections. We discuss in detail the link between specific cytokines and chemokines and leukocyte migration profiles. The thorough understanding of the complex and interrelated inflammatory mechanisms as well as identifying universal mediators promoting CNS inflammation is essential for the development of new diagnostic and treatment strategies.

Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

“…Furthermore, there is emerging evidence that the choroid plexuses are relevant entry sites for pathogens, such as bacteria, viruses, fungi and parasites into the CNS [31]. A number of pathogens, including Streptococcus suis, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, and Trypanosoma brucei, to just name a few, have been shown to use the choroidal epithelium as a CNS entry site (summarized in [131]).…”

“…A number of pathogens, including Streptococcus suis, Neisseria meningitidis, Haemophilus influenzae, Listeria monocytogenes, and Trypanosoma brucei, to just name a few, have been shown to use the choroidal epithelium as a CNS entry site (summarized in [131]). These pathogens may cross the epithelium directly via paracellular or transcellular routes or use Trojan horse approaches to breach the barrier [31]. The choroid plexus responds to these pathogens by eliciting a stereotype programmed innate inflammatory host response leading to an increased expression of cytokines and chemokines that trigger BCSFB breakdown and eventually to an increased CNS invasion of pathogenic inflammatory cells into the CNS.…”

Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

“…Western blot analysis of brain (D) and spinal cord (E) tissue from BALB/c mice treated with or without CQ after rOC43-ns2DelRluc inoculation. human respiratory syncytial virus, and human metapneumovirus, accompanied by neurological complications (Dahm et al, 2016;McGavern and Kang, 2011;Swanson and McGavern, 2015). Different mouse models have been established that are susceptible to these viruses (Cavallaro and Maassab, 1966;Liu et al, 2009;Rameix-Welti et al, 2014;Yu et al, 2014); however, these models do not develop severe CNS pathologies.…”

Molecular Pathogenicity of Enteroviruses Causing Neurological Disease

“…The BCSFB is a site of CNS immune surveillance, providing a more permissive barrier for immune cells to traverse, while the BBB is more resistant to the movement of both host cells and invasive pathogens (Ransohoff and Engelhardt, 2012). Some pathogens appear to be limited to crossing only the BBB, while others are able to traverse both the BBB and BCSFB by using various mechanisms (Dahm et al, 2016). Both CVB3 (Puccini et al, 2014) and echovirus 30 (Schneider et al, 2012) are able to directly infect the BCSFB.…”