GB Virus Type C E2 Protein Inhibits Human Immunodeficiency Virus Type 1 Assembly Through Interference With HIV-1 Gag Plasma Membrane Targeting

Timmons, Christine L.; Shao, Qiujia; Wang, Chenliang; Liu, Ling; Liu, Huanliang; Dong, Xinhong; Liu, Bindong

doi:10.1093/infdis/jit001

Cited by 14 publications

(23 citation statements)

References 50 publications

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“…In another study, patients co‐infected with GBV‐C genotype 2 had higher T‐helper CD4+ cell counts compared to those with genotype 1 [Schwarze‐Zander et al, ]. One possible mechanism underlying this phenomenon may be the interference of the GBV‐C envelope glycoprotein E2 with HIV‐1 cell entry [Xiang et al, ; Timmons et al, ]. Other GBV‐C peptide domains, such as the non‐structural 5A (NS5A) phosphoprotein and non‐structural 3‐serine protease, have also been reported to inhibit HIV‐1 replication [Xiang et al, ; George et al, ].…”

Section: Introductionmentioning

confidence: 99%

Epidemiology of GB virus type C among patients infected with HIV in Singapore

Lee

Tang

Chiu

et al. 2014

Journal of Medical Virology

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Several studies have shown that individuals co-infected with GB virus type C (GBV-C), and human immunodeficiency virus (HIV) have slower progression to acquired immunodeficiency syndrome (AIDS) and a prolonged lifespan, compared to those infected with only HIV. In Singapore, despite the steadily increasing number of HIV infections in recent years, there are no studies documenting the extent of GBV-C/HIV co-infection in this group of patients. To fill this dearth of information, two GBV-C screening assays was performed on 80 archived HIV-1-positive samples from the National University Hospital. The overall prevalence of GBV-C co-infection among patients infected with HIV in this study was 10% (8/80). Phylogenetic analysis of the eight dual-infection cases revealed that genotypes 3 (4/8, 50%) and 2a (2/8, 25%) were the main genotypes circulating among these Singaporean HIV patients. One case each of genotypes 2b (1/8, 12.5%) and 4 (1/8, 12.5%), which have not been described previously in Singapore, were identified. These findings hint at the complex epidemiology of GBV-C in different patient groups and a larger study would be needed to characterize, and understand the potential clinical impact of GBV-C co-infection on the patients.

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Section: Introductionmentioning

confidence: 99%

Epidemiology of GB virus type C among patients infected with HIV in Singapore

Lee

Tang

Chiu

et al. 2014

Journal of Medical Virology

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“…Thus, the secretory signal peptide of immunoglobulin G (IgG) was fused to the N-terminus of E2 to create a glycosylated E2 expression construct (IgG-E2). We previously showed that the GBV-C envelope glycoprotein E2 (IgG-E2) could inhibit HIV-1 assembly and release by disrupting the targeting of HIV-1 Gag to the plasma membrane [ 17 ]. As the ARF proteins were reported to facilitate Gag-membrane binding [ 26 ], we decided to examine whether the E2 expression has an effect on ARF proteins and mRNA levels.…”

Section: Resultsmentioning

confidence: 99%

“…Since ARF1 is the most abundant, active and best-characterized ARF family protein [reviewed in [ 24 ]], we will focus on studying the interplay between IgG-E2 and ARF1 in this study. The unglycosylated E2 and E2DMID, which had no effect on HIV-1 assembly and release in our prior study [ 17 ], were used as a control in this study. Both IgG-E2 and E2DMID contain an IgG signal peptide at the N-terminus, and the only difference between them is the internal deletion of the membrane interaction domain (MID) region of IgG-E2 in the E2DMID construct.…”

Section: Resultsmentioning

confidence: 99%

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GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1

et al. 2015

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GB virus type C (GBV-C) glycoprotein E2 protein disrupts HIV-1 assembly and release by inhibiting Gag plasma membrane targeting, however the mechanism by which the GBV-C E2 inhibits Gag trafficking remains unclear. In the present study, we identified ADP-ribosylation factor 1 (ARF1) contributed to the inhibitory effect of GBV-C E2 on HIV-1 Gag membrane targeting. Expression of GBV-C E2 decreased ARF1 expression in a proteasomal degradation-dependent manner. The restoration of ARF1 expression rescued the HIV-1 Gag processing and membrane targeting defect imposed by GBV-C E2. In addition, GBV-C E2 expression also altered Golgi morphology and suppressed protein traffic through the secretory pathway, which are all consistent with a phenotype of disrupting the function of ARF1 protein. Thus, our results indicate that GBV-C E2 inhibits HIV-1 assembly and release by decreasing ARF1, and may provide insights regarding GBV-C E2's potential for a new therapeutic approach for treating HIV-1.

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“…After treatment, cells were analyzed by either qRT-PCR or Western-blot as described previously [43].…”

Section: Methodsmentioning

confidence: 99%

Heat-Stable Molecule Derived from Streptococcus cristatus Induces APOBEC3 Expression and Inhibits HIV-1 Replication

et al. 2014

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Although most human immunodeficiency virus type 1 (HIV-1) cases worldwide are transmitted through mucosal surfaces, transmission through the oral mucosal surface is a rare event. More than 700 bacterial species have been detected in the oral cavity. Despite great efforts to discover oral inhibitors of HIV, little information is available concerning the anti-HIV activity of oral bacterial components. Here we show that a molecule from an oral commensal bacterium, Streptococcus cristatus CC5A can induce expression of APOBEC3G (A3G) and APOBEC3F (A3F) and inhibit HIV-1 replication in THP-1 cells. We show by qRT-PCR that expression levels of A3G and A3F increase in a dose-dependent manner in the presence of a CC5A extract, as does A3G protein levels by Western blot assay. In addition, when the human monocytic cell line THP-1 was treated with CC5A extract, the replication of HIV-1 IIIB was significantly suppressed compared with IIIB replication in untreated THP-1 cells. Knock down of A3G expression in THP-1 cells compromised the ability of CC5A to inhibit HIV-1 IIIB infectivity. Furthermore, SupT1 cells infected with virus produced from CC5A extract-treated THP-1 cells replicated virus with a higher G to A hypermutation rate (a known consequence of A3G activity) than virus used from untreated THP-1 cells. This suggests that S. cristatus CC5A contains a molecule that induces A3G/F expression and thereby inhibits HIV replication. These findings might lead to the discovery of a novel anti-HIV/AIDS therapeutic.

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GB Virus Type C E2 Protein Inhibits Human Immunodeficiency Virus Type 1 Assembly Through Interference With HIV-1 Gag Plasma Membrane Targeting

Cited by 14 publications

References 50 publications

Epidemiology of GB virus type C among patients infected with HIV in Singapore

Epidemiology of GB virus type C among patients infected with HIV in Singapore

GB virus type C E2 protein inhibits human immunodeficiency virus type 1 Gag assembly by downregulating human ADP-ribosylation factor 1

Heat-Stable Molecule Derived from Streptococcus cristatus Induces APOBEC3 Expression and Inhibits HIV-1 Replication

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