Document 0597
 DOCN  M9550597
 TI    Differential effects of human cytomegalovirus on integrated and
       unintegrated human immunodeficiency virus sequences.
 DT    9505
 AU    Koval V; Jault FM; Pal PG; Moreno TN; Aiken C; Trono D; Spector SA;
       Spector DH; Department of Biology, University of California, San Diego,
       La; Jolla 92093-0116.
 SO    J Virol. 1995 Mar;69(3):1645-51. Unique Identifier : AIDSLINE
       MED/95156592
 AB    Human cytomegalovirus (HCMV) has been implicated as a potential cofactor
       in human immunodeficiency virus type 1 (HIV-1)-related disease.
       Previously, we reported that HCMV inhibits HIV-1 RNA and protein
       synthesis in cells productively infected with both viruses but, in
       transient assays, activates an HIV-1 long terminal
       repeat-chloramphenicol acetyltransferase (LTR-CAT) construct introduced
       into the cell by transfection (V. Koval, C. Clark, M. Vaishnav, S. A.
       Spector, and D. H. Spector, J. Virol. 65:6969-6978, 1991). We show here
       that HCMV can also activate an infectious proviral HIV-1 genome
       transiently transfected into a cell. To ascertain whether integration of
       the HIV-1 provirus plays a role in these differential effects, we
       generated monoclonal and polyclonal cell lines that each contain a
       single integrated copy of an HIV-1 LTR-CAT construct and compared the
       regulatory effects of HCMV and HIV-1 infection in these cells with those
       occurring in the same type of cell transiently transfected with the
       HIV-1 LTR-CAT construct. We find that HCMV activates the transfected
       HIV-1 promoter 230-fold but activates the integrated promoter only 2.8-
       to 54-fold. In contrast, HIV-1 stimulates the integrated HIV-1 promoter
       2,700- to 6,000-fold but stimulates the transfected promoter only
       80-fold. Thus, the relative response of the HIV-1 promoter to HCMV and
       HIV-1 regulatory proteins depends upon whether it is integrated. To
       determine if HIV-1 gene products are necessary for the HCMV-mediated
       repression, we constructed cell lines containing two different stably
       integrated HIV-1 proviruses: one is tat- and nef-minus and
       transcriptionally inactive, while the other is env- and nef-minus but
       actively expresses the other HIV-1 gene products. Upon infection with
       HCMV, HIV-1 antigen production was stimulated from the inactive HIV-1
       genome but inhibited from the active genome. We propose that HCMV has
       two separate effects on HIV-1 replication during a coinfection. One is a
       slight stimulatory effect which would be undetectable during an active
       HIV-1 infection, while the other is a net inhibitory effect that is
       mediated by an interaction between HCMV and HIV-1 gene products.
 DE    Cell Line  Cytomegalovirus/*GENETICS  *Gene Expression Regulation, Viral
       Genes, env  Genes, tat  Human  HIV/GROWTH & DEVELOPMENT/*GENETICS  In
       Vitro  Proviruses/GENETICS  Repetitive Sequences, Nucleic Acid  RNA,
       Messenger/GENETICS  Support, U.S. Gov't, P.H.S.  Virus Integration
       *Virus Replication  JOURNAL ARTICLE

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