Takeshi Yoshida: Department of Molecular Virology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address: takeshi-yoshida@umin.ac.jp.
Akiko Hamano: Department of Molecular Virology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Asuka Ueda: Department of Molecular Virology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Hiroaki Takeuchi: Department of Molecular Virology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Shoji Yamaoka: Department of Molecular Virology, Tokyo Medical and Dental University (TMDU), Tokyo, Japan. Electronic address: shojmmb@tmd.ac.jp.
Human SMOOTHENED (SMO) was identified by expression cloning as a new host factor that inhibits HIV-1 infection. Forced expression of SMO inhibited HIV-1 replication and infection with a single-round lentiviral vector, but not infection with a murine leukemia virus-based retroviral vector in human MT-4 T cells. Quantitative PCR analyses revealed that stable expression of SMO impaired formation of the integrated form of lentiviral DNA, but did not interrupt reverse transcription. This inhibition was evident in MT-4 and HUT102 human T cell lines expressing low levels of SMO mRNA, but not in SupT1 or Jurkat T cell lines expressing higher levels of SMO mRNA. Depletion of SMO mRNA in Jurkat cells facilitated HIV-1 vector infection, suggesting that endogenous SMO plays a role in limiting lentiviral infection. These results suggest that SMO inhibits HIV-1 replication after completion of reverse transcription but before integration.
