The Enterovirus Theory of Disease Etiology in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: A Critical Review

Figure 1. Representative enterovirus genome structure with emphasis on 5′UTR Domain I and genome replication. (A) Graphical depiction of EV genome as well as proteolytic processing to produce all structural and non-structural proteins. Number ranges indicate nucleotide positions for domains 1–7 in the 5′UTR of CVB4. (B) 2D illustration of CVB4 Domain I secondary structure. Numbers indicate nucleotide positions. (C) From (23) by license: Creative Commons Attribution 4.0 International. An integrated model for enterovirus replication. Negative-strand synthesis is initiated by circularization of the positive-strand genome via a protein-protein bridge through the interaction of the ternary complex at the 5′-end (3CD and PCBP bound to the cloverleaf structure) and PABP bound to the 3′-poly(A)tail (I. + II.). CRE-mediated VPg-pUpU acts as primer of the reaction and the polymerase 3D synthesizes the new negative-strand (III.), resulting in a double-stranded intermediate (RF) (IV.). The positive-negative duplex RNA intermediate unwinds, so that the cloverleaf structure at the 5′-end of the positive-strand can form. 3CD and PCBP bind to the cloverleaf to form a ternary complex, which, in turn, will…

Figure 2. Schematic showing primer binding sites across an enteroviral genome. 5′UTR domains are indicated by roman numerals. Numbers on top of the representative genome indicate nucleotide position. Forward and reverse primers as well as probes (if applicable) are indicated across all 8 PCR methodologies used across enterovirus-related ME/CFS studies. Dark blue arrows indicate forward primers, dark green arrows indicated reverse primers, second round primers used in nested PCR approaches are indicated by light blue (forward) and light green (reverse) arrows. Red bars indicate probes and the one gray arrow indicates a primer used in the primary reverse transcription step.