Chapter 16 : Enteroviruses and Human Neuromuscular Diseases

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Coxsackieviruses, echoviruses, and polioviruses have been implicated in the pathogenesis of human neuromuscular diseases because o f their association with certain acute and chronic acquired myopathies and paralytic motor neuron syndromes. The advent of new molecular techniques has added to both the capability of establishing and the controversy surrounding the role of enteroviruses in various acquired inflammatory muscle diseases and motor neuron syndromes such as polymyositis (PM), dermatomyositis (DM), chronic fatigue syndrome (CFS), postpolio syndrome (PPS), and amyotrophic lateral sclerosis (ALS), each of which is discussed in this chapter. The author has studied muscle biopsy specimens from 39 patients (16 with PM, 12 with DM, and 11 with inclusion body myositis) who fulfilled the strict diagnostic clinicopathologic criteria of active inflammatory myopathy. Two recent studies using in situ hybridization, PCR, and sequence analysis of the amplified product have shown the presence of an enterovirus that differs from the typical strains in the 5' non coding region, suggesting a virus defective or mutated in that region. Biologic plausibility coupled with preliminary laboratory data has focused much attention on the enteroviruses as causative agents in numerous acute and chronic human muscle diseases.

Citation: Dalakas M. 1995. Enteroviruses and Human Neuromuscular Diseases, p 387-398. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch16
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Polyacrylamide gel electrophoreses of enterovirus PCR performed on extracted RNA from muscle biopsy samples of patients with inflammatory myopathies and other neuromuscular diseases; also included are positive tissue culture and negative water controls subjected to the same amplification techniques. Lanes 1 through 4 (panel A) and 1 and 2 (panel B) are from patients with PM; lanes 5 through 8 (panel A) and 3 and 4 (panel B) are from patients with DM; lanes 5 through 7 (panel B) are from patients with inclusion body myositis; and lanes 9 and 10 (panel A) and 8 through 10 (panel B) are from patients with other neuromuscular diseases including PPS. Lane P, amplified RNA from poliovirus-infected cell cultures; lane C, amplified RNA from coxsackievirus-infected cultures; lane W, amplification products obtained from water alone; lane MW, molecular weight markers (in thousands). Specific amplification of the expected 154-bp fragment of enteroviral RNA is shown by arrows and was observed in virus-infected cells only; arrowheads indicate lower-molecular-weight bands that are nonspecific products. ( )

Citation: Dalakas M. 1995. Enteroviruses and Human Neuromuscular Diseases, p 387-398. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch16
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Image of FIGURE 2

Slot blot hybridization of PCR products hybridized with a 23-mer 32P-labeled oligonucleotide probe. Slots 1 through 6, amplified product from patients with PM; slots 7 through 12, product from patients with DM; slots 13 through 17, product from patients with inclusion body myositis; slots 18 through 23, product from other disease controls including patients with PPS. P1, P2, and P3, amplified products from cell cultures infected with polioviruses 1, 2, and 3, respectively; W, amplified products of water alone; P(s), products from the supernatant of poliovirus-infected cells. Specific hybridization is noted only in virus-infected culture controls [P1, P2, P3, P(s)] but not in muscle biopsy specimens ( ).

Citation: Dalakas M. 1995. Enteroviruses and Human Neuromuscular Diseases, p 387-398. In Rotbart H (ed), Human Enterovirus Infections. ASM Press, Washington, DC. doi: 10.1128/9781555818326.ch16
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