Cellular gene expression upon human immunodeficiency virus type 1 infection of CD4(+)-T-cell lines.
The expression levels of approximately 4,600 cellular RNA transcripts were assessed in CD4(+)-T-cell lines at different times after infection with human immunodeficiency virus type 1 strain BRU (HIV-1(BRU)) using DNA microarrays. We found that several classes of genes were inhibited by HIV-1(BRU) infection, consistent with the G(2) arrest of HIV-1-infected cells induced by Vpr. These included genes involved in cell division and transcription, a family of DEAD-box proteins (RNA helicases), and all genes involved in translation and splicing. However, the overall level of cell activation and signaling was increased in infected cells, consistent with strong virus production. These included a subgroup of transcription factors, including EGR1 and JUN, suggesting they play a specific role in the HIV-1 life cycle. Some regulatory changes were cell line specific; however, the majority, including enzymes involved in cholesterol biosynthesis, of changes were regulated in most infected cell lines. Compendium analysis comparing gene expression profiles of our HIV-1 infection experiments to those of cells exposed to heat shock, interferon, or influenza A virus indicated that HIV-1 infection largely induced specific changes rather than simply activating stress response or cytokine response pathways. Thus, microarray analysis confirmed several known HIV-1 host cell interactions and permitted identification of specific cellular pathways not previously implicated in HIV-1 infection. Continuing analyses are expected to suggest strategies for impacting HIV-1 replication in vivo by targeting these pathways.
van 't Wout
Angélique B
AB
Department of Microbiology, University of Washington School of Medicine, Seattle 98195-8070, USA. vantwout@u.washington.edu
Lehrman
Ginger K
GK
Mikheeva
Svetlana A
SA
O'Keeffe
Gemma C
GC
Katze
Michael G
MG
Bumgarner
Roger E
RE
Geiss
Gary K
GK
Mullins
James I
JI
D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002460:Cell Line; D017931:DNA Primers; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers