Human adenovirus type identification

Dear editor

The published paper in your journal entitling “Human adenovirus type 8 epidemic keratoconjunctivitis with large corneal epithelial full-layer detachment: an endemic outbreak with uncommon manifestations” has come into our attention.¹ The article provides interesting clinical presentation of corneal epithelial layer detachment among 25% (4 out of 16 human adenovirus [HAdV]-positive cases) of patients diagnosed with epidemic keratoconjunctivitis (EKC).

However, we have some opinions about the article that are stated below:

First, we have noticed that the authors have used the combination of hexon gene sequence and BLASTN for the typing of HAdV. Due to the appearance of many recombinant types of HAdVs, especially the EKC causing ones, for the last few years, many isolates were wrongly diagnosed as HAdV-8 by serological method. For example, type HAdV-54 was diagnosed as HAdV-8 due to cross reaction in neutralization test.² Even this was described as genome type HAdV-8I due to its misidentification as HAdV-8.^3,4 Nowadays, HAdV-54 has become the major agent of EKC in Japan, although a few HAdV-8 is still being isolated in some places.^5–9 Another EKC causing recombinant type HAdV-53 carries the fiber gene of HAdV-8, penton of HAdV-37, and the hexon of HAdV-22.⁹

Therefore, current recommended type identification method of HAdV is sequencing of the penton (P)-hexon (H)-fiber (F) genes (molecular typing) or whole genome sequence.¹⁰

Second, the authors used the term HAdV-8 genotype on the basis of HAdV-8 hexon sequence followed by BLASTN. Now a days, PCR amplification and sequencing of variable regions within the hexon, penton base, and fiber genes is designated as molecular typing method.

The term genotype is used for the recognition of a new type by full genome sequence. A genotype number is assigned where sequence data reveal that either i) the virus isolate encodes novel hexon (loops 1 and 2), penton base (hypervariable region), and fiber (knob) sequences, or ii) is a recombinant with one or two of these regions derived from previously designated genotypes, or iii) is a recombinant that has a unique combination of these three regions derived from previously recognized genotypes.¹⁰

Third, in the discussion, the authors described HAdV-8C–H genome types as genotypes. Traditionally, genome types of HAdV are designated by the restriction endonuclease cleavage pattern analysis of viral DNA.¹¹

We hope the authors will perform the currently recommended methods to confirm the identity of their EKC causing HAdVs.

Disclosure

The authors report no conflicts of interest in this work.

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References

1.		Lee YC, Chen N, Huang IT, et al. Human adenovirus type 8 epidemic keratoconjunctivitis with large corneal epithelial full-layer detachment: an endemic outbreak with uncommon manifestations. Clin Ophthalmol. 2015;9:953–957.
2.		Kaneko H, Suzutani T, Aoki K, et al. Epidemiological and virological features of epidemic keratoconjunctivitis due to new human adenovirus type 54 in Japan. Br J Ophthalmol. 2011;95(1):32–36. doi:10.1136/bjo.2009.178772.
3.		Adhikary AK, Numaga J, Kaburaki T, et al. Genetic characterisation of adenovirus type 8 isolated in Hiroshima city over a 15 year period. J Clin Pathol. 2003;56(2):120–125.
4.		Adhikary AK, Ushijima H, Fujimoto T. Human adenovirus type 8 genome typing. J Med Microbiol. 2012;61(Pt 11):1491–1503. doi:10.1099/jmm.0.044172-10.
5.		Ishiko H, Shimada Y, Konno T, et al. Novel human adenovirus causing nosocomial epidemic keratoconjunctivitis. J Clin Microbiol. 2008;46(6):2002–2008. doi:10.1128/JCM.01835-07.
6.		Ishiko H, Aoki K. Spread of epidemic keratoconjunctivitis due to a novel serotype of human adenovirus in Japan. J Clin Microbiol. 2009;47(8):2678–2679. doi:10.1128/JCM.r00313-109.
7.		Akiyoshi K, Suga T, Fukui K, Taniguchi K, Okabe N, Fujimoto T. Outbreak of epidemic keratoconjunctivitis caused by adenovirus type 54 in a nursery school in Kobe City, Japan in 2008. Jpn J Infect Dis. 2011;64(4):353–355.
8.		Fujimoto T, Matsushima Y, Shimizu H, et al. A molecular epidemiologic study of human adenovirus type 8 isolates causing epidemic keratoconjunctivitis in Kawasaki City, Japan in 2011. Jpn J Infect Dis. 2012;65(3):260–263.
9.		Nakamura M, Hirano E, Kowada K, et al. Surveillance of adenovirus D in patients with epidemic keratoconjunctivitis from Fukui Prefecture, Japan, 1995–2010. J Med Virol. 2012;84(1):81–86. doi:10.1002/jmv.22252.
10.		Seto D, Chodosh J, Brister JR, Jones MS; Members of the Adenovirus Research Community. Using the whole-genome sequence to characterize and name human adenoviruses. J Virol. 2011;85(11):5701–5702. doi:10.1128/JVI.00354-11.
11.		Adrian T, Wadell G, Hierholzer JC, Wigand R. DNA restriction analysis of adenovirus prototypes 1 to 41. Arch Virol. 1986;91(3–4):277–290.