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M94A3309.TXT
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1994-10-25
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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
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).