Virion-incorporated alpha-enolase suppresses the early stage of HIV-1 reverse transcription

Iga, Nozomi; Yamamoto, Kengo; Takamune, Nobutoki; Misumi, Shogo

doi:10.1016/j.bbrc.2017.01.096

Cited by 19 publications

(45 citation statements)

References 20 publications

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“…5A, lane 3, the high-level-ENO1-packaging virus showed signi cant decreases in its infectivity in normal TZM-bl cells. This nding is consistent with our previous ndings [26]. Furthermore, as shown in Fig.…”

Section: Eno1 Has Bifunctional Inhibitory Activities On Hiv-1 Infectionsupporting

confidence: 94%

“…3F). Previously, we reported that high-level-ENO1-packaging virus, which was prepared by cotransfection of HEK293 cells with pNL-CH and ENO1-V5 expression vector, showed decreased number of copies of viral reverse transcription products [26]. Therefore, on the basis of these ndings, we hypothesized that ENO1 is a bifunctional inhibitory protein that inhibits reverse transcription and integration processes.…”

Section: Eno1 Overexpression In Hiv-1 Target Cells Decreases Viral Inmentioning

confidence: 95%

“…We previously reported that GAPDH and ENO1 are incorporated into HIV-1 particles, and virionincorporated GAPDH and ENO1 inhibit viral reverse transcription independently of each other [24,26]. Therefore, in this study, we examined whether GAPDH and ENO1 expression levels were changed by HIV-1 infection.…”

Section: Eno1 In Hiv-1 Target Cells In Uences Viral Infectivitymentioning

confidence: 96%

“…2B). We next investigated whether ENO1 knockdown in TZM-bl cells enhances the viral reverse transcription because low-level-ENO1-packaging virus, which was prepared by transfection of CEM/LAV-1 cells with an ENO1-speci c siRNA, showed an increased reverse transcription e ciency [26]. Unexpectedly, ENO1 knockdown has no effect on the abundance of late R/gag products of reverse transcription (Fig.…”

Section: Eno1 Knockdown In Hiv-1 Target Cells Increases Viral Integramentioning

confidence: 99%

“…We previously demonstrated that GAPDH binds to HIV-1 precursor proteins and is incorporated into virions to prevent the incorporation of the tRNA Lys3 complex and inhibits the initiation of HIV-1 reverse transcription [24,25]. Moreover, we found that packaging of ENO1 into viral particles affects the early stage of viral reverse transcription [26]. However, the effects of the moonlighting functions of GAPDH and ENO1 on HIV-1 target cells have not been clari ed.…”

Section: Introductionmentioning

confidence: 99%

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Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration.

Kishimoto

Yamamoto

Iga

et al. 2020

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BackgroundA protein exhibiting more than one biochemical function is termed a moonlighting protein. Glycolytic enzymes are typical moonlighting proteins, and these enzymes control the infection of various viruses. Previously, we reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and alpha-enolase (ENO1) are incorporated into human immunodeficiency virus type 1 (HIV-1) particles from viral producer cells and suppress viral reverse transcription independently each other. However, it remains unclear whether these proteins expressed in viral target cells affect the early phase of HIV-1 replication.ResultsHere we show that the GAPDH expression level in viral target cells does not affect the early phase of HIV-1 replication, but ENO1 has a capacity to suppress viral integration in viral target cells. In contrast to GAPDH, suppression of ENO1 expression by RNA interference in the target cells increased viral infectivity, but had no effect on the expression levels of the HIV-1 receptors CD4, CCR5 and CXCR4 and on the level of HIV-1 entry. Quantitative analysis of HIV-1 reverse transcription products showed that the number of copies of the late products (R/ gag ) and two-long-terminal-repeat circular forms of viral cDNAs did not change but that of the integrated (Alu- gag ) form increased. In contrast, overexpression of ENO1 in viral target cells decreased viral infectivity owing to the low viral integration efficiency. Results of subcellular fractionation experiments suggest that the HIV integration at the nucleus was negatively regulated by ENO1 localized in the nucleus. In addition, the overexpression of ENO1 in both viral producer cells and target cells most markedly suppressed the viral replication.ConclusionsThese results indicate that ENO1 in the viral target cells prevents HIV-1 integration. Importantly, ENO1, but not GAPDH, has the bifunctional inhibitory activity against HIV-1 replication. The results provide and new insights into the function of ENO1 as a moonlighting protein in HIV-1 infection.

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Section: Eno1 Has Bifunctional Inhibitory Activities On Hiv-1 Infectionsupporting

confidence: 94%

Section: Eno1 Overexpression In Hiv-1 Target Cells Decreases Viral Inmentioning

confidence: 95%

Section: Eno1 In Hiv-1 Target Cells In Uences Viral Infectivitymentioning

confidence: 96%

Section: Eno1 Knockdown In Hiv-1 Target Cells Increases Viral Integramentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration.

Kishimoto

Yamamoto

Iga

et al. 2020

Preprint

Self Cite

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Non-metabolic role of alpha-enolase in virus replication

et al. 2022

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Biological Aging in People Living with HIV on Successful Antiretroviral Therapy: Do They Age Faster?

Akusjärvi

Neogi

2023

Curr HIV/AIDS Rep

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Purpose of Review In the absence of a prophylactic/therapeutic vaccine or cure, the most amazing achievement in the battle against HIV was the discovery of effective, well-tolerated combination antiretroviral therapy (cART). The primary research question remains whether PLWH on prolonged successful therapy has accelerated, premature, or accentuated biological aging. In this review, we discuss the current understanding of the immunometabolic profile in PLWH, potentially associated with biological aging, and a better understanding of the mechanisms and temporal dynamics of biological aging in PLWH. Recent Findings Biological aging, defined by the epigenetic alterations analyzed by the DNA methylation pattern, has been reported in PLWH with cART that points towards epigenetic age acceleration. Summary The hastened development of specific clinical geriatric syndromes like cardiovascular diseases, metabolic syndrome, cancers, liver diseases, neurocognitive diseases, persistent low-grade inflammation, and a shift toward glutamate metabolism in PLWH may potentiate a metabolic profile at-risk for accelerated aging.

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Virion-incorporated alpha-enolase suppresses the early stage of HIV-1 reverse transcription

Cited by 19 publications

References 20 publications

Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration.

Alpha-enolase in viral target cells suppresses the human immunodeficiency virus type 1 integration.

Non-metabolic role of alpha-enolase in virus replication

Biological Aging in People Living with HIV on Successful Antiretroviral Therapy: Do They Age Faster?

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