Localizations of the Virus of Poliomyelitis in the Central Nervous System During the Preparalytic Period, After Intranasal Instillation

Abstract

The view that the virus of poliomyelitis enters the body through the nasal mucous membrane, first suggested by Flexner (1) in 1910 and consistently advocated by him and his associates since that time, appears now to be widely accepted. It is based on an impressive body of experimental evidence (2) showing that the nasal mucosa is unique among the body surfaces in permitting the ingress of virus without preliminary trauma. The relationship of this phenomenon to certain anatomical arrangements in the nose has been almost overlooked. Flexner in 1912 (3) commented on the fact that "the small olfactory filaments are advantageously placed to act as the means of transportation" (of the virus). It was not, however, until the discovery that poliomyelitis virus is propagated through the nerve cells and their axons, rather than through the blood, lymph or cerebrospinal fluid, that the nervous anatomy of the region took on unique significance in relation to poliomyelitis. Faber (2) has called attention to the importance of the unbroken connection of the olfactory nerves between the very surface of the nasal mucosa and the central nervous system proper. Hopkins (4) has shown that the terminal processes (olfactory hairs) of the olfactory cells are exposed to the air in the upper part of the nasal cavity, and the afferent axons of these cells pass through the olfactory nerves directly into the olfactory bulbs. No similar arrangement exists elsewhere on the body and no more * This study was aided in large part by a grant from the Rockefeller Fluid Research Fund of the School of Medicine of Stanford University. 933on May 11, 2018 jem.rupress.org Downloaded from http://doi.org/10. 1084/jem.57.6.933 Published Online: 1 June, 1933 934 LOCALIZATIONS 017 POLIOMYELITIS VIRUS ideal condition can be imagined for the entrance of a neurotropic virus deposited on the surface.Assuming that the nasal mucosa, or, more correctly, the olfactory cells and nerves, constitute the normal gateway through which poliomyelitis virus gains access to the central nervous system in man, the subsequent pathways by which it reaches the site of its maximum effects, the anterior horns of the spinal cord, still remain unknown. Only a few recorded attempts have been made to determine experimentally the various localizations of virus during the incubation period after intranasal inoculation, most of which have given negative results and apparently discouraged further study ? In 1912, Flexner and Clark (7) showed that 48 hours after swabbing the nasal mucosa of a monkey with virus, the olfactory bulb contained a demonstrable amount of virus, while none could be detected in the medulla or in the spinal cord. The earlier demonstration by Landsteiner and Levaditi (8) of virus in the olfactory bulbs 11 days after nasal inoculation (submucous injection) did not include the study of other possible points of infection in the central nervous system. In 1920, Flexner and Amoss (9) reported an experiment in which they left a cotton pledget soaked with virus in the nose o...

Murine Olfactory Bulb Interneurons Survive Infection with a Neurotropic Coronavirus

“…Many viruses replicate in the nasal cavity and the olfactory epithelium, which is distinct from the respiratory epithelium, and serves as an important portal of virus entry into the CNS (1). Thus, virus is first detected in the OB in experimental infections caused by neurotropic influenza A virus, West Nile virus, and others (2)(3)(4)(5)(6). In a similar vein, the OBLV strain of MHV replicates to high titers in the OB, with little evidence of spread elsewhere in the brains of immunocompetent mice (10,11,34).…”

“…V iral upper respiratory tract infection is a common cause of olfactory dysfunction, in part because the olfactory epithelium is located adjacent to the respiratory epithelium, the site of replication of multiple viruses that cause upper respiratory tract infection, and because olfactory neurons directly access the environment. Viruses take advantage of this direct connection with the olfactory bulb (OB) to enter the central nervous system (CNS) (1)(2)(3)(4)(5)(6). In the process of gaining access to the CNS, these viruses damage the olfactory epithelium and the olfactory bulb, leading to altered olfaction (7)(8)(9)(10)(11).…”

Potential neuroinvasive pathways of SARS‐CoV‐2: Deciphering the spectrum of neurological deficit seen in coronavirus disease‐2019 (COVID‐19)

“…[25][26][27][28]82,[83][84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100] The viral load resulting from rupture of the cells extending from the nasal mucosa to the olfactory bulb (A and B) via cribriform plate (A) can then be transported by the CSF (A, blue waves) to the adjacent and distant areas of the CNS. [88][89][90][91][92][93][94][95][96][97][98][99][100] As CSF is present in the subarachnoid space of the meninges directly supporting the olfactory nerves, the virus can reach the CNS without breaching the BBB. [101][102][103][104] [CNS, central nervous system; CSF, cerebrospinal fluid; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2]…”

The olfactory nerve: a shortcut for influenza and other viral diseases into the central nervous system

“…Poliovirus has been linked to CNS invasion via the olfactory nerve since 1933. In cynomolgus macaques, virus was demonstrated in the olfactory bulb and subsequently the olfactory tract and the rest of the CNS after intranasal inoculation [40,41]. Aerosol infection resulted in CNS invasion via the olfactory nerve in rhesus and cynomolgus macaques.…”