RÉSUMÉ
Apolipoprotein B mRNA editing enzyme-catalytic polypeptidelike 3G (APOBEC3G), which belongs to the APOBEC family, restricts the replication of HIV-1 through the deminase-dependent and deminase-independent antiviral mechanisms. Viral infectivity factor (Vif), an accessory protein edited by vif gene of HIV-1, promotes APOBEC3G ubiquitination and subsequent degradation by the proteasome result ing in the increased replication of HIV-1. Over the past few years, the discovery of some co-factors such as CBF-β, HDAC6 and MDM2 not only raises our awareness of the interaction between APOBEC3G and Vif but also provides new antiviral targets of HIV-1 in addition. Here we review the structure of APOBEC3G and Vif, and the effect of interference agents on HIV-1 replication by interacting with APOBEC3G and Vif.
RÉSUMÉ
Human APOBEC3G (hA3G) is a cytidine deaminase which inhibits HIV-1 replication. The HIV-1 accessory protein viral infectivity factor (Vif) counteracts with hA3G by targeting it for proteasomal degradation. In this work, we constructed and optimized molecular models of the hA3G dimer and the hA3G-Vif complex. The molecular modeling study revealed that the loop7 motif of hA3G appears on the interfaces of both the hA3G-Vif complex and the hA3G dimer. Biochemical analysis provided evidence suggesting that binding of Vif to hA3G results in steric blocking of hA3G dimerization, implying that monomeric hA3G serves as a substrate for Vif-mediated degradation. Furthermore, we presented evidence for the important roles of the loop7 motif, especially the central residues within the region, in hA3G dimerization, hA3G--Vif interaction, Vif-mediated hA3G degradation as well as subcellular localization of hA3G. This work highlights a multiple-task interface formed by loop7 motif, which regulates biological function of hA3G, thus providing the feasibility of the strategy of blocking Vif-mediated A3G degradation by targeting the putative site around loop7.
RÉSUMÉ
Objective To study the mRNA expression of apolipoprotein B mRNA-editing enzyme-catalytic polypeptide-like 3G (APOBEC3G) in the peripheral blood mononuclear cells (PBMC) in patients with chronic hepatitis C (CHC) and its regulation by exogenous interferon-α (IFN-α).Methods Twenty-eight CHC patients were recruited as case group and 14 healthy subjects were recruited as control group.APOBEC3G mRNA level (the ratio of APOBEC3G mRNA to housekeep geue 18s rRNA) in PBMC was determined by TaqMan real-time polymerase chain reaction (RTPCR).APOBEC3G mRNA levels were also dynamically measured in CHC patients treated with pegylated interferon (IFN)-α 2a at week 0,2,4,12,24,36 and 48 of treatment,and the plasma levels of IFN-α were simultaneously detected by enzyme-linked immunosorbent assay (ELISA).The data were analyzed by t test and analysis of variance using SPSS 11.0 software.Results The level of APOBEC3G mRNA in PBMC of CHC patients before treatment was 1.60× 10-4 ± 1.35 × 10-4,which was significantly lower than healthy controls 6.20 × 10-4 ±1.30 × 10-4 (t=3.147,P=0.003).The expressions of APOBEC3G mRNA were upregulated at week 12,24,36 and 48 of IFN treatment,which were 5.69×10-3±1.61×10-2,1.01×10-2±2.15×10-2,2.01×10-2±3.75×10-2 and 2.45× 10-2 ±4.08× 10-2,respectively,and all higher than that of pretreatment (F=3.46,5.67,10.27 and 25.65,respectively; P=0.042,0.030,0.010 and 0,respectively).IFN-α level in plasma were increased with treatment and reached the plateau at week 2 of the treatment until the end of observation.Conclusion Hepatitis C virus infection may be one of the reasons of APOBEC3G downregulation.
RÉSUMÉ
In recent years, new targets research of Anti-HIV drugs brings in new hope for the development of Anti-HIV drags. Based on Science Citation Index Expanded, the paper analyzes the research focus, country distribution and research institution distribution of new targets of anti-HIV drugs by Bibliometrics.
RÉSUMÉ
Interaction between the HIV-1 Vif protein and the cellular host APOBEC3G protein is a promising target for inhibition of HIV-1 replication. Considering that human cells are a very complicated environment for the study of protein interactions, the goal of this study was to check whether fission yeast could be used as a model cell for studying the Vif-APOBEC3G interaction. Vif and APOBEC3G were expressed in fusion with GFP protein in the S. pombe SP223 strain. Subcellular localizations of Vif and APOBEC3G were observed with fluorescent microscopy. Codon optimization was used to over express the Vif protein in S. pombe cells. The degradation of APOBEC3G mediated by Vif was tested through expressing Vif and GFP-APOBEC3G proteins in the same cell. Western Blot analysis was used to measure the corresponding protein levels under different experimental conditions. The results showed that the Vif protein was predominantly localized in the nucleus of S.pombe cells, APOBEC3G was localized in the cytoplasm and concentrated at punctate bodies that were often in close proximity to the nucleus but were not necessarily restricted from other regions in the cytoplasm. Vif protein expression levels were increased significantly by using codon optimization and APOBEC3G was degraded when Vif was over-expressed in the same S. pombe cells. These results indicate that fission yeast is a good model for studying the interaction between the Vif and APOBEC3G proteins.