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Non-Cytolytic Enterovirus May Play a Fundamental Role in ME/CFS
In the chronic enterovirus infections found in ME/CFS, there is an unusual form of this virus called a non-cytolytic enterovirus. It is believed that this non-cytolytic enterovirus may be a major cause of ME/CFS.
Unlike regular enteroviruses, non-cytolytic enteroviruses do not produce any lytic virus. Non-cytolytic enteroviruses live inside human cells as a long-term intracellular infection. Coxsackievirus B (CVB) and echovirus are two enteroviruses known to be able to create such chronic non-cytolytic infections.
Non-cytolytic coxsackievirus B is found in the muscles and intestines of ME/CFS patients, the heart muscle in chronic CVB myocarditis, in the muscles in chronic inflammatory myopathy (an inflammatory muscle disease), and has been shown to infect the murine pancreas, which is relevant in udnertanding type 1 diabetes. Refs: 1, 2, 3, 4. This non-cytolytic CVB may be the major casual factor in these diseases.
Coxsackievirus B or echovirus infection begins with the regular form of the virus that you catch. However, once inside the body, a regular enterovirus can transform into a non-cytolytic virus, and then take up long-term residence in your cells, forming a chronic intracellular infection that your immune system finds hard to clear.
Nora Chapman, Steven Tracy, John Chia, Patricia Tam and Ronald Messner and others pioneered investigation of chronic non-cytolytic enterovirus infections, and Chapman's research led to the discovery and understanding of the molecular mechanism behind non-cytolytic infection.
Lytic and Non-Cytolytic Enterovirus
In the life cycle of a regular (lytic) enterovirus, the virus enters a human cell, replicates itself thousands of times, then ruptures and kills the cell by lysis (lysis means cell rupture) so that the thousands of newly created viruses can escape, and go onto to infect more cells.
By contrast, non-cytolytic enteroviruses live within human cells on a long term basis. They do not create any lytic enteroviruses, and they do not lyse the cell they live in (they do not kill the cell). They remain in the cell on a long term basis as a slow "smoldering" infections.
Non-cytolytic viruses may nevertheless cause cellular dysfunction due to their presence in the cell (they produce viral proteins), and provoke an immune response, which may lead to disease.
How Non-Cytolytic Enteroviruses May Spread
This study demonstrates a possible mechanism by which non-cytolytic enteroviruses may be able to spread into adjacent cells.
This study found that in CVB-infected cells, the virus seems to be able to create filament-like cellular protrusions that grow out of the cell, bridging to adjacent cells.
Cellular protrusions are a normal part of cellular function: they are created by the cell when it wants to gain traction and pull itself along in the tissues — this is basically how cells can move.
However, the authors suggest that these protrusions may be used by CVB in order to transmit the infection into adjacent cells. In other words, enterovirus may induce cellular protrusions to create a bridge to adjacent cells, which they then cross.
There is a time-lapse video (supplemental file 1) in this study in which shows the creation and movement of these cellular protrusions produced in a CVB infection:
In the above video, cells infected with Coxsackie B virus are shown on the left, and are seen sprouting the black thin filament-like cellular protrusions, which may carry the non-cytolytic infection cell to cell. The cells on the right are uninfected controls.
Here is a snapshot from this video, showing the cellular protrusions (black filaments) running from cell to cell:
Coxsackie B virus infected cells showing cellular protrusions
(thin black filaments) running from cell to cell. These protrusions may
transmit the non-cytolytic Coxsackie B virus from cell to cell.
Uninfected cells do not display such protrusions.
Some background info on the nature of cellular protrusions (click button):
More Info On Non-Cytolytic Enteroviruses
Non-cytolytic enterovirus — MEpedia.
Nora Chapman: How does a lytic enterovirus infection persist and cause chronic disease?
Human Enteroviruses and Chronic Infectious Disease by Prof Steven Tracy and Prof Nora M. Chapman.
Replication Defective Enterovirus Infections: Implications for Type I Diabetes by Prof Nora M. Chapman.
Non-cytolytic enteroviruses are also called:
In the chronic enterovirus infections found in ME/CFS, there is an unusual form of this virus called a non-cytolytic enterovirus. It is believed that this non-cytolytic enterovirus may be a major cause of ME/CFS.
Unlike regular enteroviruses, non-cytolytic enteroviruses do not produce any lytic virus. Non-cytolytic enteroviruses live inside human cells as a long-term intracellular infection. Coxsackievirus B (CVB) and echovirus are two enteroviruses known to be able to create such chronic non-cytolytic infections.
Non-cytolytic coxsackievirus B is found in the muscles and intestines of ME/CFS patients, the heart muscle in chronic CVB myocarditis, in the muscles in chronic inflammatory myopathy (an inflammatory muscle disease), and has been shown to infect the murine pancreas, which is relevant in udnertanding type 1 diabetes. Refs: 1, 2, 3, 4. This non-cytolytic CVB may be the major casual factor in these diseases.
Coxsackievirus B or echovirus infection begins with the regular form of the virus that you catch. However, once inside the body, a regular enterovirus can transform into a non-cytolytic virus, and then take up long-term residence in your cells, forming a chronic intracellular infection that your immune system finds hard to clear.
Nora Chapman, Steven Tracy, John Chia, Patricia Tam and Ronald Messner and others pioneered investigation of chronic non-cytolytic enterovirus infections, and Chapman's research led to the discovery and understanding of the molecular mechanism behind non-cytolytic infection.
Lytic and Non-Cytolytic Enterovirus
In the life cycle of a regular (lytic) enterovirus, the virus enters a human cell, replicates itself thousands of times, then ruptures and kills the cell by lysis (lysis means cell rupture) so that the thousands of newly created viruses can escape, and go onto to infect more cells.
By contrast, non-cytolytic enteroviruses live within human cells on a long term basis. They do not create any lytic enteroviruses, and they do not lyse the cell they live in (they do not kill the cell). They remain in the cell on a long term basis as a slow "smoldering" infections.
Non-cytolytic viruses may nevertheless cause cellular dysfunction due to their presence in the cell (they produce viral proteins), and provoke an immune response, which may lead to disease.
How Non-Cytolytic Enteroviruses May Spread
This study demonstrates a possible mechanism by which non-cytolytic enteroviruses may be able to spread into adjacent cells.
This study found that in CVB-infected cells, the virus seems to be able to create filament-like cellular protrusions that grow out of the cell, bridging to adjacent cells.
Cellular protrusions are a normal part of cellular function: they are created by the cell when it wants to gain traction and pull itself along in the tissues — this is basically how cells can move.
However, the authors suggest that these protrusions may be used by CVB in order to transmit the infection into adjacent cells. In other words, enterovirus may induce cellular protrusions to create a bridge to adjacent cells, which they then cross.
There is a time-lapse video (supplemental file 1) in this study in which shows the creation and movement of these cellular protrusions produced in a CVB infection:
In the above video, cells infected with Coxsackie B virus are shown on the left, and are seen sprouting the black thin filament-like cellular protrusions, which may carry the non-cytolytic infection cell to cell. The cells on the right are uninfected controls.
Here is a snapshot from this video, showing the cellular protrusions (black filaments) running from cell to cell:
Coxsackie B virus infected cells showing cellular protrusions
(thin black filaments) running from cell to cell. These protrusions may
transmit the non-cytolytic Coxsackie B virus from cell to cell.
Uninfected cells do not display such protrusions.
Some background info on the nature of cellular protrusions (click button):
Cellular protrusions are like the legs of the cell, as they allow a cell to move to specific locations in the tissues. Cellular protrusions comprise a portion of the normal membrane of the cell that has been elongated to form a long tendril shape.
There are two types of cellular protrusion:
Lamellipodia are broad and flat cellular protrusions which sprout out of the cell in the direction of intended movement of the cell, adhering to surfaces ahead, thus allowing the cell to gain an anchor point and traction, and pull itself along in that direction.
Filopodia are long and thin cellular protrusions, and act as the guiding "eyes" of the cell, extending ahead of the cell and exploring the immediate environment of the cell, sensing guiding cues, and directing the movement of the cell.
Source: The mechanics of Cell Protrusion
There are two types of cellular protrusion:
Lamellipodia are broad and flat cellular protrusions which sprout out of the cell in the direction of intended movement of the cell, adhering to surfaces ahead, thus allowing the cell to gain an anchor point and traction, and pull itself along in that direction.
Filopodia are long and thin cellular protrusions, and act as the guiding "eyes" of the cell, extending ahead of the cell and exploring the immediate environment of the cell, sensing guiding cues, and directing the movement of the cell.
Source: The mechanics of Cell Protrusion
More Info On Non-Cytolytic Enteroviruses
Non-cytolytic enterovirus — MEpedia.
Nora Chapman: How does a lytic enterovirus infection persist and cause chronic disease?
Human Enteroviruses and Chronic Infectious Disease by Prof Steven Tracy and Prof Nora M. Chapman.
Replication Defective Enterovirus Infections: Implications for Type I Diabetes by Prof Nora M. Chapman.
Non-cytolytic enteroviruses are also called:
- Non-cytopathic enteroviruses
- Defective enteroviruses
- Terminally-deleted enteroviruses
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