HLA-A33 Is Associated With Susceptibility to Enterovirus 71 Infection

Chang, Luan‐Yin; Chang, I‐Shou; Chen, Wei-Jen; Huang, Yhu-Cherng; Chen, Guang-Wu; Shih, Shin‐Ru; Juang, Jyh‐Lyh; Shih, Hsiu‐Ming; Hsiung, Chao A.; Lin, Tzou–Yien; Huang, Lin-Min

doi:10.1542/peds.2007-3735

Cited by 72 publications

(49 citation statements)

References 37 publications

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“…73,74,85 One genetic study in Taiwan reported that HLA-A33 is associated with increased susceptibility to EV71 infection, although the role of MHC remains unknown. 86 The researchers noted that HLA-A33 is more frequent in Asian populations than in white populations, which might explain the high number of EV71 epidemics in Asia. They suggested also that HLA-A2, in a mechanism yet to be defi ned, could be linked to the risk of cardiopulmonary failure in patients with EV71.…”

Section: Host Susceptibilitymentioning

confidence: 99%

“…They suggested also that HLA-A2, in a mechanism yet to be defi ned, could be linked to the risk of cardiopulmonary failure in patients with EV71. 86 The CTLA4 gene is an important regulator of T-cell cytotoxicity, and it has a role in the regulation of an immune response. In a study of 78 children with EV71 infection in Taiwan, those with meningoencephalitis had a higher frequency of G/G genotype at position 49 of exon 1 in this gene, than those without meningoencephalitis and controls.…”

Section: Host Susceptibilitymentioning

confidence: 99%

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Virology, epidemiology, pathogenesis, and control of enterovirus 71

Solomon

Lewthwaite

Perera

et al. 2010

The Lancet Infectious Diseases

1,134

1,007

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First isolated in California, USA, in 1969, enterovirus 71 (EV71) is a major public health issue across the Asia-Pacifi c region and beyond. The virus, which is closely related to polioviruses, mostly aff ects children and causes hand, foot, and mouth disease with neurological and systemic complications. Specifi c receptors for this virus are found on white blood cells, cells in the respiratory and gastrointestinal tract, and dendritic cells. Being an RNA virus, EV71 lacks a proofreading mechanism and is evolving rapidly, with new outbreaks occurring across Asia in regular cycles, and virus gene subgroups seem to diff er in clinical epidemiological properties. The pathogenesis of the severe cardiopulmonary manifestations and the relative contributions of neurogenic pulmonary oedema, cardiac dysfunction, increased vascular permeability, and cytokine storm are controversial. Public health interventions to control outbreaks involve social distancing measures, but their eff ectiveness has not been fully assessed. Vaccines being developed include inactivated whole-virus, live attenuated, subviral particle, and DNA vaccines.

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Section: Host Susceptibilitymentioning

confidence: 99%

Section: Host Susceptibilitymentioning

confidence: 99%

Virology, epidemiology, pathogenesis, and control of enterovirus 71

Solomon

Lewthwaite

Perera

et al. 2010

The Lancet Infectious Diseases

1,134

1,007

View full text Add to dashboard Cite

show abstract

“…Severe and fatal EV71 infections are predominantly found in young children, with male patients outnumbering female patients (12,52). There has been a substantial increase in the frequency and severity of EV71 epidemics in recent years, particularly in the Asian Pacific region (5,13,58,65), prompting urgent, ongoing investigations of the virological and host factors contributing to the apparently increasing pathogenicity of the virus (5,11,58).…”

mentioning

confidence: 99%

The Association of Recombination Events in the Founding and Emergence of Subgenogroup Evolutionary Lineages of Human Enterovirus 71

Leitch

Cabrerizo

Cardosa

et al. 2012

J Virol

109

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Enterovirus 71 (EV71) is responsible for frequent large-scale outbreaks of hand, foot, and mouth disease worldwide and represent a major etiological agent of severe, sometimes fatal neurological disease. EV71 variants have been classified into three genogroups (GgA, GgB, and GgC), and the latter two are further subdivided into subgenogroups B1 to B5 and C1 to C5. To investigate the dual roles of recombination and evolution in the epidemiology and transmission of EV71 worldwide, we performed a largescale genetic analysis of isolates (n ‫؍‬ 308) collected from 19 countries worldwide over a 40-year period. A series of recombination events occurred over this period, which have been identified through incongruities in sequence grouping between the VP1 and 3Dpol regions. Eleven 3Dpol clades were identified, each specific to EV71 and associated with specific subgenogroups but interspersed phylogenetically with clades of coxsackievirus A16 and other EV species A serotypes. The likelihood of recombination increased with VP1 sequence divergence; mean half-lives for EV71 recombinant forms (RFs) of 6 and 9 years for GgB and GgC overlapped with those observed for the EV-B serotypes, echovirus 9 (E9), E30, and E11, respectively (1.3 to 9.8 years). Furthermore, within genogroups, sporadic recombination events occurred, such as the linkage of two B4 variants to RF-W instead of RF-A and of two C4 variants to RF-H. Intriguingly, recombination events occurred as a founding event of most subgenogroups immediately preceding their lineage expansion and global emergence. The possibility that recombination contributed to their subsequent spread through improved fitness requires further biological and immunological characterization.

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“…However, 80% of EV71-infected patients become positive for EV71-specific neutralizing Abs 1 d after the onset of illness, and the magnitude of Ab responses are not correlated with disease severity and outcome (19). In contrast, documented clues imply that cellular but not humoral immune responses are correlated with disease progression and clinical outcome (20,21).…”

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confidence: 99%

VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population

Tan

Sun

et al. 2013

The Journal of Immunology

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Enterovirus 71 (EV71)–associated hand-foot-mouth disease has become a major threat to public health in the Asia–Pacific region. Although T cell immunity is closely correlated with clinical outcomes of EV71 infection, little is known about T cell immunity baseline against EV71 and T cell immunogenecity of EV71 Ags in the population, which has restricted our understanding of immunoprotection mechanisms. In this study, we investigated the cellular immune responses against the four structural Ags of EV71 and determined the immunohierarchy of these Ags in healthy adults. A low frequency of EV71-responsive T cells was detected circulating in peripheral blood, and broad T cell immune responses could be identified in most of the subjects after in vitro expansion. We demonstrated that the VP2 Ag with broad distribution of immunogenic peptides dominates T cell responses against EV71 compared with VP1, VP3, and VP4. Furthermore, the responses were illuminated to be mainly single IFN-γ–secreting CD4+ T cell dependent, indicating the previous natural acute viral infection of the adult population. Conservancy analysis of the immunogenic peptides revealed that moderately variant peptides were in the majority in coxsackievirus A16 (CV-A16) whereas most of the peptides were highly variant in polioviruses. Less efficient cross-reactivity against CV-A16 might broadly exist among individuals, whereas influences derived from poliovirus vaccination would be limited. Our findings suggest that the significance of VP2 Ag should be addressed in the future EV71-responsive immunological investigations. And the findings concerning the less efficient cross-reactivity against CV-A16 and limited influences from poliovirus vaccination in EV71-contacted population would contribute to a better understanding of immunoprotection mechanisms against enteroviruses.

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HLA-A33 Is Associated With Susceptibility to Enterovirus 71 Infection

Abstract: The authors have indicated they have no financial relationships relevant to this article to disclose. What's Known on This SubjectEnterovirus 71 has caused large epidemics of disease, resulting in many fatalities and severe sequelae, in Taiwan and some other countries.

Cited by 72 publications

References 37 publications

Virology, epidemiology, pathogenesis, and control of enterovirus 71

Virology, epidemiology, pathogenesis, and control of enterovirus 71

The Association of Recombination Events in the Founding and Emergence of Subgenogroup Evolutionary Lineages of Human Enterovirus 71

VP2 Dominated CD4+ T Cell Responses against Enterovirus 71 and Cross-Reactivity against Coxsackievirus A16 and Polioviruses in a Healthy Population

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