期刊
JOURNAL OF VIROLOGY
卷 81, 期 19, 页码 10515-10523出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/JVI.00947-07
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资金
- NCI NIH HHS [CA70018, R01 CA070018] Funding Source: Medline
- NIAID NIH HHS [AI28697, AI43190, R01 AI043190, P30 AI028697] Funding Source: Medline
Unintegrated human immunodeficiency virus (HIV) DNA are viral DNA products formed naturally during HIV replication. While the integrated proviral DNA form is transcriptionally active and results in productive infection, unintegrated DNA is also capable of expression of viral RNA and proteins. Previously, we showed that HIV Vpr enhances expression from integrase-defective HIV. Here we show that Vpr activation of expression is partially dependent upon the presence of a transcriptionally active HIV promoter and results in increased transcription of unspliced gag and spliced nef viral RNA. While Tat is detectable during infection with integrase-defective HIV, Tat levels are not affected by the presence of Vpr. Mutation studies reveal that Tat is dispensable for the Vpr-mediated enhancement of expression from unintegrated DNA. We find that virion-associated Vpr is sufficient for Nef expression from unintegrated viral DNA, resulting in the efficient downregulation of CD4 from the surface of infected cells. These results provide a mechanism by which Nef expression from unintegrated HIV type I DNA expression occurs.
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