Regular ArticleThe Kinetics of Human Immunodeficiency Virus Reverse Transcription Are Slower in Primary Human Macrophages Than in a Lymphoid Cell Line
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Vpx requires active cellular dNTP biosynthesis to effectively counteract the anti-lentivirus activity of SAMHD1 in macrophages
2023, Journal of Biological ChemistryViral protein X reduces the incorporation of mutagenic noncanonical rNTPs during lentivirus reverse transcription in macrophages
2020, Journal of Biological ChemistryCitation Excerpt :Unlike infected CD4+ T cells, which undergo rapid cell death, myeloid cells display long-living phenotype following HIV-1 infections (3–5). In addition to that, HIV-1 exhibits more rapid replication kinetics in activated CD4+ T cells compared with that of nondividing myeloid cells (6–8). We have previously reported that the extremely low dNTP concentration found in macrophages (20–40 nm) kinetically restricts HIV-1 reverse transcription, which generally utilizes cellular dNTPs, whereas HIV-1 replicates at higher rate within the higher cellular dNTP pool (1–5 μm) found in activated CD4+ T cells (9).
Mechanistic and kinetic differences between reverse transcriptases of Vpx coding and non-coding lentiviruses
2015, Journal of Biological ChemistryCitation Excerpt :Indeed, we reported that human primary monocyte-derived macrophages have 50–200 times lower dNTP concentrations (20–40 nm) than activated CD4+ T cells (2–4 μm) (7, 8). Importantly, although HIV-1 replication and viral production are robust in activated CD4+ T cells, its replication in non-dividing macrophages is kinetically delayed (9, 10). Our studies demonstrate that the extremely low dNTP level found in macrophages mechanistically contributes to the delayed replication kinetics of HIV-1 in macrophages and non-dividing cells.
Restricted 5′-end gap repair of HIV-1 integration due to limited cellular dNTP concentrations in human primary macrophages
2013, Journal of Biological ChemistryCitation Excerpt :We transduced human primary MDMs with a vesicular stomatitis virus glycoprotein-pseudotyped pD3HIV-GFP vector, which encodes the entire HIV-1 genome except env and nef, which were replaced with enhanced GFP. Because reverse transcription in macrophages reaches completion between 24 and 72 h after initial infection (15, 39, 40), macrophages were initially transduced by HIV-1 vector for 48 h, and further reverse transcription and integration were blocked by treating the cells with 5 μm nevirapine (41) and 1 μm raltegravir, respectively (Fig. 6A). Note that these drugs do not interfere with the 5′-end gap repair machinery (42).