APOBEC3G Restricts HIV-1 to a Greater Extent than APOBEC3F and APOBEC3DE in Human Primary CD4 ⁺ T Cells and Macrophages

Abstract

؉ T cells and macrophages, and only the NL4-3 YRHHY>A5 mutant showed a 2-to 4-day delay in replication compared to the wild type. During the subsequent 27 days (round 2) of cultures initiated with peak virus obtained from round 1, the NL4-3 YRHHY>A5 mutant exhibited a longer, 8-to 10-day delay and the NL4-3 DRMR>A4 mutant exhibited a 2-to 6-day delay in replication compared to the wild type. The NL4-3 YRHHY>A5 and NL4-3 DRMR>A4 mutant proviruses displayed G-to-A hypermutations primarily in GG and GA dinucleotides as expected of A3G-and A3F-or A3DE-mediated deamination, respectively. We conclude that A3G exerts a greater restriction effect on HIV-1 than A3F and A3DE.

HIV-1 and HIV-2 Vif Interact with Human APOBEC3 Proteins Using Completely Different Determinants

“…The viruses produced in the presence of either the VPGϾ3A or the WAWϾ3A mutant did not have severely reduced infectivity, strongly suggesting that the levels of A3F and A3H in CEM2n cells are too low to significantly inhibit HIV-1 in a single cycle of replication. These data agree with previously published results from us and other investigators indicating that A3G expression is sufficient to substantially inhibit HIV-1 replication in T cell lines, while A3F does not exert a strong antiviral effect in early infections (41,54) but can inhibit an A3G-specific Vif mutant in multiple cycles of replication (41). However, results from another study suggest that A3F levels in CEM2n cells are sufficient to inhibit HIV-1 replication (53).…”

“…The pFLAG-A3C, -A3D, -A3F, -A3G, -A3H-hapII, -A3H-hapI, -A3G-D128K, -A3F-E289K, -GFG2, and -FGF4 plasmids were previously described (34,(40)(41)(42). Myc-A3A-HA was kindly provided by Gisela Heidecker and David Derse (National Cancer Institute-Frederick).…”

HIV-1 Vpu Accessory Protein Induces Caspase-mediated Cleavage of IRF3 Transcription Factor

“…The plasmids used to prepare virus stocks were: full-length molecular clone pNL4-3 (21) and Vpu-defective (pNL4-3delVpu) (22), Vpr-defective (pNL4-3delVpr) (23), and Vif-defective (pNL4-3delVif) (24) clones. The VSV-G expression vector pHCMV-G (25) was generously provided by Dr. Jane Burns (University of California, San Diego, La Jolla, CA).…”

Identification of a Novel HIV-1 Inhibitor Targeting Vif-dependent Degradation of Human APOBEC3G Protein

“…In addition to A3G, T cells express other APOBEC3 proteins shown to have anti-HIV activity, including A3F and A3C (5,17,41). In contrast to A3G and A3F, APOBEC3C (A3C) exerts only modest antiviral activity against HIV-1 but has potent antiviral activity against simian immunodeficiency virus (66).…”

“…These proteins inhibit not only HIV-1 but also a broad range of other viruses and endogenous retroelements (1)(2)(3)(4). Among the three members of the APOBEC family that exhibit the most potent anti-HIV-1 activity in vivo, APOBEC3D (A3D), ABOBEC3F (A3F), and APOBEC3G (A3G), A3G is the most well characterized and potent HIV-1 inhibitor (5).…”