3형 아데노바이러스의 면역조절 유전자 다양성

Genetic Variation in the Immunoregulatory Gene of Adenovirus Type 3

  • 최은화 (서울대학교 의과대학 소아과학교실) ;
  • 김희섭 (동국대학교 의과대학 소아과학교실) ;
  • 이환종 (서울대학교 의과대학 소아과학교실)
  • Choi, Eun Hwa (Department of Pediatrics, Seoul National University College of Medicine) ;
  • Kim, Hee Sup (Department of Pediatrics, College of Medicine, Dongguk University) ;
  • Lee, Hoan Jong (Department of Pediatrics, Seoul National University College of Medicine)
  • 투고 : 2009.11.30
  • 심사 : 2009.12.10
  • 발행 : 2009.12.25

초록

목 적: 아데노바이러스 early region 3 (E3) 유전자 단백은 세포독성 세포와 다양한 싸이토카인이 매개하는 세포파괴를 저해하는 기능을 한다. 본 연구는 E3 유전자의 다양성이 아데노바이러스의 분자생물학적 다양성을 설명할 수 있는지 밝히기 위하여 시행되었다. 방 법: 1990년부터 2000년까지 10년 동안 서울대학교 어린이병원에서 하기도 감염증으로 치료받은 소아로부터 분리 된 3형 아데노바이러스 14 주를 대상으로 하여 E3 유전자의 변이와 유전체형과의 연관성을 분석하였다. 결 과: 3형 아데노바이러스의 E3 유전자는 표준 주(M15952)와 비교하여 98%의 일치도를 보였으며, 국내 분리 주간의 일치도는 98.7%이었다. 아미노산 서열의 변이는 20.1 kDa, 20.6kDa, truncated 7.7 kDa, 10.3 kDa, 14.9 kDa, 그리고 15.3kDa에 나타났다. 또한, 14 주 모두에서 truncated 7.7 kDa의 시작 코돈에 missense 변이가 있었으며, 58개(10주) 혹은 94개(4주)의 염기쌍이 소실되는 변이가 동반되었다. 유전체형에 따른 E3 유전자의 변이는 대개 유전체형에 특이하게 나타나 연관성이 높은 것을 알 수 있었다. 결 론: 3형 아데노바이러스 주의 면역기능 조절 유전자 E3의 다양성은 유전체형과의 연관성이 높은 것으로 나타났다.

Purpose : Various proteins encoded in the early region 3 (E3) of adenoviruses protect cells from being killed by cytotoxic T cells and death-inducing cytokines. We sought to find out whether the genetic heterogeneity of the E3 gene might contribute to the molecular diversity of adenoviruses. Methods : Sequences in the E3 region were analyzed for 14 adenovirus type 3 (Ad3) strains that were isolated from children with lower respiratory tract infections in the Seoul National University Children's Hospital during the period 1991-2000. Full-length adenoviral DNA was purified from the infected A549 cell lysates using a modified Hirt procedure. Results : There was 98% homology between 14 Korean Ad3 strains with a reference strain (M15952). Homology within the Korean Ad3 strains was 98.7%. Variation was found in the region of transcripts 20.1 kDa, 20.6 kDa, truncated 7.7 kDa, 10.3 kDa, 14.9 kDa, and 15.3 kDa. In particular, all 14 Korean strains showed a missense single point mutation at the start codon of the truncated 7.7 kDa. In addition, a deletion was found in the truncated 7.7 kDa region by 58 base pairs in 10 strains and 94 base pairs in 4 strains. Variations in amino acids were observed in the receptor internalization and degradation complex (10.3 kDa/14.9 kDa) which stimulates the clearance from the cell surface and subsequent degradation of the receptors for the Fas ligand and TRAIL, while no variations were observed in another immunoregulatory transcript, 19 kDa. Conclusion : Sequence analysis of the immunoregulatory region of adenovirus E3 shows that genetic heterogeneities are related to genome type patterns.

키워드

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