Epstein-Barr virus.

Respiratory viruses infect the human upper respiratory tract, mostly causing mild diseases. However, in vulnerable populations, such as newborns, infants, the elderly and immune-compromised individuals, these opportunistic pathogens can also affect the lower respiratory tract, causing a more severe disease (e.g., pneumonia). Respiratory viruses can also exacerbate asthma and lead to various types of respiratory distress syndromes. Furthermore, as they can adapt fast and cross the species barrier, some of these pathogens, like influenza A and SARS-CoV, have occasionally caused epidemics or pandemics, and were associated with more serious clinical diseases and even mortality. For a few decades now, data reported in the scientific literature has also demonstrated that several respiratory viruses have neuroinvasive capacities, since they can spread from the respiratory tract to the central nervous system (CNS). Viruses infecting human CNS cells could then cause different types of encephalopathy, including encephalitis, and long-term neurological diseases. Like other well-recognized neuroinvasive human viruses, respiratory viruses may damage the CNS as a result of misdirected host immune responses that could be associated with autoimmunity in susceptible individuals (virus-induced neuro-immunopathology) and/or viral replication, which directly causes damage to CNS cells (virus-induced neuropathology). The etiological agent of several neurological disorders remains unidentified. Opportunistic human respiratory pathogens could be associated with the triggering or the exacerbation of these disorders whose etiology remains poorly understood. Herein, we present a global portrait of some of the most prevalent or emerging human respiratory viruses that have been associated with possible pathogenic processes in CNS infection, with a special emphasis on human coronaviruses.

Human Coronaviruses and Other Respiratory Viruses: Underestimated Opportunistic Pathogens of the Central Nervous System?

Central Nervous System (CNS) infections are one of the most critical problems in public health, as frequently patients exhibit neurologic sequelae. Usually, CNS pathologies are caused by known neurotropic viruses such as measles virus (MV), herpes virus and human immunodeficiency virus (HIV), among others. However, nowadays respiratory viruses have placed themselves as relevant agents responsible for CNS pathologies. Among these neuropathological viruses are the human respiratory syncytial virus (hRSV), the influenza virus (IV), the coronavirus (CoV) and the human metapneumovirus (hMPV). These viral agents are leading causes of acute respiratory infections every year affecting mainly children under 5 years old and also the elderly. Up to date, several reports have described the association between respiratory viral infections with neurological symptoms. The most frequent clinical manifestations described in these patients are febrile or afebrile seizures, status epilepticus, encephalopathies and encephalitis. All these viruses have been found in cerebrospinal fluid (CSF), which suggests that all these pathogens, once in the lungs, can spread throughout the body and eventually reach the CNS. The current knowledge about the mechanisms and routes used by these neuro-invasive viruses remains scarce. In this review article, we describe the most recent findings associated to neurologic complications, along with data about the possible invasion routes of these viruses in humans and their various effects on the CNS, as studied in animal models.

/pdf/neurologic-alterations-due-to-respiratory-virus-infections-39yee5b2hl.pdf

Neurologic Alterations Due to Respiratory Virus Infections

The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood-brain barrier.

Immune privilege of the central nervous system (CNS) has been ascribed to the presence of a blood-brain barrier and the lack of lymphatic vessels within the CNS parenchyma. However, immune reactions occur within the CNS and it is clear that the CNS has a unique relationship with the immune system. Recent developments in high-resolution imaging techniques have prompted a reassessment of the relationships between the CNS and the immune system. This review will take these developments into account in describing our present understanding of the anatomical connections of the CNS fluid drainage pathways towards regional lymph nodes and our current concept of immune cell trafficking into the CNS during immunosurveillance and neuroinflammation. Cerebrospinal fluid (CSF) and interstitial fluid are the two major components that drain from the CNS to regional lymph nodes. CSF drains via lymphatic vessels and appears to carry antigen-presenting cells. Interstitial fluid from the CNS parenchyma, on the other hand, drains to lymph nodes via narrow and restricted basement membrane pathways within the walls of cerebral capillaries and arteries that do not allow traffic of antigen-presenting cells. Lymphocytes targeting the CNS enter by a two-step process entailing receptor-mediated crossing of vascular endothelium and enzyme-mediated penetration of the glia limitans that covers the CNS. The contribution of the pathways into and out of the CNS as initiators or contributors to neurological disorders, such as multiple sclerosis and Alzheimer's disease, will be discussed. Furthermore, we propose a clear nomenclature allowing improved precision when describing the CNS-specific communication pathways with the immune system.

/pdf/vascular-glial-and-lymphatic-immune-gateways-of-the-central-2hz7aky7cp.pdf

Vascular, glial, and lymphatic immune gateways of the central nervous system

Correction to: The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis

Henriette Rudolph1*, Armelle Klopstein2 and Britta Engelhardt2 1Pediatric Infectious Diseases, University Children’s Hospital, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany 2Theodor Kocher Institute, University of Bern, 3012 Bern, Germany *Corresponding author: Henriette Rudolph, Pediatric Infectious Diseases, University Children’s Hospital, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, E-mail: Henriette.Rudolph@medma.uni-heidelberg.de

Stalling Instead of Crawling Allows CD8+ T cells to Cross the Blood-BrainBarrier

Die bakterielle Meningitis und die virale Enzephalitis sind die infektiösen Erkrankungen des Zentralnervensystems (ZNS), die meist mit schwerwiegenden Folgeerscheinungen bis hin zum Tod einhergehen. Trotz Fortschritten in der Prävention durch Impfungen ist die globale Krankheitslast der bakteriellen Meningitis enorm. Die Inzidenz der viralen Enzephalitis im Kindesalter war vor der durch die „coronavirus disease 2019“ (COVID-19) ausgelösten Pandemie zunehmend. Dies hängt mit der wachsenden Verbreitung von „emerging pathogens“ wie dem Enterovirus-A71 und dem West-Nil-Virus in den hiesigen Breitengraden zusammen, aber auch mit der häufigeren Anwendung von Immunsuppressiva und der häufigeren Durchführung von Stammzelltransplantationen im Kindesalter. In der vorliegenden Übersichtsarbeit werden Häufigkeit und klinische Zeichen von infektiösen ZNS-Erkrankungen zusammengefasst und die aktuellen Therapieempfehlungen dargestellt. 

/pdf/severe-courses-of-meningitis-and-encephalitis-in-children-2uifwu3s.pdf

Henriette Rudolph

Papers

Correction to: The choroid plexus acts as an immune cell reservoir and brain entry site in experimental autoimmune encephalomyelitis

Stalling Instead of Crawling Allows CD8+ T cells to Cross the Blood-BrainBarrier

[Severe courses of meningitis and encephalitis in children and adolescents].