title: Interleukin-2 inhibits HIV-1 replication in some human T cell lymphotrophic virus-1-infected cell lines via the induction and incorporation of APOBEC3G into the virion.
abstract: IL-2 has been used in culture of primary T cells to maintain cell proliferation. We have previously reported that IL-27 inhibits HIV-1 replication in primary T cells in the presence of IL-2. To gain a better understanding of the mechanisms involved in this inhibitory effect, we attempted to investigate in detail the effects of IL-27 and IL-2 using several cell lines. Unexpectedly, IL-27 did not inhibit HIV-1 in T cell lines, whereas IL-2 inhibited HIV-1 replication in the human T cell lymphotrophic virus (HTLV)-1-transformed T cell lines, MT-2, MT-4, SLB-1, and ATL-2. No effects were seen in HTLV-1-negative cell lines. Utilizing MT-2 cells, we demonstrated that IL-2 treatment inhibited HIV-1 syncytia-inducing ability and dose-dependently decreased supernatant p24 antigen levels by >90%. Using real time PCR and Western blot analysis, we observed that IL-2 treatment induced the host restriction factor, APOBEC3G with accumulation into the lower molecular mass active form as characterized by FPLC. Further analysis revealed that the virus recovered from IL-2-treated MT-2 cells had impaired replication competency. This was found to be due to incorporation of APOBEC3G into the virion despite the presence of Vif. These findings demonstrate a novel role for IL-2 in regulating production of infectious HIV-1 virions in HTLV-1-infected cells through the induction of APOBEC3G.
authors: Laboratory of Human Retrovirology, Frederick National Laboratory for Cancer Research, Frederick, Maryland 21702, USA.
authors: Raphael M
authors: RM
authors: Oguariri
authors: Lue
authors: L
authors: Dai
authors: Joseph W
authors: JW
authors: Adelsberger
authors: Adam
authors: A
authors: Rupert
authors: Randy
authors: R
authors: Stevens
authors: Jun
authors: J
authors: Yang
authors: Dawei
authors: D
authors: Huang
authors: Richard A
authors: RA
authors: Lempicki
authors: Ming
authors: M
authors: Zhou
authors: Michael W
authors: MW
authors: Baseler
authors: H Clifford
authors: HC
authors: Lane
authors: Tomozumi
authors: T
authors: Imamichi
mesh_terms: D000071480:APOBEC-3G Deaminase; D015704:CD4 Antigens / Q000378:metabolism; D002460:Cell Line; D003564:Cytidine Deaminase / Q000235:genetics* / Q000378:metabolism; D004790:Enzyme Induction; D055785:Gene Knockdown Techniques; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000502:physiology*; D009154:Mutation; D034741:RNA, Small Interfering / Q000235:genetics; D019718:Receptors, CXCR4 / Q000378:metabolism; D048348:Reverse Transcription; D017422:Sequence Analysis, DNA; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology*; D015533:Transcriptional Activation; D014779:Virus Replication
chemical_list: D015704:CD4 Antigens; C527276:CXCR4 protein, human; D007376:Interleukin-2; D034741:RNA, Small Interfering; D019718:Receptors, CXCR4; D000071480:APOBEC-3G Deaminase; C464924:APOBEC3G protein, human; D003564:Cytidine Deaminase
keywords: Cytokine; Gamma Chain Cytokines; HIV-1; HTLV-1; Host Defense; Host Restriction Factors; IL-2; Immunology; Interleukin; Viral Replication
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