Korean Journal of Microbiology (미생물학회지)

The Microbiological Society of Korea (한국미생물학회)
권호 표지

The Infectivity of Recombinant Porcine Endogenous Retrovirus (PERV-A/C) Is Modulated by Membrane-Proximal Cytoplasmic Domain of PERV-C Envelope Tail

C형 돼지 내인성 레트로바이러스(PERV)의 C-말단 외막당단백질에 의한 재조합 PERV-A/C의 감염력 조절

  • Kim, Sae-Ro-Mi (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Park, Sang-Min (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Lee, Kyu-Jun (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Lee, Yong-Jin (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Bae, Eun-Hye (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Park, Sung-Han (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Lim, Ji-Hyun (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University) ;
  • Jung, Yong-Tae (Department of Microbiology and Institute of Basic Science, College of Advanced Science, Dankook University)
  • 김새로미 (단국대학교 첨단과학대학 미생물학과) ;
  • 박상민 (단국대학교 첨단과학대학 미생물학과) ;
  • 이규준 (단국대학교 첨단과학대학 미생물학과) ;
  • 이용진 (단국대학교 첨단과학대학 미생물학과) ;
  • 배은혜 (단국대학교 첨단과학대학 미생물학과) ;
  • 박성한 (단국대학교 첨단과학대학 미생물학과) ;
  • 임지현 (단국대학교 첨단과학대학 미생물학과) ;
  • 정용태 (단국대학교 첨단과학대학 미생물학과)
  • Received : 2009.12.07
  • Accepted : 2010.01.27
  • Published : 2010.03.31
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Abstract

Xenotransplantation of pig organs is complicated by the existence of polytropic replication-competent porcine endogenous retroviruses (PERV) capable of infecting human cells. Two classes of infectious human-tropic replication-competent PERVs (PERV-A and PERV-B) and one class of ecotropic PERV-C are known. The potential for recombination between ecotropic PERV-C and human-tropic PERVs adds another level of infectious risk. A recombinant PERV-A/C (PERV-A14/220) virus is 500-fold more infectious than PERV-A. Two determinants of this high infectivity was identified; one was isoleucine-to-valine substitution at position 140 in RBD (receptor binding domain), and the other lies within the PRR (proline rich region) of the envelope protein. To examine whether the effects of the cytoplasmic tail of the PERV-C Env on fusogenesity also influences infectivity, we constructed a pseudotype retroviral vectors containing MoMLV core protein and PERV envelopes. Pseudotyping experiments with the PERV envelope glycoproteins indicated that recombinant PERV-A/C virus is 10-fold more infectious than PERV-A by lacZ staining. This result supports the suggestion that viral transduction of PERV-A/C is enhanced by a membrane-proximal cytoplasmic amphiphilic ${\alpha}$-helix in PERV-C Env tail.

돼지를 이용한 이종간 장기이식은 인간 세포주를 감염시킬 수 있는 것으로 알려진 돼지 내인성 레트로바이러스의 존재로 인해 실제 적용에 어려움이 있다. PERV (Porcine Endogenous Retrovirus: PERV)-A와 PERV-B는 in vitro 상에서 인간 세포주와 돼지 세포주를 동시에 감염시킬 수 있으나 PERV-C는 단지 돼지 세포주만 감염시킬 수 있다. 또한 PERV-A와 PERV-B 또는 PERV-A와 PERV-C사이에 재조합이 일어나 새로운 위험한 바이러스가 출현할 가능성이 있다. 최초의 재조합 바이러스인 PERV-A14/220은 대부분 PERV-C의 유전자로 구성 되어있으며 수용체와 결합하는 부위만 PERV-A의 외막 유전자로 재조합이 되어 있는데 PERV-A보다 500배 이상 높은 감염가를 가진다. PERV-A14/220의 경우 PERV-A 외막 단백질 140 번째 아미노산과 PERV-C 외막 PRR (proline rich region) 부위가 높은 감염가에 관여하는 것으로 알려져 있다. 본 연구에서는 막 융합에 관여하는 PERV-C의 세포질쪽 C-말단 부위 또한 재조합 바이러스의 높은 감염가에 관여하는지 알아보기 위해 PERV-A/C의 재조합 외막 당단백질을 가진 pseudotype 바이러스를 만들어 사람 세포주에서 감염가를 측정하였는데 PERV-A 보다 재조합 바이러스가 10배 이상 높은 감염가를 나타내었다. 이러한 연구 결과는 PERV-C의 C-말단 막당단백질에 존재하는 양친매성 부위가 재조합 바이러스의 높은 감염가에 관여한 것으로 판단된다.

Keywords

References

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