Document 0632
 DOCN  M94A0632
 TI    Involvement of the c-myb proto-oncogene in HIV-1 gene expression.
 DT    9412
 AU    Churchill MJ; Ramsay RG; Deacon NJ; AIDS Molecular Biology Unit, NCHVR,
       Macfarlane Burnet Centre,; Parkville, Australia.
 SO    Annu Conf Australas Soc HIV Med. 1993 Oct 28-30;5:68 (abstract no. FB3).
       Unique Identifier : AIDSLINE ASHM5/94349023
 AB    Recently it has been shown that the HIV-1 LTR contains a high affinity
       Myb-binding site, (Dasgupta et al, PNAS 1990; 87:8090). The
       proto-oncogene c-myb, is expressed in many cell types including
       hemopoietic cell lines and tissues where it is thought to be associated
       with the regulation of proliferation and differentiation. The expression
       of c-myb in different CD4+ T-cell lines was examined in both cytoplasmic
       mRNA and nuclear protein. Levels of c-myb mRNA determined by Northern
       blot analysis were approximately 10 fold higher in MT-2 cells (an HTLV-1
       transformed line) compared with CEM cells, while unstimulated PBLs
       showed a level 1/10 that of CEM cells. Examination of Myb protein by
       Western blotting (WB) also showed the higher expression of c-myb in MT-2
       cells. Mobility shift assays were used to investigate the DNA binding
       activity of nuclear extract from uninfected and HIV-1 infected MT2 and
       CEM cells. Using a synthetic Myb-binding template, we found that the
       protein levels observed by WB correlate well with DNA binding activity
       using both core Myb responsive element (MBS-1) and HIV-1 LTR Myb
       responsive element (LTR-9) oligonucleotides. Transfection of HIV-1
       infected CEM cells with c-myb expression plasmid pACTC3 increased
       cotransfected HIV LTR driven reporter gene activity and HIV cytopathic
       effect. Antisense oligonucleotides to c-myb mRNA inhibited infection of
       MT-2 cells by HIV-1. These data suggest that the elevated levels of
       c-myb expression in MT-2 cells is a requisite for the rapid kinetics of
       HIV-1 infection and virus production in these cells over other T-cell
       lines.
 DE    Cell Line, Transformed  Gene Expression Regulation, Viral/PHYSIOLOGY
       Human  HIV-1/*GENETICS  Proto-Oncogene Proteins/GENETICS  Proto-Oncogene
       Proteins c-myc/*GENETICS  Repetitive Sequences, Nucleic Acid/*GENETICS
       RNA, Messenger/GENETICS  Virus Replication/GENETICS  MEETING ABSTRACT

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