Do You Hear The Music? Viral Evolution

destiNATIONS

Viral Synaptic Transmission

Three routes of viral entry into the brain have been identified: direct infection of the cells that comprise the blood–brain barrier and blood–cerebrospinal fluid barrier, infection of cells that are licensed to cross these barriers, and transneuronal migration across synapses from the periphery to the CNS.

Some viruses that are cytopathic in renewable cell types can switch to a non-productive, non-syncytia-forming mode of spread when infecting neurons, promoting neuron survival.

Long-lasting viral infections within the brain may be classified based on the state of the viral genome, its ability to produce infectious progeny and whether such progeny can infect other hosts.

Neurotropic viral infections pose unique challenges for the host, including the need to detect antigens within the CNS, the requirement for T lymphocytes to engage with neurons that express negligible levels of the proteins that are typically present on target cells, and the need to mitigate the risk of neuroinflammation and widespread loss of generally non-renewable neurons.

The identification of lymphatic drainage portals from the CNS into deep cervical lymph nodes and the presence of a fluid gradient that flushes the brain of extracellular proteins have helped to define how antigens leave the brain to educate the host response in local lymph nodes.

The host response to a viral infection may be tailored to promote survival of infected neurons but to destroy similarly infected epithelial or endothelial cells.

Non-lytic clearance of neuronal infections may allow for persistence of RNA viruses that induce pathogenesis long after primary exposure.

I think Emma overdosed on the wiffle sticks again.

New technologies in neuroimaging are making it easier to see neurons and neural paths. Some of the neurons in this mouse cerebellum, for example, were infected with a virus engineered to produce a green fluorescent protein. Once this virus entered the neuron, it replicated and traveled along the neuron and dendrites to the synapses, where it jumped to connecting neurons. Other neurons were stained with blue dye, allowing the researchers to see the brain’s different structures, thus providing a sort of cellular topography against which to reference the movements of the fluorescing virus. The researchers then used a fluorescent microscope to find the traveling viruses and to observe the dispersal of green to pinpoint synaptic connections and see how information flows through the brain.

The investigators expected the synaptic connections infected with the engineered virus to be localized in the areas of the brain involved in motor control, but instead they found the virus had traveled to connections beyond the cerebellum. The virus had spread to parts of the brain associated with higher-level cognitive function.

Viral infections of the CNS that injure or destroy specific populations of brain cells are frequently associated with behavioral disturbances.

These events occur either directly due to virus replication or indirectly as a result of the host immune response against the infectious agent. Neurotropic viruses can also persist in the CNS and, in the absence of cell destruction or inflammation, cause defects in goal-oriented behavior.

Therefore, viruses may contribute to human CNS disorders whose etiology remains elusive. The finding of virally mediated impairment in neuronal function in the absence of cell destruction raises the possibility that noncytolytic viruses that persistently infect neurons may contribute to many human CNS disorders whose etiology is unknown.

Your Brain on Covid - Long Term Implications - Synaptic Infection - Neurological Disorders - Universal Permanant Alterations in Those Who “Recovered”

Virus infection causes alterations in expression of synaptic regulatory genes combined with changes in cognitive and emotional behaviors.

Viral infections of the CNS that injure or destroy specific populations of brain cells are frequently associated with behavioral disturbances. These events occur either directly due to virus replication or indirectly as a result of the host immune response against the infectious agent. Neurotropic viruses can also persist in the CNS and, in the absence of cell destruction or inflammation, cause defects in goal-oriented behavior. Therefore, viruses may contribute to human CNS disorders whose etiology remains elusive. The finding of virally mediated impairment in neuronal function in the absence of cell destruction raises the possibility that noncytolytic viruses that persistently infect neurons may contribute to many human CNS disorders whose etiology is unknown.

SARS-CoV-2 can also infect the brain by migrating from the general circulation to the cerebral microcirculation via endothelial cells which express ACE2[5].In a recent case study published by Poyiadji et al.[25], they described an acute hemorrhagic necrotizing encephalopathy that was directly attributed to SARS-CoV-2 infection and the concurrent cytokine storm induced upon infection[25,26]. Beyond isolated cases of overt severe neurological pathologies, 45% of severe cases exhibited neurologic symptoms[3], increasing the likelihood that potential complications arising from severe SARS-CoV-2 infections may have a strong neurologic component that has yet to be described and characterized. Human coronavirus OC43 has been demonstrated to be transmitted in mice both passive diffusion of released viral particles and axonal transport[27].

[link to nnjournal.net (secure)]

The current global pandemic outbreak of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known for its viral tropism to the lungs, which in severe cases can lead to the fatal respiratory failure of patients who have contracted the disease. SARS-CoV-2 and SARS-CoV viruses have a 70%-80% homology and both enter the body through the same receptor, angiotensin converting enzyme 2 (ACE2)[1].

In addition to their genetic homology, the pathology that the two viruses exhibit in the clinic are highly similar[2]. In a recent report from Wuhan, China, Mao and colleagues showed that in addition to respiratory symptoms including pneumonia and acute respiratory distress syndrome (ARDS), out of 214 hospitalized COVID-19 patients 78 (36.4%) showed neurological manifestations such as cerebrovascular diseases (5.7%), impaired consciousness (14.8%), and skeletal muscle injury (19.3%)[3]. Six percent of COVID-19 patients have been reported to show symptoms of stroke and 15% were reported to show encephalopathy[4]. A number of symptoms such as dizziness, headache, loss of taste and smell, impaired consciousness, seizures, and nerve pain suggest a neurological connection to this viral infection.


Neuromechanisms of SARS-CoV-2: A Review

[link to www.frontiersin.org (secure)]