Augmentation of reverse transcription by integrase through an interaction with host factor, SIP1/Gemin2 Is critical for HIV-1 infection.
There has been accumulating evidence for the involvement of retroviral integrase (IN) in the reverse transcription of viral RNA. We previously identified a host factor, survival motor neuron-interacting protein 1 (SIP1/Gemin2) that binds to human immunodeficiency virus type 1 (HIV-1) IN and supports HIV-1 infection apparently at reverse transcription step. Here, we demonstrated that HIV-1 IN together with SIP1 augments reverse transcriptase (RT) activity by enhancing the assembly of RT on viral RNA in vitro. Synthetic peptides corresponding to the binding motifs within IN that inhibited the IN-SIP1 interaction abrogated reverse transcription in vitro and in vivo. Furthermore, knockdown of SIP1 reduced intracellular stability and multimer formation of IN through proteasome-mediated degradation machinery. Taken together, SIP1 appears to stabilize functional multimer forms of IN, thereby promoting the assembly of IN and RT on viral RNA to allow efficient reverse transcription, which is a prerequisite for efficient HIV-1 infection.
Nishitsuji
Hironori
H
Department of Immunotherapeutics, Graduate School of Medicine and Dentistry, Tokyo Medical and Dental University, Tokyo, Japan.
Hayashi
Takaya
T
Takahashi
Takuya
T
Miyano
Masashi
M
Kannagi
Mari
M
Masuda
Takao
T
D020816:Amino Acid Motifs; D002460:Cell Line; D015658:HIV Infections / Q000378:metabolism* / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics*; D006801:Humans; D047468:Immunoprecipitation; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010455:Peptides / Q000737:chemistry; D010957:Plasmids / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry; D048348:Reverse Transcription
C108381:GEMIN2 protein, human; D009419:Nerve Tissue Proteins; D010455:Peptides; D034741:RNA, Small Interfering; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D011994:Recombinant Proteins; D019427:HIV Integrase; D046988:Proteasome Endopeptidase Complex