title: HIV-1 replication and latency are regulated by translational control of cyclin T1.
abstract: Human immunodeficiency virus (HIV) exploits cellular proteins during its replicative cycle and latent infection. The positive transcription elongation factor b (P-TEFb) is a key cellular transcription factor critical for these viral processes and is a drug target. During viral replication, P-TEFb is recruited via interactions of its cyclin T1 subunit with the HIV Tat (transactivator of transcription) protein and TAR (transactivation response) element. Through RNA silencing and over-expression experiments, we discovered that nuclear factor 90 (NF90), a cellular RNA binding protein, regulates P-TEFb expression. NF90 depletion reduced cyclin T1 protein levels by inhibiting translation initiation. Regulation was mediated by the 3' untranslated region of cyclin T1 mRNA independently of microRNAs. Cyclin T1 induction is involved in the escape of HIV-1 from latency. We show that the activation of viral replication by phorbol ester in latently infected monocytic cells requires the posttranscriptional induction of NF90 and cyclin T1, implicating NF90 in protein kinase C signaling pathways. This investigation reveals a novel mechanism of cyclin T1 regulation and establishes NF90 as a regulator of HIV-1 replication during both productive infection and induction from latency.
authors.affiliation: Department of Biochemistry and Molecular Biology, UMDNJ-New Jersey Medical School, PO Box 1709, Newark, NJ 07101-1709, USA.
authors.forename: Mainul
authors.initials: M
authors.lastname: Hoque
authors.forename: Raghavendra A
authors.initials: RA
authors.lastname: Shamanna
authors.forename: Deyu
authors.initials: D
authors.lastname: Guan
authors.forename: Tsafi
authors.initials: T
authors.lastname: Pe'ery
authors.forename: Michael B
authors.initials: MB
authors.lastname: Mathews
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D056906:Cyclin T / Q000235:genetics* / Q000378:metabolism; D042863:Cyclin-Dependent Kinase 9 / Q000235:genetics; D015967:Gene Expression Regulation, Viral; D055785:Gene Knockdown Techniques; D016655:HIV Core Protein p24 / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D050779:Nuclear Factor 90 Proteins / Q000378:metabolism; D042925:Positive Transcriptional Elongation Factor B / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D014176:Protein Biosynthesis; D014158:Transcription, Genetic; D017735:Virus Latency / Q000235:genetics / Q000502:physiology*; D014779:Virus Replication / Q000502:physiology*
chemical_list: D020413:3' Untranslated Regions; C503684:CCNT1 protein, human; D056906:Cyclin T; D016655:HIV Core Protein p24; D050779:Nuclear Factor 90 Proteins; C514799:p24 protein, Human Immunodeficiency Virus Type 1; D042925:Positive Transcriptional Elongation Factor B; C467969:CDK9 protein, human; D042863:Cyclin-Dependent Kinase 9