Table 1.

Viruses and their neurological impact

Viruses			Neurological impact		References
Classification		Primary infection/ latency
Herpesviridae	Herpes simplex virus 1 (HSV-1) Subfamily Alphaherpesvirinae	Epithelial cells of the oral and genital mucosa/ sensory ganglion neurons	AD	Periodic reactivations of the virus in the CNS – direct cytotoxicity and inflammatory damage in the CNS Formation of amyloid plaques and NFTs ApoE4 factor Oxidative stress	[7, 42, 49, 50]
			PD	Molecular mimicry with α-synuclein promoting its aggregation and consequent neuronal degeneration Increased TNF-α secretion inducing the death of dopaminergic neurons	[77, 78]
			Epilepsy	The encephalitis caused by the infection can lead to epilepsy. Inflammatory processes – increased neuronal excitability, contributing to epileptogenesis Neurotropism – damage to brain tissue and neurological sequelae	[111–113]
			GBS	Inflammatory nerve injury caused by cross-reactive antibodies against HSV-1 (anti-GQ1b antibodies) Alteration of ganglioside composition on the cell surface of neuronal and glial cells	[165–168]
	Cytomegalovirus (CMV) Human herpesvirus 5 (HHV-5) Subfamily Betaherpesvirinae	Mucosal epithelial cells and leukocytes/ peripheral blood CD14+ monocytes and bone marrow CD34+ cells	AD	Increase of pro-inflammatory cytokine IFN-γ in the CNS and peripheral tissue and association with the formation of NFTs	[55, 56]
			PD	Immunological reactivation Secretion of pro-inflammatory cytokines by dendritic cells Autoimmune response to neuromelanin	[80, 81]
			Epilepsy	The inflammatory process generated by the activation of microglia triggers the release of cytotoxic substances that lead to cell damage and induce necrosis.	[117]
			GBS	Expression of an immunogenic GM2-like epitope Autoantibodies against moesin production	[170, 171]
	Human herpesvirus 6 (HHV-6) Subfamily Betaherpesvirinae	B lymphocytes/ monocytes and macrophages, salivary glands, brain and kidneys	AD	The infection causes a cascade of events, such as decreased autophagy and the stress activation of the endoplasmic reticulum, which may trigger the generation of Aβ, causing tau protein hyperphosphorylation	[59]
			PD	Parainfectious cytotoxic changes, immunologically mediated mechanisms, or direct CNS invasion	[79]
			Epilepsy	Tropism for glial cells	[110]
			GBS	Important antigen-antibody reaction Polyclonal B cell activation Reactivation of a latent infection	[155, 156, 162, 172]
			MS	The latency established by HHV-6A in oligodendrocytes may contribute to, or even trigger an autoimmune reaction that leads to myelin impairment. Affecting the repairing process of myelin in the brain by infecting OPCs
	Epstein-Barr Virus (EBV) Subfamily Gammaherpesvirinae	Mucous epithelial cells/ B lymphocytes	PD	Molecular mimicry with α-synuclein promotes its aggregation and consequent neuronal degeneration.	[77]
			GBS	Polyclonal B cell activation Vascular damage: direct invasion of endothelial cells or immune-complex-mediated	[162, 175]
			MS	Stimulates the expression of HERVs that contribute to the development of MS EBV replication in CNS chronically activates the immune system, recruiting microglia and astrocytes, which become destructive and neurotoxic. EBV-infected B-cells are not able to protect proteolysis-sensitive immunodominant MOG from the cytotoxic effects of T cells, leading to impaired myelination of CNS nerves and damage to the structural integrity of the myelin sheath. Primary EBV infection induces an increase in BBB permeability.	[143–146, 148–150]
Orthomyxoviridae	Influenza A virus subtype H5N1 (H5N1)	Respiratory tract Infects the CNS (mice)	PD	The direct or indirect inflammatory response in the CNS with degeneration of dopaminergic neurons Neuronal loss in SNpc	[8, 71]
			GBS	Anti-glycolipid antibody production (infection) Autoimmune responses (vaccine) Increases the permeability of BBB by endotoxin Formation of sialic acid-HA complexes that mimic GM-1	[176]
Flaviviridae	Hepatitis C virus (HCV)	Peripheral blood lymphocytes and monocytes	AD	Direct damage to the CNS by activation of neurotoxic cytokines (TNF-α, IL-6) Indirect damage by chronic systemic inflammation that may affect the CNS	[60, 61]
			PD	Positive regulation of chemokines with dopaminergic neurotoxicity	[83]
			GBS	Reactivation of the virus or its enhanced replication Immune complex deposition along the vascular endothelium Anti- MAG antibody production	[162, 179, 181]
	Dengue virus (DENV)	Dendritic cells, monocytes, and macrophages	Epilepsy	DENV infection may lead to meningitis, encephalitis, and encephalomyelitis.	[119]
			GBS	Pro-inflammatory cytokine production Cross-reactivation of antibodies with endothelial cells (anti-NS1) and platelets	[182–184]
Retroviridae	Human immunodeficiency virus (HIV)	Dendritic cells, followed by T-helper cell (CD4 + T)/ memory T cells	PD	Accumulation of α-synuclein in SNpc, presence of HIV in inflammatory infiltrates, glial cells and in the substantia nigra Deregulation of protein levels associated with PD (DJ1 and LRRK2)	[87, 88]
			Epilepsy	Secondary infections of the CNS and metabolic disorders Formation of autoantibodies, causing neuronal death, with increased exocytosis of glutamate and decreased recapture, which leads to the activation of calcium channels and consequent neuronal hyperexcitability	[125–128]
			GBS	Direct action on the nerves by neurotropic strains or autoimmune mechanisms Alteration of BBB integrity by Tat, gp120, and Nef Increase of TNFα	[185, 188, 189]
Coronaviridae	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)	Cells in the respiratory tract, most likely type II pneumocytes in the lungs, goblet secretory cells in the nasal passages, and the absorptive enterocytes in the intestines Suggested neurotropism to brain cells (due to high expression of ACE2 receptors in this organ)	*SARS-CoV-2 infection may trigger encephalitis, seizure (or focal status epilepticus), meningitis, acute cerebrovascular diseases, impaired consciousness, skeletal muscle symptoms, agitation, confusion, and signs of corticospinal tract dysfunction *This infection may trigger immune-mediated processes, which may lead to GBS. *SARS-CoV-2 infection is likely to trigger demyelination similar to MS. *SARS-CoV-2 causes a cytokine storm, which may trigger acute necrotizing hemorrhagic encephalopathy and BBB disruption.		[195-203, 205, 211-213]

AD, Alzheimer’s disease; PD, Parkinson’s disease; GBS, Guillain-Barré Syndrome; MS, multiple sclerosis; HERVs, human endogenous retrovirus; MOG, myelin oligodendrocyte glycoprotein; OPCs, oligodendrocyte progenitor cells; BBB, blood-brain barrier; CNS, central nervous system; NFTs, neurofibrillary tangles; apoE4, apolipoprotein E4; TNFα, tumor necrosis factor alpha; IFN-γ, interferon gamma; GM-1, gangliosidosis 1; IL-6, interleukin 6; anti-MAG, anti-myelin-associated glycoprotein; SNpc, substantia nigra pars compacta; Tat, transativator of transcription; Nef, negative regulatory factor

^*All neurological effects of SARS-CoV-2 infection described in the table are based on isolated cases or studies based on a small group of patients infected. Further investigation must be conducted to clarify the neurological effects of SARS-CoV-2 infection. Also, long-term monitoring of patients is necessary to verify its impact on neuronal function and its possible impact on the development of neurological diseases.

Source: authors