Journal of Medical Virology 75:440–446 (2005) Molecular Epidemiology of Adenovirus Strains Isolated From Patients With Ocular Disease in the Area of Thessaloniki, Greece (1998–2002) Filanthi Frantzidou, 1 * Aikaterini Pavlitou, 1 Asimina Mataftsi, 2 Kamal Dumaidi, 1 and Nikolaos Georgiadis 2 1 A’ Department of Microbiology, School of Medicine, Aristotle University of Thessaloniki, Greece 2 Eye Clinic, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, Greece Thirty strains of adenovirus (Ads) associated with ocular disease have been isolated over a period of 4 years in Thessaloniki, Northern Greece. Eleven strains were isolated from sporadic patients with conjunctivitis or keratoconjunctivi- tis in Thessaloniki city between 1998 and 2000. Nineteen strains were isolated from patients with keratoconjunctivitis during an outbreak of Ads in the area of Thessaloniki (Thessaloniki and Serres cities) in 2002. PCR-sequence method using primers targeted against the hypervariable regions (HVRs) of hexon gene, as well as the neutralization test were used for typing the Ad isolates and assessing a possible relation among these strains, and their genetic variability. Ad4 with very close homology to variant Z-G 95-873 was the most frequent genotype causing spora- dic conjunctivitis over a period of 4 years. Two other strains, one Ad2, and one Ad3 were similar to the prototype ones, and a third one shows close homology to the variant of prototype Ad15, the Morrison strain. The genome typing of twenty two Ad8 isolates showed very close homology in their amino acid and nucleotide sequences to the variant of Ad8, strain 1127 (accession no. X74663). Four were isolated from patients with keratoconjunctivitis in 1998, 1999, 2000 and 18 during the outbreak in 2002. As far as strain 1127 is concerned, all the Ad8 isolates showed the same changes in the HVR 1 and HVR 2 except one isolate in 1998, which showed some changes outside the HVRs. During the outbreak of Ad8 keratoconjunctivitis, it was not possible to iden- tify the exact source of infection (nosocomial or/ and outpatients). Finally, Ad4 variant Z-G 95-873 and Ad8 which is closely related to the strain 1127, were found to be the predominant adeno- viruses circulating in Northern Greece during 1998–2002. J. Med. Virol. 75:440 – 446, 2005. ß 2005 Wiley-Liss, Inc. KEY WORDS: Greece; adenovirus; (kerato)- conjunctivitis; outbreak; poly- merase chain reaction with sequencing analysis; genome typing INTRODUCTION To date, 51 different serotypes of adenoviruses (Ads) have been identified [de Jong et al., 1999]. They are classified into six subgenera, A – F, on the basis of nucleic acid differences, fiber protein characteristics, and bio- logical properties [Wadell et al., 1986; Murphy et al., 1995]. The principal adenovirus types 2, 3, 4, 6, 7, 8, 19, and 37 have been found to be responsible for the majority of ocular infections. Acute conjunctivitis may occur as part of a pharyngo-conjunctivitis syndrome or as sepa- rate entity. The most frequently encountered types are adenovirus 3 (subgenus B), and adenovirus 4 (subgenus E). Other types such as adenovirus 1, 2, and 6 (subgenus C) and 9, 10, 15, 17, 20, 22, 29 (subgroup D) and ad- enovirus 7,16 of subgroup B have been reported to cause conjunctivitis. Adenovirus type 4 is a significant cause of outbreak of respiratory disease among military recruits, but it has also been associated with follicular conjuncti- vitis [Aoki et al., 1982; Cooper et al., 1993; Schepetiuk et al., 1993]. In Western countries adenoviral conjuncti- vitis is frequently reported as swimming pool conjuncti- vitis or nosocomial conjunctivitis. Certain members of subgenus D, namely the Ad8, Ad19a, and Ad37, cause outbreaks of keratoconjunctivitis and rapid identifi- cation of these serotypes can help in prevention and *Correspondence to: Filanthi Frantzidou, A’ Department of Microbiology, School of Medicine, Aristotle University of Thessa- loniki, Thessaloniki 54124. E-mail: filanthi@med.auth.gr Accepted 25 November 2004 DOI 10.1002/jmv.20286 Published online in Wiley InterScience (www.interscience.wiley.com) ß 2005 WILEY-LISS, INC.