Tag: neurotropic viral infection

Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis

Abstract:

Billions of years of co-evolution has made mitochondria central to the eukaryotic cell and organism life playing the role of cellular power plants, as indeed they are involved in most, if not all, important regulatory pathways. Neurological disorders depending on impaired mitochondrial function or homeostasis can be caused by the misregulation of “endogenous players”, such as nuclear or cytoplasmic regulators, which have been treated elsewhere. In this review, we focus on how exogenous agents, i.e., viral pathogens, or unbalanced microbiota in the gut-brain axis can also endanger mitochondrial dynamics in the central nervous system (CNS).

Neurotropic viruses such as Herpes, Rabies, West-Nile, and Polioviruses seem to hijack neuronal transport networks, commandeering the proteins that mitochondria typically use to move along neurites. However, several neurological complications are also associated to infections by pandemic viruses, such as Influenza A virus and SARS-CoV-2 coronavirus, representing a relevant risk associated to seasonal flu, coronavirus disease-19 (COVID-19) and “Long-COVID”.

Emerging evidence is depicting the gut microbiota as a source of signals, transmitted via sensory neurons innervating the gut, able to influence brain structure and function, including cognitive functions. Therefore, the direct connection between intestinal microbiota and mitochondrial functions might concur with the onset, progression, and severity of CNS diseases.

Source: Righetto I, Gasparotto M, Casalino L, Vacca M, Filippini F. Exogenous Players in Mitochondria-Related CNS Disorders: Viral Pathogens and Unbalanced Microbiota in the Gut-Brain Axis. Biomolecules. 2023 Jan 13;13(1):169. doi: 10.3390/biom13010169. PMID: 36671555; PMCID: PMC9855674. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9855674/ (Full text)

Tunneling nanotubes provide a route for SARS-CoV-2 spreading

Abstract:

Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain.

We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo-electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells.

Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells.

Source: Pepe A, Pietropaoli S, Vos M, Barba-Spaeth G, Zurzolo C. Tunneling nanotubes provide a route for SARS-CoV-2 spreading. Sci Adv. 2022 Jul 22;8(29):eabo0171. doi: 10.1126/sciadv.abo0171. Epub 2022 Jul 20. PMID: 35857849; PMCID: PMC9299553.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299553/ (Full text)

Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome

Abstract:

Borna disease virus (BDV) is a neurotropic, as yet unclassified, non-segmented, negative-sense, single-strand RNA virus. Natural infection with this virus has been reported to occur in horses and sheep. In addition, antibodies to BDV in plasma or BDV RNA in peripheral blood mononuclear cells (PBMCs) were also found in patients with neuropsychiatric diseases. We describe here the possible link between the patients with chronic fatigue syndrome (CFS) and infection with BDV.

 

Source: Kitani T, Kuratsune H, Fuke I, Nakamura Y, Nakaya T, Asahi S, Tobiume M, Yamaguti K, Machii T, Inagi R, Yamanishi K, Ikuta K. Possible correlation between Borna disease virus infection and Japanese patients with chronic fatigue syndrome. Microbiol Immunol. 1996;40(6):459-62. http://www.ncbi.nlm.nih.gov/pubmed/8839433

 

Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome

Abstract:

Abnormalities in the regulation of the hypothalamo-pituitary-adrenal (HPA) axis are a well recognised feature of endogenous depression. The mechanism underlying this phenomenon remains obscure although there is strong evidence suggesting excessive CRH activity at the level of the hypothalamus.

We propose a novel hypothesis in which we suggest that the aetiological antecent to CRH hyperactivity is cytokine activation in the brain. It is now well established both that interleukins -1 and -6 are produced in a number of central loci and that cytokines are potent stimulators of the HPA axis.

Hence, we suggest that activation of IL-1 and IL-6 by specific mechanisms (such as neurotropic viral infection) in combination with the consequent CRH-41 stimulation, may (via their known biological effects) underly many of the features found in major depression and other related disorders, particularly where chronic fatigue is a prominent part of the symptom complex.

This theory has considerable heuristic value and suggests a number of experimental stratagems which may employed in order to confirm or reject it.

 

Source: Ur E, White PD, Grossman A. Hypothesis: cytokines may be activated to cause depressive illness and chronic fatigue syndrome. Eur Arch Psychiatry Clin Neurosci. 1992;241(5):317-22. http://www.ncbi.nlm.nih.gov/pubmed/1606197