Abstract
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.
Highlights
A protein exhibiting more than one biochemical function is termed a moonlighting protein
ENO1 in HIV‐1 target cells influences viral infectivity We previously reported that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and ENO1 are incorporated into human immunodeficiency virus type 1 (HIV-1) particles, and virion-incorporated GAPDH and ENO1 inhibit viral reverse transcription independently of each other [24, 26]
In this study, we examined whether GAPDH and ENO1 expression levels were changed by HIV-1 infection
Summary
A protein exhibiting more than one biochemical function is termed a moonlighting protein. 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. It remains unclear whether these proteins expressed in viral target cells affect the early phase of HIV-1 replication. ENO1, which was initially identified as a glycolytic enzyme that catalyzes the conversion of 2-phosphoglycerate to phosphoenolpyruvate in glycolysis, is a moonlighting protein functioning as a plasminogen receptor, a heat-shock protein and a hypoxic stress protein, and associates with infectious viruses such as the Sendai and dengue viruses [22, 23] These studies raised the question of whether glycolytic enzymes can regulate HIV-1 replication as moonlighting proteins. The effects of the moonlighting functions of GAPDH and ENO1 on HIV-1 target cells have not been clarified
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