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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Niederman, T. M. Thielan, B. J. Ratner, L. |
| Description | Author Affiliation: Niederman TM ( Department of Medicine, Washington University School of Medicine, Saint Louis, MO 63110.); |
| Abstract | The negative factor (nef) of human immunodeficiency virus (HIV) type 1 acts to down-regulate virus replication. To decipher the step in the virus life cycle affected by nef, functional proviral clones with (pHIV F-) or without (pHIV F+) a deletion mutation in the nef gene were constructed. In CD4+ cells, 30- to 50-fold more virus was produced over the course of 18-20 days with cultures infected with F- compared to F+ virus. In CD4- cell lines, 2- to 10-fold greater virus production was found from cultures transfected with pHIV F- than those transfected with pHIV F+. The negative regulatory effects of nef on pHIV F- could be supplied in trans with a plasmid expressing only the nef gene product. Virus produced by COS-1 cells transfected with pHIV F- or pHIV F+ showed similar binding, uptake, uncoating, and reverse transcription. Analysis of HIV-1 RNA and structural protein levels and rates of viral RNA synthesis in CD4- cells also showed 2- to 10-fold higher levels in cells transfected with pHIV F- compared to pHIV F+. The activity of a HIV-1-chloramphenicol acetyltransferase (CAT) plasmid was also suppressed by nef, whereas other CAT plasmids were unaffected. These findings demonstrate that nef acts as a specific silencer of HIV-1 transcription. This activity may be critical for maintenance of HIV-1 latency in vivo. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 4 |
| Volume Number | 86 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1989-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | HIV-1 Genetics Retroviridae Proteins Suppression, Genetic Transcription, Genetic Animals Cell Line Gene Products, Nef Genes Genes, Regulator Genes, Viral Growth & Development Kinetics Nucleic Acid Hybridization Transfection Virus Replication Nef Gene Products, Human Immunodeficiency Virus Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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