Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
THE HIV TAT GENE TRANSFORMS HUMAN EPIDERMAL KERATINOCYTES IN CULTURE (MEETING ABSTRACT)
Fifteenth Symposium of the International Association for Comparative Research on Leukemia and Related Disease. October 6-11, 1991, Padova/Venice, Italy, p. 76, 1991.. Unique Identifier : AIDSLINE ICDB/92682417 Rhim JS; Kim CM; Vogel J; Jay G; NCI, Bethesda, MD 20892
Abstract:
Patients with AIDS develop a wide range of cutaneous disorders, such as squamous cell and basal cell carcinomas, Kaposi's sarcoma and non-neoplastic lesions, including psoriasis and seborrheic dermatitis. Since these individuals are frequently infected not only by HIV but also by other agents including the human papilloma virus, it is not clear whether the development of any of these skin manifestations is directly attributable to HIV. Human epidermal keratinocytes (HEK) are known to express HLADR molecules which are involved in HIV binding and have recently been shown to be susceptible to HIV infection. Since many of the cutaneous manifestations are accompanied by an early onset of epidermal hyperplasia, the keratinocyte is a strong candidate for infection by the virus, given that the presence of the CD4 receptor is not a prerequisite for HIV entry into the cell. We now report that the HIV tat gene, under the control of the viral long terminal repeat (LTR), can efficiently transform HEK in culture. We chose to study tat because a similar gene from a different human retrovirus, the tat gene of HTLV-1, has previously been shown to have transforming activity on appropriate target cells, namely T cells and fibroblasts. Nontumorigenic, immortalized HEK line (RHEK-1) was cotransfected with the LTR-tat gene and the pSV2-neo gene. Of 25 neomycin-resistant clones, at least 7 were found by Southern blot hybridization analysis to contain LTR-tat DNA sequences stably integrated into the host cell genome. By reverse transcriptase-polymerase chain reaction analysis, 5 of the clones were found to express tat-specific mRNA. All 5 clones were found to be tumorigenic in nude mice. Control RHEK-1 cells and random neomycin-resistant and tat-negative clones were nontumorigenic. While control RHEK-1 cells and tat-negative clones were flat, the tat-positive clones were altered with the exception of 1 clone. Further, the tat-expressing clones had higher cloning efficiency and larger colony size in soft agar. This study provides direct evidence for the ability of the HIV tat gene to transform HEK in culture. Given our previous observations in transgenic mice that the same LTR-tat gene was expressed in the epidermis and induced extensive epidermal hyperplasia, the present finding strongly suggests that keratinocytes may very well be a target for HIV infection in humans.
Keywords: *Cell Transformation, Neoplastic Cells, Cultured Drug Resistance Gene Products, tat/*PHARMACOLOGY Human HIV Infections/*PATHOLOGY HIV Long Terminal Repeat Keratinocytes/*CYTOLOGY Neomycin/PHARMACOLOGY RNA, Messenger/METABOLISM ABSTRACT 920930
M9290915
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Important note: Information in this article was accurate in 1992. The state of the art may have changed since the publication date.
