An outbreak of epidemic keratoconjunctivitis caused by human adenovirus type 8 in primary school, southwest China

Epidemic keratoconjunctivitis (EKC) is a severe ocular disease and can lead to visual impairment. Human adenovirus type-37 (HAdV-D37) is one of the major causative agents of EKC and uses sialic acid (SA)-containing glycans as cellular receptors. Currently, there are no approved antivirals available for the treatment of EKC. Recently, we have reported that sulfated glycosaminoglycans (GAGs) bind to HAdV-D37 via the fiber knob (FK) domain of the viral fiber protein and function as decoy receptors. Based on this finding, we speculated that GAG-mimetics may act as artificial decoy receptors and inhibit HAdV-D37 infection. Repurposing of approved drugs to identify new antivirals has drawn great attention in recent years. Here, we report the antiviral effect of suramin, a WHO-approved drug and a widely known GAG-mimetic, against HAdV-D37. Commercially available suramin analogs also show antiviral effects against HAdV-D37. We demonstrate that suramin exerts its antiviral activity by inhibiting the attachment of HAdV-D37 to cells. We also reveal that the antiviral effect of suramin is HAdV species-specific. Collectively, in this proof of concept study, we demonstrate for the first time that virus binding to a decoy receptor constitutes a novel and an unexplored target for antiviral drug development.

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An Outbreak of Epidemic Keratoconjunctivitis Caused by Human Adenovirus Type 8 in Primary School, Southwest China

10.21203/rs.2.514/v4 ◽

2019 ◽

Author(s):

Duo Li ◽

Jie-Nan Zhou ◽

Hong Li ◽

Cun-Ying He ◽

Qing-Shan Dai ◽

...

Keyword(s):

Risk Factors ◽

Primary School ◽

Primary Schools ◽

Southwest China ◽

Close Contact ◽

Clinical Manifestations ◽

Epidemic Keratoconjunctivitis ◽

Blurred Vision ◽

Epidemiological Characteristics ◽

Acute Conjunctivitis

Abstract Background: Two outbreaks of epidemic keratoconjunctivitis (EKC) occurred successively with an interval of five days in two primary boarding schools in Weixi Lisu Autonomous County, Diqing, and Tibetan Autonomous Prefecture, Yunnan. The aims of this study were to determine the intensity and characteristics of the outbreaks, as well as the clinical manifestations in the patients, the risk factors for infection and the pathogen responsible for the two outbreaks. Methods: An outbreak investigation was conducted in two primary schools, and a case-control study including patients from the Weixi County Ethnic Primary School was performed. Relevant specimens were collected according to the case definition, and next-generation sequencing was employed to identify the pathogen. An epidemiological investigation method was used to analyse the related epidemiological characteristics, such as risk factors. The phylogenetic tree was constructed by MEGA 7.0. Results: A total of 331 acute conjunctivitis cases, including probable cases of EKC, were reported in the two schools, and the attack rates were 30.59% (171/559, 95%CI: 26.76-34.42) and 20.41% (160/784, 95%CI: 17.58-23.24), respectively. Cases occurred in all grades and classes in both schools, and only one staff member in each school presented illness. The epidemics lasted for 54 days and 45 days, respectively. The patients had typical manifestations of EKC, such as acute onset, follicular hyperplasia, pseudomembrane formation, preauricular lymphadenopathy, corneal involvement and blurred vision, and a relatively long disease course (average 9.40 days, longest 23 days and shortest 7 days). The risk factor for infection was close contact with a patient or personal items contaminated by a patient. The pathogen responsible for the outbreaks was HAdV-8. The virus was highly similar to the 2016 HAdV-8 strain from Tibet, China. Conclusions: This study strongly suggests that HAdV-8 could lead to serious consequences. This is the second report of a HAdV-8-associated EKC outbreak in mainland China. Tibetan HAdV-8 might be circulating in southwest China; therefore, it is necessary to monitor the pathogens causing acute conjunctivitis in this area.

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Notes from the Field: Epidemic Keratoconjunctivitis Outbreak Associated with Human Adenovirus Type 8 — U.S. Virgin Islands, June–November 2016

MMWR Morbidity and Mortality Weekly Report ◽

10.15585/mmwr.mm6630a3 ◽

2017 ◽

Vol 66 (30) ◽

pp. 811-812 ◽

Cited By ~ 4

Author(s):

Marie E. Killerby, ◽

Matthew J. Stuckey, ◽

Irene Guendel, ◽

Senthilkumar Sakthivel, ◽

Xiaoyan Lu, ◽

...

Keyword(s):

Human Adenovirus ◽

Adenovirus Type ◽

Virgin Islands ◽

Epidemic Keratoconjunctivitis

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Human adenovirus type 8 epidemic keratoconjunctivitis with large corneal epithelial full-layer detachment: an endemic outbreak with uncommon manifestations

Clinical Ophthalmology ◽

10.2147/opth.s79697 ◽

2015 ◽

pp. 953 ◽

Cited By ~ 6

Author(s):

Yueh-Chang Lee ◽

Nancy Chen ◽

I-Tsong Huang ◽

Hui-Hua Yang ◽

Chin-Te Huang ◽

...

Keyword(s):

Human Adenovirus ◽

Adenovirus Type ◽

Epidemic Keratoconjunctivitis ◽

Corneal Epithelial

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Five Cases of Epidemic Keratoconjunctivitis Due to Human Adenovirus Type 85 in Fukushima, Japan

Japanese Journal of Infectious Diseases ◽

10.7883/yoken.jjid.2020.034 ◽

2020 ◽

Vol 73 (4) ◽

pp. 316-319

Author(s):

Hisatoshi Kaneko ◽

Nozomu Hanaoka ◽

Masami Konagaya ◽

Masaaki Kobayashi ◽

Hisashi Nakagawa ◽

...

Keyword(s):

Human Adenovirus ◽

Adenovirus Type ◽

Epidemic Keratoconjunctivitis

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Outbreaks of epidemic keratoconjunctivitis caused by human adenovirus type 8 in the Tibet Autonomous Region of China in 2016

PLoS ONE ◽

10.1371/journal.pone.0185048 ◽

2017 ◽

Vol 12 (9) ◽

pp. e0185048 ◽

Cited By ~ 10

Author(s):

Zhenqiang Lei ◽

Zhen Zhu ◽

Bai ma ci wang ◽

Hong mei ◽

Hong Li ◽

...

Keyword(s):

Human Adenovirus ◽

Adenovirus Type ◽

Epidemic Keratoconjunctivitis ◽

Autonomous Region ◽

Tibet Autonomous Region ◽

The Tibet Autonomous Region

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Analysis of the complete genome sequence of epidemic keratoconjunctivitis-related human adenovirus type 8, 19, 37 and a novel serotype

Journal of General Virology ◽

10.1099/vir.0.009225-0 ◽

2009 ◽

Vol 90 (6) ◽

pp. 1471-1476 ◽

Cited By ~ 37

Author(s):

Hisatoshi Kaneko ◽

Tomohiro Iida ◽

Hiroaki Ishiko ◽

Takeshi Ohguchi ◽

Toshihide Ariga ◽

...

Keyword(s):

Genome Sequence ◽

Complete Genome Sequence ◽

Complete Genome ◽

Human Adenovirus ◽

Adenovirus Type ◽

Clinical Strain ◽

Epidemic Keratoconjunctivitis ◽

Hypervariable Regions ◽

Distinct Cluster ◽

Loop 2

We determined the complete genome sequence of epidemic keratoconjunctivitis (EKC)-related human adenoviruses (HAdVs). We analysed a total of 12 HAdV strains; three prototype strains and two HAdV-8, three HAdV-19 and three HAdV-37 clinical isolates from EKC patients in Japan, and one novel serotype of HAdV. Genome organization of these serotypes was identical to those of the recently determined HAdV-19 and HAdV-37. The identities of the whole genome were over 99 % among strains from the same serotype, except for HAdV-19p, which is not associated with conjunctivitis, resulting in the formation of a distinct cluster in the phylogenetic analysis. The penton, loop 1 and loop 2 of hexon, early region 3 (E3) and fiber were hypervariable regions between serotypes. Results suggest that the HAdV-19 clinical strain is a recombinant of HAdV-19p-like and HAdV-37-like strains, and that the acquisition of the penton, E3 or fiber may be related to ocular tropism.

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Recombination analysis of intermediate human adenovirus type 53 in Japan by complete genome sequence

Journal of General Virology ◽

10.1099/vir.0.030361-0 ◽

2011 ◽

Vol 92 (6) ◽

pp. 1251-1259 ◽

Cited By ~ 30

Author(s):

Hisatoshi Kaneko ◽

Koki Aoki ◽

Susumu Ishida ◽

Shigeaki Ohno ◽

Nobuyoshi Kitaichi ◽

...

Keyword(s):

Complete Genome ◽

Phylogenetic Analyses ◽

Human Adenovirus ◽

Adenovirus Type ◽

Penton Base ◽

Recombination Detection Program ◽

Genome Sequences ◽

Epidemic Keratoconjunctivitis ◽

Detection Program ◽

Recombination Breakpoints

Human adenovirus type 53 (HAdV-53) has commonly been detected in samples from epidemic keratoconjunctivitis (EKC) patients in Japan since 1996. HAdV-53 is an intermediate virus, containing hexon-chimeric, penton base and fiber structures similar to HAdV-22 and -37, HAdV-37 and HAdV-8, respectively. HAdV-53-like intermediate strains were first isolated from EKC samples in Japan in the 1980s. Here, the complete genome sequences of three such HAdV-53-like intermediate strains (870006C, 880249C and 890357C) and four HAdV-53 strains were determined, and their relationships were analysed. The seven HAdV strains were classified into three groups, 870006C/880249C, 890357C and the four HAdV-53 strains, on the basis of phylogenetic analyses of the partial and complete genome sequences. HAdV strains within the same group showed the highest nucleotide identities (99.87–100.00 %). Like HAdV-53, the hexon loop 1 and 2 regions of 870006C, 880249C and 890357C showed the highest identity with HAdV-22. However, these strains did not show a hexon-chimeric structure similar to HAdV-22 and -37, or a penton base similar to HAdV-37. The fiber genes of 870006C and 880249C were identical to that of HAdV-37, but not HAdV-8. Thus, the three intermediate HAdVs isolated in the 1980s were similar to each other but not to HAdV-53. The recombination breakpoints were inferred by the Recombination Detection Program (rdp) using whole-genome sequences of these seven HAdV and of 12 HAdV-D strains from GenBank. HAdV-53 may have evolved from intermediate HAdVs circulating in the 1980s, and from HAdV-8, -22 and -37, by recombination of sections cut at the putative breakpoints.

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