Skip to main content
Log in

Genetic variability of human adenovirus type 8 causing epidemic and sporadic cases of keratoconjunctivitis

  • Original Article
  • Published:
Archives of Virology Aims and scope Submit manuscript

Abstract

Human adenovirus type 8 (HAdV-8) is a main aetiological agent of keratoconjunctivitis. It has been reported from both epidemic and sporadic cases. The aim of our study was to investigate the genetic characteristics and chronological pattern of HAdV-8 strains that have been circulating in Tunisia over a 14-year period. Fourteen HAdV-8 isolates from a keratoconjunctivitis outbreak that occurred in 2000 and from sporadic cases between 2001 and 2013 were studied. Nucleotide sequences from the hexon, fiber and penton base genes were determined, including hypervariable regions of the hexon (loops 1 and 2), the fiber (knob) and the penton base (HVR 1 and RGD loops). The sequences were compared to each other and to those of HAdV-8 strains. The Tunisian sequences were unique when compared to the previously published sequences. Also, despite a relatively low degree of genetic variation in the three genomic regions, phylogenetic analysis and alignment of amino acid sequences showed that the sequence from the year 2000 and two other sequences from the year 2013 were similar to each other and differed from the isolates that circulated in the intervening year by two main amino acid changes in the loop 1 hexon gene and the knob-fiber gene. Our results confirm the genetic variability of HAdV-8 and document the chronological changes of circulating genetic variants.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. http://www.ictvonline.org/virustaxonomy.asp. Accessed 14-01-2016

  2. Robinson CM, Singh G, Henquell C, Walsh MP, Peigue-Lafeuille H, Seto D, Jones MS, Dyer DW, Chodosh J (2011) Computational analysis and identification of an emergent human adenovirus pathogen implicated in a respiratory fatality. Virology 409:141–147. doi:10.1016/j.virol.2010.10.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Singh G, Robinson CM, Dehghan S, Jones MS, Dyer DW, Seto D, Chodosh J (2013) Homologous recombination in E3 genes of human adenovirus species D. J Virol 87:12481–12488. doi:10.1128/JVI.01927-13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Darougar S, Walpita P, Thaker U, Viswalingam N, Gardner L, McSwiggan DA (1983) Adenovirus serotypes isolated from ocular infections in London. Br J Ophthalmol 67:111–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. González-López JJ, Morcillo-Laiz R, Muñoz-Negrete FJ (2013) Adenoviral keratocon-junctivitis: an update. Arch Soc Esp Oftalmol 88:108–115. doi:10.1016/j.oftal.2012.07.007

    Article  PubMed  Google Scholar 

  6. Jhanji V, Chan TC, Li EY, Agarwal K, Vajpayee RB (2015) Adenoviral keratoconjunctivitis. Surv Ophthalmol 60:435–443. doi:10.1016/j.survophthal.2015.04.001

    Article  PubMed  Google Scholar 

  7. Aoki K, Tagawa Y (2002) A twenty-one year surveillance of adenoviral conjunctivitis in Sapporo, Japan. Int Ophthalmol Clin 42:49–54

    Article  PubMed  Google Scholar 

  8. Nakamura M, Hirano E, Kowada K, Ishiguro F, Yamagishi Z, Adhikary AK, Hanaoka N, Okabe N, Taniguchi K, Fujimoto T (2012) Surveillance of adenovirus D in patients with epidemic keratoconjunctivitis from Fukui Prefecture, Japan, 1995–2010. J Med Virol 84:81–86. doi:10.1002/jmv.22252

    Article  PubMed  Google Scholar 

  9. Hiroi S, Morikawa S, Takahashi K, Komano J, Kase T (2013) Molecular epidemiology of human adenoviruses D associated with epidemic keratoconjunctivitis in Osaka, Japan, 2001–2010. Jpn J Infect Dis 66:436–438

    Article  PubMed  Google Scholar 

  10. Jawetz E, Kimura SJ, Hanna L, Coleman VR, Thygeson P, Nicholas A (1955) Studies on the etiology of epidemic keratoconjunctivitis. Am J Ophthalmol 40:200–209

    Article  CAS  PubMed  Google Scholar 

  11. Russell WC (2009) Adenoviruses: update on structure and function. J Gen Virol 90:1–20. doi:10.1099/vir.0.003087-0

    Article  CAS  PubMed  Google Scholar 

  12. Madisch I, Harste G, Pommer H, Heim A (2005) Phylogenetic analysis of the main neutralization and hemagglutination determinants of all human adenovirus prototypes as a basis for molecular classification and taxonomy. J Virol 79:15265–15276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Adhikary AK, Banik U (2014) Human adenovirus type 8: the major agent of epidemic keratoconjunctivitis (EKC). J Clin Virol 61:477–486. doi:10.1016/j.jcv.2014.10.015

    Article  CAS  PubMed  Google Scholar 

  14. Crawford-Miksza L, Schnurr DP (1996) Analysis of 15 adenovirus hexon proteins reveals the location and structure of seven hypervariable regions containing serotype-specific residues. J Virol 70:1836–1844

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Arnberg N, Kidd AH, Edlund K, Olfat F, Wadell G (2000) Initial interactions of subgenus D adenoviruses with A549 cellular receptors: sialic acid versus αv integrins. J Virol 74:7691–7693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Burmeister WP, Guilligay D, Cusack S, Wadell G, Arnberg N (2004) Crystal structure of species D adenovirus fiber knobs and their sialic acid binding sites. J Virol 78:7727–7736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Mei YF, Wadell G (1996) Epitopes and hemagglutination binding domain on sub-genus B: 2 adenovirus fibers. J Virol 70:3688–3697

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Swenson PD, Wadell G, Allard A et al (2003) Adenoviruses. In: Murray PR, Baron EJ, Pfaller MA, Jorgensen JH, Yolken RH (eds) Manual of clinical microbiology, 8th edn, vol 2. Washington, DC, pp 1404–1417

  19. Madisch I, Hofmayer S, Moritz C, Grintzalis A, Hainmueller J, Pring-Akerblom P, Heim A (2007) Phylogenetic analysis and structural predictions of human adenovirus penton proteins as a basis for tissue-specific adenovirus vector design. J Virol 81:8270–8281

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Adhikary AK, Banik U, Okabe N, Fujimoto T (2011) Molecular characterization of human adenovirus 8 (HAdV-8) including a novel genome type in Japan. Jpn J Infect Dis 64:493–498

    CAS  PubMed  Google Scholar 

  21. Mitsui Y, Hanna L, Hanabusa J, Minoda R, Ogata S, Kurihara H, Okamura R, Miura M (1959) Association of adenovirus type 8 with epidemic keratoconjunctivitis. AMA Arch Ophthalmol 61:891–898

    Article  CAS  PubMed  Google Scholar 

  22. Jernigan JA, Lowry BS, Hayden FG, Kyger SA, Conway BP, Gröschel DH, Farr BM (1993) Adenovirus type 8 epidemic keratoconjunctivitis in an eye clinic: risk factors and control. J Infect Dis 167:1307–1313

    Article  CAS  PubMed  Google Scholar 

  23. Centers for Disease Control and Prevention (CDC) (2013) Adenovirus-associated epidemic keratoconjunctivitis outbreaks—four states, 2008–2010. MMWR Morb Mortal Wkly Rep 62:637–641

    Google Scholar 

  24. Ersoy Y, Otlu B, Türkçüoğlu P, Yetkin F, Aker S, Kuzucu C (2012) Outbreak of adenovirus serotype 8 conjunctivitis in preterm infants in a neonatal intensive care unit. J Hosp Infect 80:144–149. doi:10.1016/j.jhin.2011.11.007

    Article  CAS  PubMed  Google Scholar 

  25. Fujii S, Nakazono N, Ishii K, Lin CC, Sheu MM, Chen CW, Fujinaga K (1984) Molecular epidemiology of adenovirus type 8 (Ad 8) in Taiwan: four subtypes recovered during the period of 1980–1981 from patients with epidemic keratoconjunctivitis. Jpn J Med Sci Biol 37:161–169

    Article  CAS  PubMed  Google Scholar 

  26. Adhikary AK, Numaga J, Kaburaki T, Kawashima H, Araie M, Ikeda Y, Ogino T, Suzuki E, Ushijima H, Mukoyama A, Matsuno S, Inada T, Okabe N (2003) Genetic characterisation of adenovirus type 8 isolated in Hiroshima city over a 15 year period. J Clin Pathol 56:120–125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Chang C, Sheu M, Chern C, Lin K, Huang W, Chen C (2001) Epidemic keratoconjunctivitis caused by a new genotype of adenovirus type 8 (Ad8)—a chronological review of Ad8 in Southern Taiwan. Jpn J Ophthalmol 45:160–166

    Article  CAS  PubMed  Google Scholar 

  28. Gordon YJ, Gordon RY, Romanowski E, Araullo-Cruz TP (1993) Prolonged recovery of desiccated adenoviral serotypes 5, 8, and 19 from plastic and metal surfaces in vitro. Ophthalmology 100:1835–1839

    Article  CAS  PubMed  Google Scholar 

  29. Rezig D, Bahri O, Ben Ayed N, Ben Yahia A, Sadraoui A, Ayed S, Triki H (2006) Identification of adenoviruses serotypes implicated in haemorrhagic conjunctivitis in Tunisia. Pathol Biol (Paris) 54:561–565

    Article  CAS  Google Scholar 

  30. Saitoh-Inagawa W, Oshima A, Aoki K, Itoh N, Isobe K, Uchio E, Ohno S, Nakajima H, Hata K, Ishiko H (1996) Rapid diagnosis of adenoviral conjunctivitis by PCR and restriction fragment length polymorphism analysis. J Clin Microbiol 34:2113–2116

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Shimada Y, Ariga T, Tagawa Y, Aoki K, Ohno S, Ishiko H (2004) Molecular diagnosis of human adenoviruses d and e by a phylogeny-based classification method using a partial hexon sequence. J Clin Microbiol 42:1577–1584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Ariga T, Shimada Y, Shiratori K, Ohgami K, Yamazaki S, Tagawa Y, Kikuchi M, Miyakita Y, Fujita K, Ishiko H, Aoki K, Ohno S (2005) Five new genome types of adenovirus type 37 caused epidemic keratoconjunctivitis in Sapporo, Japan, for more than 10 years. J Clin Microbiol 43:726–732

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ishii K, Nakazono N, Fujinaga K et al (1987) Comparative studies on aetiology and epidemiology of viral conjunctivitis in three countries of East Asia-Japan, Taiwan and South Korea. Int J Epidemiol 16:98–103

    Article  CAS  PubMed  Google Scholar 

  34. Vainio K, Borch E, Bruu AL (2001) No sequence variation in part of the hexon and the fibre genes of adenovirus 8 isolated from patients with conjunctivitis or epidemic keratoconjunctivitis (EKC) in Norway during 1989 to 1996. J Clin Pathol 54:558–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Berk AJ (2013) Adenoviridae. In: Knipe DM, Howley PM, Cohen JIJ, Griffin GE, Lamb RA, Martin MA et al (eds) Fields virology, 6th edn. Lippincott, Williams & Wilkins, Philadelphia, pp 1704–1731

    Google Scholar 

  36. Zhang Y, Bergelson JM (2005) Adenovirus receptors. J Virol 79:12125–12131

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Adhikary AK, Inada T, Banik U, Mukouyama A, Ikeda Y, Noda M, Ogino T, Suzuki E, Kaburaki T, Numaga J, Okabe N (2004) Serological and genetic characterization of a unique strain of adenovirus involved in outbreak of epidemic keratoconjunctivitis (EKC). J Clin Pathol 57:411–416

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Gall J, Kass-Eisler A, Leinwand L, Falck-Pedersen E (1996) Adenovirus type 5 and 7 capsid chimera: fiber replacement alters receptor tropism without affecting primary immune neutralization epitopes. J Virol 70:2116–2123

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Walsh MP, Chintakuntlawar A, Robinson CM, Madisch I, Harrach B, Hudson NR, Schnurr D, Heim A, Chodosh J, Seto D, Jones MS (2009) Evidence of molecular evolution driven by recombination events influencing tropism in a novel human adenovirus that causes epidemic keratoconjunctivitis. PLoS One 4:e5635

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

This study was supported by the Tunisian Ministry for Scientific Research and Technology, (LR11-IPT09).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Nadia Fedaoui.

Ethics declarations

Conflict of interest

Nadia Fedaoui declares that she has no conflict of interest. Narjess Ben Ayed declares that she has no conflict of interest. Ahlem Ben Yahia declares that she has no conflict of interest. Walid Hammami declares that he has no conflict of interest. Henda Touzi declares that she has no conflict of interest. Henda Triki declares that she has no conflict of interest.

Ethical approval

Ethical clearance to conduct this study was not required because this work was conducted within the routine investigation of patients for the diagnosis of viral conjunctivitis.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fedaoui, N., Ayed, N.B., Yahia, A.B. et al. Genetic variability of human adenovirus type 8 causing epidemic and sporadic cases of keratoconjunctivitis. Arch Virol 161, 1469–1476 (2016). https://doi.org/10.1007/s00705-016-2804-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00705-016-2804-0

Keywords

Navigation