Non-Cytolytic Enteroviruses May Play a Fundamental Role in ME/CFS Dr John Chia, Prof Nora Chapman, Prof Steven Tracy and others think that, in addition to normal lytic enteroviruses, non-cytolytic enteroviruses (aka: non-cytopathic enteroviruses) may also be playing a fundamental role in ME/CFS. For one thing, non-cytolytic live inside human cells, as an intracellular infection. A normal enterovirus infection begins with the lytic form of the virus that you catch. However, once inside your body, lytic enteroviruses can convert into non-cytolytic enteroviruses, and the latter are very different entities, with very different life cycles. Non-cytolytic enteroviruses have been associated with ME/CFS,† as well as a number of other diseases such as type 1 diabetes,† myocarditis,† cardiomyopathy (in a murine model),† and chronic inflammatory myopathy.† Non-cytolytic enteroviruses may conceivably be the primary casual agent in these diseases. Difference Between Lytic and Non-Cytolytic Enteroviruses As its name suggests, in the life cycle of a regular lytic enterovirus, the virus enters a human cell, replicates itself thousands of times inside the cell, and then ruptures and kill the cell (lysis) so that these thousands of replicated viruses can escape the cell, and go onto to infect more cells. By contrast, non-cytolytic enteroviruses live within human cells on a long term basis, and do not lyse (do not rupture and kill) the cell they live in, and do not burst out of the cell as lytic viruses do. And even they were able to burst out of the cell, these non-cytolytic viruses would not survive for long outside the cell, because non-cytolytic enteroviruses do not have an outer shell (capsid) to protect them. So you might think that a non-cytolytic enterovirus infection would not spread any further than the cells it lives in. However, a new study uncovers a mechanism by which non-cytolytic enteroviruses may spread in the body tissues. How Non-Cytolytic Enteroviruses Might Spread in the Body Tissues The following study reveals a mechanism by which non-cytolytic enteroviruses may be able to transmit copies of themselves into adjacent cells, thus facilitating their spread to and infection of more cells: Coxsackievirus B3-Induced Cellular Protrusions: Structural Characteristics and Functional Competence This study shows that in coxsackievirus B infected cells, this virus seems to be able to induce cellular protrusions to grow out of the cell. Cellular protrusions are tentacle-like filaments that issue from the cell, and are a normal part of cellular function. Cellular protrusions are used by the cell when it wants to gain traction and pull itself along in the tissue spaces. However, the authors posit that these protrusions may be the means by which non-cytolytic coxsackievirus B infections are able to transmit into adjacent cells: the authors suggest that non-cytolytic viruses may induce these cellular protrusions to create a bridge to adjacent cells, which they then cross, in order to infect the nearby cells. So even though non-cytolytic viruses do not have a protective outer shell, they may still be able to slowly spread to and infect more cells. There is actually a time-lapse video attached to this study in which you can watch the putative spread of non-cytolytic coxsackievirus B by means of the cellular protrusions it induces; this video can be downloaded from here (see supplemental file 1). In the video, the infected cells shown on the left hand side of the picture are seen sprouting the cellular protrusions that may be spreading the non-cytolytic viral infection from cell to cell. The cells shown on the right hand side are uninfected cells, used as a control. Here is a snapshot of this video, showing the tentacle-like cellular protrusions running from cell to cell: Coxsackie B virus infected cells showing cellular protrusions (thin filaments) running from cell to cell. These protrusions may transmit the non-cytolytic Coxsackie B virus to adjacent cells. More Information About Non-Cytolytic Enteroviruses Human Enteroviruses and Chronic Infectious Disease. Steven Tracy and Nora M. Chapman. Replication Defective Enterovirus Infections: Implications for Type I Diabetes. Nora M. Chapman. Normal lytic enteroviruses are also called: cytolytic enteroviruses, cytopathic enteroviruses, or wild-type viruses. Non-cytolytic enteroviruses are also called: non-cytopathic enteroviruses, defective enteroviruses, and terminally-deleted enteroviruses. Non-cytolytic enteroviruses may be detected by sensitive RT-PCR, and by immunohistochemistry (ref: see page 22 of this document). Note that enteroviruses are not the only type of virus that develop into non-cytolytic infections. Google search on the terms: non-cytolytic virus, non-cytopathic virus, defective virus and terminally-deleted virus for more info on non-cytolytic viral infections in general.