Global analysis of cellular transcription following infection with an HIV-based vector.
We have examined the changes in cellular transcription resulting from infection with HIV-based vectors. Previous work suggested that the incoming viral genome may under some circumstances be detected as DNA damage, so to explore this possibility, we compared the transcriptional response to infection with an HIV-based vector to the response to treatment with the DNA-damaging agent etoposide. Expression levels of about 12,000 cellular RNA transcripts were determined in a human B-cell line at different times after either treatment. Statistical analysis revealed that the infection with the lentivirus vector resulted in quite modest changes in gene expression. Treatment with etoposide, in contrast, caused drastic changes in expression of genes known or inferred to be involved in apoptosis. Statistically significant though subtle parallels in the cellular transcriptional responses to etoposide treatment and HIV-vector infection could be detected. Several further data sets analyzing infections with HIV-based vectors or wild-type HIV-1 showed similar modest effects on cellular transcription and very modest parallels among different data sets. These findings establish that HIV-vector or HIV-1 infection has remarkably little effect on cellular transcription. The statistical methods described here may be of wide use in mining microarray data sets. Our observations support the idea that gene therapy with HIV-based vectors should not be particularly toxic to cells due to disruption of cellular transcription.
Mitchell
Richard
R
Infectious Disease Laboratory, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Chiang
Chih-Yuan
CY
Berry
Charles
C
Bushman
Frederic
F
D001402:B-Lymphocytes / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology; D020869:Gene Expression Profiling; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D006678:HIV; D006801:Humans; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010802:Phylogeny
D019384:Nucleic Acid Synthesis Inhibitors; D005047:Etoposide