Cell Cycle Arrest in Human Monocyte Cell Line by Human Cytomegalovirus

인체거대세포바이러스에 의한 인체 단핵구세포의 세포주기 저해

  • Jang, So-Young (School of Life Sciences, Chungbuk National University) ;
  • Kim, Mi-Suk (School of Life Sciences, Chungbuk National University) ;
  • Lee, Chan-Hee (School of Life Sciences, Chungbuk National University)
  • 장소영 (충북대학교 자연과학대학 생명과학부) ;
  • 김미숙 (충북대학교 자연과학대학 생명과학부) ;
  • 이찬희 (충북대학교 자연과학대학 생명과학부)
  • Published : 2008.12.31

Abstract

Monocytic cells in myeloid lineage are known for latent site of HCMV Previous studies have suggested that HCMV regulates cell cycle progression in a variety of cells, but studies in monocytic cells are limited. In this study, we attempted to understand cell cycle changes after HCMV infection in the monocytic cell lines. Flow cytometric analyses using propidium iodide revealed that the proportion of G0-G1 phase was increased and the proportion of S phase decreased in HCMV-infected THP-1 cells, but not in HL-60 cells. BrdU-incorporation assay supported that cell proliferation was inhibited in HCMV-infected THP-1 cells by inhibition of de novo DNA synthesis. Western blot analysis revealed that p21, inhibitor of cell cycle progression from G1 phase to S phase, was induced in HCMV-infected THP-1 cells but not in HL-60 cells. Thus, HCMV inhibited cell pro-liferation by arresting the cell cycle at G0-G1 phase through induction of p21 protein in promocytic THP-1 cells.

마이엘로이드 계열의 단핵세포는 인체세포거대바이러스(human cytomegalovirus, HCMV)의 잠복 부위로 알려져 있다. 다양한 세포에서 HCMV에 의한 세포주기의 촉진 또는 억제에 관한 연구는 많이 있었지만, 단핵세포에서의 연구는 거의 없는 상태이다. 이에 본 연구에서는 단핵세포에 HCMV가 감염되면 세포주기에 어떤 변화가 나타나는지 알아보고자 하였다. Propidium iodide를 이용한 유세포 분석을 통한 세포주기 분석에서 HCMV에 감염된 THP-1 세포에서는 G0-G1기가 증가하고, 그만큼 S가 감소함을 보았다. 반면 HL-60 세포에서는G0-G1기와 S기의 상대적인 비율에 큰 변화가 없었다. BrdU 유입 실험에서 THP-1세포의 DNA 합성이 HCMV 감염에 의해 억제됨을 알 수 있었다. 세포주기의 G1기에서 S기로의 전환을 억제하는 p21 단백질은HCMV에 감염된 THP-1 세포에서는 발현이 유도되었지만 HL-60 세포에서는 거의 발현이 되지 않았다. 따라서 HCMV는 promocyte THP-1 세포에서 p21 단백질의 유도에 의해 세포주기를 G0-G1기에서 억류함에 따라 세포중식을 억제하는 것으로 생각된다.

Keywords

References

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