The 1998 Enterovirus 71 Outbreak in Taiwan: Pathogenesis and Management

Lin, Tzou Yien; Chang, Luan‐Yin; Hsia, Shao Hsuan; Huang, Yhu Chering; Chiu, Cheng Hsun; Hsueh, Chuen; Shih, Shin Ru; Liu, Ching Chuan; Wu, Mei‐Hwan

doi:10.1086/338819

Cited by 177 publications

(162 citation statements)

References 15 publications

Supporting

Mentioning

156

Contrasting

Order By: Relevance

“…The brain stem is most likely the major target of EV71 infection (2,8). However, neither the host cell receptor nor the neurotransmission route of EV71 is fully defined.…”

mentioning

confidence: 99%

Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

Chen¹,

Yao²,

Lin³

et al. 2007

J Virol

Self Cite

154

126

View full text Add to dashboard Cite

Enterovirus 71 (EV71), a single-positive-stranded RNA virus that belongs to the Enterovirus genus of the Picornaviridae family, is a highly neurotropic virus and has been regarded as the most important neurotropic EV after the eradication of the poliovirus (11). The brain stem is most likely the major target of EV71 infection (2, 8). However, neither the host cell receptor nor the neurotransmission route of EV71 is fully defined.As for poliovirus (PV), two possible routes by which the virus reaches the central nervous system (CNS) have been suggested: the virus either enters the CNS from the blood across the blood-brain barrier (BBB) or is transmitted to the CNS through peripheral nerves via retrograde axonal transport (1,3,14,23). Expression of certain gene segments would be responsible for determining the capacity of PV to spread to the CNS through bloodstream or neuronal pathways (18).In a cynomologus monkey model (12, 13), EV71 showed a wider-spread distribution pattern in the CNS than PV following both intracranial (i.c.) and intravenous inoculations, and monkeys exhibited extrapyramidal signs, including tremor and ataxia. However, after intraspinal inoculation, monkeys developed flaccid paralysis, a pyramidal sign suggesting direct virus invasion in the inoculation site. EV infection and persistence have been implicated in the pathogenesis of certain chronic muscle diseases (17). Furthermore, PV replicated in muscle cells that maintained constant viremia and spread to CNS from peripheral nerves (23). We previously showed that EV71 propagated more effectively in RD (human rhabdomyosarcoma) cells than in SK-N-SH (neuroblastoma) cells and Caco-2 (colorectal adenocarcinoma) cells. Furthermore, after oral (p.o.) inoculation of a mouse-adapted EV71 strain, EV71/MP4, 7-day-old ICR mice developed paralysis, with a mortality rate of 80%. Virus was first seen in the intestine. The virus then spread to muscle and CNS. A vast amount of virus was detected in the CNS and muscle, which led to neuronal loss and rhabdomyolysis of the mice with severe paralysis (21). In this study, we demonstrated that EV71 possesses strong neurotropism and that retrograde axonal transport in neuron cells might represent the major transmission route of EV71 in mice. MATERIALS AND METHODSCells and virus. RD cells (American Type Culture Collection, Manassas, VA) were maintained in Dulbecco's modified Eagle's medium containing 10% fetal bovine serum plus 2 mM L-glutamine, 100 IU penicillin, and 100 g of streptomycin per ml. EV71/MP4 strain, a mouse-adapted strain derived from parental virus EV71/Tainan/4643/98 (GenBank accession number AF304458) (22), was grown in RD cells. Working stocks contained 2 ϫ 10 7 PFU/ml. Experimental infection. Specific-pathogen-free, 7-day-old ICR mice

show abstract

“…The brain stem is most likely the major target of EV71 infection (2,8). However, neither the host cell receptor nor the neurotransmission route of EV71 is fully defined.…”

mentioning

confidence: 99%

Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

Chen¹,

Yao²,

Lin³

et al. 2007

J Virol

Self Cite

154

126

View full text Add to dashboard Cite

show abstract

“…Although EV71 was recovered from the mycocardium, there was only mild degeneration of the mycocardium. Neurogenic shock as a result of brain stem encephalitis has been proposed as the cause of pulmonary and cardiac complications (13,16). It has also been postulated that overwhelming virus replication combined with damage in tissues with the induction of toxic inflammatory cytokines is one possible pathogenesis (14,15,27).…”

mentioning

confidence: 99%

A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection

Wang

Chou²,

Lei³

et al. 2004

J Virol

Self Cite

237

241

View full text Add to dashboard Cite

A mouse-adapted enterovirus 71 (EV71) strain with increased virulence in mice, MP4, was generated after four serial passages of the parental EV71 strain 4643 in mice. Strain MP4 exhibited a larger plaque size, grew more rapidly, and was more cytotoxic in vitro than strain 4643. Although strains 4643 and MP4 both induced apoptosis of SK-N-SH human neuroblastoma cells, MP4 was more virulent than 4643 in 1-day-old mice (50% lethal doses, 10 2 and 10 4 PFU/mouse, respectively). Strain MP4 (5 ؋ 10 6 PFU/mouse), but not 4643, could orally infect 7-day-old mice, resulting in rear-limb paralysis followed by death 5 to 9 days after inoculation with the virus. Histopathologically, neuronal loss and apoptosis were evident in the spinal cords as well as the brain stems of the infected mice. The limb muscles displayed massive necrosis. There was early and transient virus replication in the intestines, whereas the spinal cord, brain, and muscle became the sites of viral replication during the late phase of the infection. Virus transmission occurred among infected and noninfected cagemates, as demonstrated by the occurrence of seroconversion and the presence of viable viruses in the stool samples of the latter. Protection against EV71 challenge was demonstrated following administration of hyperimmune serum 1 day after inoculation with the virus. Nucleotide sequence analysis of the genome of EV71 strain MP4 revealed four nucleotide changes on the 5 untranslated region, three on the VP2 region, and eight on the 2C region, resulting in one and four amino acid substitutions in the VP2 and 2C proteins, respectively.Enterovirus 71 (EV71), a neurotropic virus with undefined pathogenesis, has caused significant morbidity and mortality worldwide and especially in the Asia-Pacific region since it was first described in 1969 in the United States (1, 2). EV71 infections are generally mild, such as hand-foot-and-mouth disease (HFMD) and herpangina, but occasionally lead to severe diseases such as aseptic meningitis, poliomyelitis-like paralysis, and possibly fatal encephalitis in neonates. The outbreak of EV71 in Taiwan in 1998 killed 78 children, and since then EV71 infection has become endemic in Taiwan (8, 16). Brain stem encephalitis associated with pulmonary edema and cardiac insufficiency were the primary manifestations in patients with neurologic involvement (10, 16, 28). The predominant pathological findings were in the thalamus, pons, midbrain, medulla oblongata, and spinal cord, with intense neutrophil and mononuclear cell infiltrates. There was severe congestion with focal hemorrhage and edema in the lungs (21). Although EV71 was recovered from the mycocardium, there was only mild degeneration of the mycocardium. Neurogenic shock as a result of brain stem encephalitis has been proposed as the cause of pulmonary and cardiac complications (13,16). It has also been postulated that overwhelming virus replication combined with damage in tissues with the induction of toxic inflammatory cytokines is one possible pathogenesis (14,15,27)...

show abstract

“…(I) those with CNS involvement (II) those with ANS dysregulation (profuse sweating and respiratory abnormalities, persistent tachycardia and hypertension) and, (III) later, those with frank cardiopulmonary failure, including pulmonary edema or hemorrhage [23]. CSF study support the assessment with the finding of leukocytosis, thrombocytosis and hyperglycemia.…”

Section: Managementmentioning

confidence: 88%

Hand, Foot and Mouth Disease: A case report

Sah¹

2017

Janaki Med. Coll. J. Med. Sci.

View full text Add to dashboard Cite

Hand, foot & mouth disease (HFMD) is a common emerging infectious disease caused by intestinal viruses of the picornaviridae family. A strain of Coxsackie virus (A16, A5, A6) is chiefly instrumental for producing this condition however more severe form is caused by Enterovirus-71. Though HFMD is a mild disease and can often be effectively and competently managed in an outpatient setting, recent outbreaks in the western pacific region with fatal form of disease have attracted the concern about the clinical assessment and appropriate management of HFMD. Early detection and good clinical judgments not only can prevent the fatal progression but also can reduce overall morbidity and mortality regarding HFMD. I am presenting a case report of the afore mentioned disease and the subsequent early clinical manifestation of the fatal form of HFMD to enlighten on the nature of the disease so that early diagnosis and management of the condition can be carried out to halt the disease progression and prevention for the betterment of children especially under five years.

show abstract

The 1998 Enterovirus 71 Outbreak in Taiwan: Pathogenesis and Management

Cited by 177 publications

References 15 publications

Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

Retrograde Axonal Transport: a Major Transmission Route of Enterovirus 71 in Mice

A Mouse-Adapted Enterovirus 71 Strain Causes Neurological Disease in Mice after Oral Infection

Hand, Foot and Mouth Disease: A case report

Contact Info

Product

Resources

About