Document 3309
 DOCN  M94A3309
 TI    Role of HIV as cofactor in HPV oncogenesis.
 DT    9412
 AU    Tornesello ML; Buonaguro FM; Del Gaudio E; Buonaguro L; Beth-Giraldo E;
       Giraldo G; Div. of Viral Oncology, Ist. Naz. Tumori Fond. Pascale,
       Naples,; Italy.
 SO    Int Conf AIDS. 1994 Aug 7-12;10(1):105 (abstract no. PA0037). Unique
       Identifier : AIDSLINE ICA10/94369266
 AB    OBJECTIVE: The increased incidence in AIDS patients of Human
       Papillomavirus (HPV) associated lesions stimulated our studies to
       determine the role of HIV on HPV and to identify the molecular
       mechanisms involved in such interaction. We have previously shown that
       HIV-1 Tat transactivates the HPV16 Long Control Region (LCR) (M.L.
       Tornesello et al., Intervirology 1993). The aim of this report is to
       show the in vitro effect of Tat protein on the transforming activity of
       HPV16 E6 and E7 genes. METHODS: NIH3T3 fibroblast cells are infected
       with amphotropic retroviruses transducing the HPV16 E6 and E7 genes
       driven by a costitutively high expressing promoter (LTR) or by the
       Tat-inducible HPV16 LCR enhancer/promoter (LXSN/E6E7 and LXSN/LCRE6E7
       respectively). Infected cells are transfected with a Tat expressing
       vector or with mock DNA. Transformed foci, obtained with or without Tat
       are characterized by Southern and Northern blot analysis. RESULTS: Both
       retroviral constructs expressing E6 and E7 genes induced a 15- to
       17.5-fold increase in the number of foci per surviving cells versus
       NIH3T3 cells transduced with the prototype retrovirus. Tat transfection
       induced an average 40% increment of foci in both E6/E7 and LCR/E6/E7
       retroviruses infected cells. The molecular characterization of
       transformed cells will be presented. DISCUSSION AND CONCLUSION: We have
       demonstrated that a) Tat protein can modify the expression of HPV E6 and
       E7, and b) Tat protein increases the transformation activity of both
       retroviral constructs expressing the E6 and E7 genes. In conclusion
       these in vitro results suggest that HIV, besides its immunosuppression
       activity, may be directly involved, through HPV regulation, in the
       increase of anogenital dysplasia observed in AIDS patients.
 DE    Animal  Gene Expression  Gene Products, tat/GENETICS/PHYSIOLOGY  Genes,
       tat  Genes, Viral  Human  HIV-1/GENETICS/*PATHOGENICITY  In Vitro  Mice
       Papillomavirus, Human/GENETICS/*PATHOGENICITY  Papovaviridae
       Infections/*ETIOLOGY  Transfection  Tumor Virus Infections/*ETIOLOGY
       3T3 Cells/MICROBIOLOGY  MEETING ABSTRACT

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