Abstract
Cellular APOBEC3G (A3G) protein is packaged into human immunodeficiency virus type 1 (HIV-1) virions in producer cells yet restricts viral replication in target cells. To characterize this restriction in target cells, the effect of A3G on generating various HIV-1 cDNA products was measured by quantitative real-time PCR. A3G decreased cDNA products from Vif-deficient HIV-1, with minor effects on early reverse transcripts and larger declines in late reverse transcripts. However, the greatest decline was typically observed in nuclear 2-LTR circles. Moreover, the magnitude of these declines varied with A3G dose. Adding integration inhibitor did not stop the A3G-mediated loss in 2-LTR circles. Moreover, obstructing HIV-1 nuclear entry using vesicular stomatitis virus matrix protein did not stop the A3G-mediated decline in late reverse transcripts. Collectively, these data suggest that A3G has important restriction activity in the cytoplasm and progressively diminishes viral cytoplasmic and nuclear cDNA forms with increasing magnitude during restriction.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1-12 |
| Number of pages | 12 |
| Journal | Virology |
| Volume | 375 |
| Issue number | 1 |
| DOIs | |
| State | Published - May 25 2008 |
Funding
We thank Dr. Michael Malim (King's College London, United Kingdom), Dr. Nathaniel Landau (New York University, New York, USA), and Dr. James Dahlberg plus Dr. Elsebet Lund (University of Wisconsin-Madison, Madison, USA) for generously providing reagents. The integrase inhibitor (118-D-24) and Nevirapine reverse transcription inhibitor were obtained through the NIH AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, and NIH. This work was supported by a National Institutes of Health grant RO1 AI47770 to T.J.H. T.J.H. is an Elizabeth Glaser Scientist.
Keywords
- 2-LTR circles
- APOBEC3G
- Human immunodeficiency virus type 1
- Restriction
- Reverse transcription
ASJC Scopus subject areas
- Virology
