title: Tat RNA silencing suppressor activity contributes to perturbation of lymphocyte miRNA by HIV-1.
abstract: BACKGROUND
  MicroRNA (miRNA)-mediated RNA silencing is integral to virtually every cellular process including cell cycle progression and response to virus infection. The interplay between RNA silencing and HIV-1 is multifaceted, and accumulating evidence posits a strike-counterstrike interface that alters the cellular environment to favor virus replication. For instance, miRNA-mediated RNA silencing of HIV-1 translation is antagonized by HIV-1 Tat RNA silencing suppressor activity. The activity of HIV-1 accessory proteins Vpr/Vif delays cell cycle progression, which is a process prominently modulated by miRNA. The expression profile of cellular miRNA is altered by HIV-1 infection in both cultured cells and clinical samples. The open question stands of what, if any, is the contribution of Tat RNA silencing suppressor activity or Vpr/Vif activity to the perturbation of cellular miRNA by HIV-1.
  
  
  RESULTS
  Herein, we compared the perturbation of miRNA expression profiles of lymphocytes infected with HIV-1(NL4-3) or derivative strains that are deficient in Tat RNA silencing suppressor activity (Tat K51A substitution) or ablated of the vpr/vif open reading frames. Microarrays recapitulated the perturbation of the cellular miRNA profile by HIV-1 infection. The miRNA expression trends overlapped ~50% with published microarray results on clinical samples from HIV-1 infected patients. Moreover, the number of miRNA perturbed by HIV-1 was largely similar despite ablation of Tat RSS activity and Vpr/Vif; however, the Tat RSS mutation lessened HIV-1 downregulation of twenty-two miRNAs.
  
  
  CONCLUSIONS
  Our study identified miRNA expression changes attributable to Tat RSS activity in HIV-1(NL4-3). The results accomplish a necessary step in the process to understand the interface of HIV-1 with host RNA silencing activity. The overlap in miRNA expression trends observed between HIV-1 infected CEMx174 lymphocytes and primary cells supports the utility of cultured lymphocytes as a tractable model to investigate interplay between HIV-1 and host RNA silencing. The subset of miRNA determined to be perturbed by Tat RSS in HIV-1 infection provides a focal point to define the gene networks that shape the cellular environment for HIV-1 replication.
authors.affiliation: Department of Veterinary Biosciences, Center for Retrovirus Research, Ohio State University, Columbus OH, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Hayes
authors.forename: Shuiming
authors.initials: S
authors.lastname: Qian
authors.forename: Lianbo
authors.initials: L
authors.lastname: Yu
authors.forename: Kathleen
authors.initials: K
authors.lastname: Boris-Lawrie
mesh_terms: D002478:Cells, Cultured; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015497:HIV-1 / Q000276:immunology* / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D008214:Lymphocytes / Q000276:immunology* / Q000821:virology*; D035683:MicroRNAs / Q000096:biosynthesis*; D046228:Microarray Analysis; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*; D054320:vif Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D037521:Virulence Factors; D054322:tat Gene Products, Human Immunodeficiency Virus; D054320:vif Gene Products, Human Immunodeficiency Virus; C514847:vif protein, Human immunodeficiency virus 1; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1