AEGiS-07IAC: c-sis/PDGFB is transcribed in primary lymphocytes exposed to HTLV-1: a possible role for the PDGF autocrine circuit in the control of proliferation in infected cells.

7th International AIDS Conference

Florence, Italy — June 16-21, 1991

c-sis/PDGFB is transcribed in primary lymphocytes exposed to HTLV-1: a possible role for the PDGF autocrine circuit in the control of proliferation in infected cells.

Int Conf AIDS 1991 Jun 16-21; 7:28 (abstract no. M.A.27)
D'Onofrio C, Faraoni I, Macchi B, Bonmassar E; Dept. Exp. Med. Biochem. Sci., II University of Rome, Rome, Italy

OBJECTIVE: PDGF has been described not to be expressed in T lymphocytes under physiological conditions. More recently, PDGFB and its receptor have been found to be expressed in T cell lines infected with HTLV-I (D'Onofrio et al., J. IFN Res.9(2s):S82, 1989; Goustin et al., Growth Factors 2:189, 1990). These data suggest that the c-sis protoncogene/PDGFB, a highly mitogenic factor, could play a main role in the control of proliferation of virus-infected cells, possibly contributing to cellular transformation. To elucidate this point, HTLV-I mediated expression of c-sis/PDGFB was studied in primary cord blood-derived momonuclear cells (CBMC) and in CD4+ and CD8+ isolated T lymphocyte subsets.

METHODS: CBMC were isolated by Ficoll-Paque gradients and further separated, depending on their phenotype markers, by immunomagnetic microbeads conjugated with specific monoclonal antibodies. Amplification of c-sis in the genome of CBMC, cocultured with lethally irradiated MT-2 virus-donor cells, was evaluated by Southern blots. Expression of c-sis was evaluated as mRNA transcription during culture time following exposure to HTLV-I (Northern and dot blots) and as indirect immunofluorescence for the PDGFB protein in infected cells (double immunofluorescence staining).

RESULTS: No amplification of c-sis/PDGFB was observed in CBMN/MT-2 cocultures, 1 week post infection (p.i). This gene was not transcribed in early hours p.i., whereas mRNA transcripts were present 5 days p.i. Similarly, c-sis/PDGFB was transcribed in cocultured CD4+ and CD8+ subsets, 1-2 weeks, p.i. Interferon-beta, which has been previously shown to inhibit early transcription of HTLV-I in infected cells, down-regulated the expression of c-sis in cocultured cells.

CONCLUSIONS: c-sis/PDGFB can be expressed also in cells of the lymphocytic lineage, not only in monocytes, platelets and progenitor cells, as previously known. Its expression is associated with exposure of lymphocytes to HTLV-I and is down-regulated by interferon beta, which in turn can inhibit infection of recipient cells. The role of PDGFB in the control of cell cycle progression in infected CBMC is presently under evaluation.

Keywords: AEGIS, Human T-lymphotropic virus 1, Proto-Oncogene Proteins c-sis, Platelet-Derived Growth Factor, Genes, sis, T-Lymphocytes, Proto-Oncogenes, Lymphocyte Activation, Receptors, Platelet-Derived Growth Factor, Interferon-beta, Transcription, Genetic, RNA, Messenger, Cell Line, Coculture, genetics, immunology, ICA7
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