Entry of coronavirus into primate CNS following peripheral infection

Abstract

A previous report demonstrated that intracerebrally inoculated coronavirus produced CNS disease in two species of primates (Murray RS, Cai G-Y, Hoel K, et al., Virol 1992; 188: 274-84). We were therefore interested in testing the potential of coronaviruses to infect primate CNS tissue following peripheral inoculation. Four Owl monkeys (Aotus trivirgatus) were inoculated intranasally and ocularly and four were inoculated intravenously with coronavirus JHM OMp1 (Murray RS, Cai G-Y, Hoel K, et al., Virol 1992; 188: 274-84). Two intranasally and two intravenously inoculated animals received a second intravenous inoculum at 153 days post-infection. The animals were sacrificed 16, 35, 194, and 215 days post-infection. Tissue sections from brain and spinal cord were screened for viral products by in sity hybridization and immunostaining. Virus RNA and/or antigen was detected in the brains of all animals and the distribution corresponded to areas of inflammation and edema. Viral products were predominantly found in blood vessels and perivascular regions, suggesting hematogenous spread with entry into the central nervous system through endothelium.

Neuroinvasion by Human Respiratory Coronaviruses

“…Some murine coronaviruses are neurotropic, neuroinvasive, and neurovirulent in rodents (27,58) and in nonhuman primates (11,38), inducing in some cases an MS-like demyelinating disease. Our goal is to investigate the possible neurotropism, neuroinvasion, and neurovirulence of the related HCoV, which have so far only been definitively associated with respiratory infections, with occasional reports of associations with diarrhea and neurologic diseases, mainly MS (39).…”

“…Its outcome is influenced by genetics of the host and virus, dose and route of inoculation, and host age and immunological status at the time of infection (58). Neurotropic MHV strains could invade the CNS following an intranasal inoculation in mice (34) and could also gain access to the CNS via the hematogenous and/or lymphatic systems in mice (7) and in primates (11). Given that HCoV are respiratory viruses, they might also invade the CNS following a primary infection of the upper respiratory tract.…”

¿Es esperable que haya cuadros neurológicos por la pandemia por SARS-CoV-2?

“…El MHV-CoA es un virus que afecta al ratón 57 y no al humano que induce trastornos neurológicos 58,59 , y ello ha posibilitado la creación de un modelo experimental para estudiar el papel de los CoV en el SNC. Las cepas neurotrópicas de MHV pueden invadir el SNC por inoculación intranasal en ratones 60 y también por vía sanguínea, y ello se ha observado también en primates 61 . El paso por la barrera hematoencefalica se ha relacionado con la producción de interferón-beta por las células epiteliales de la microcirculación cerebral 62 .…”

Immunopathological aspects of coronavirus infections

“…On the other hand, there are reports of coronavirus RNA or protein being detected in brain tissue in some MS cases [59,88]. Furthermore, murine coronaviruses can induce encephalomyelitis in primates [4,60]. There have been numerous attempts to incriminate viruses as an agent which triggers MS. No epidemiological evidence indicates that coronaviruses are involved in this disease.…”