Abstract
BackgroundHerpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. SCSIO 41501, At present, there are many studies on the anti-tumor, anti-clotting, anti-oxidant and immunoinflammatory effects of Aspergillipeptide D, but little research has been done on the anti-HSV-1 activity of Aspergillipeptide D.MethodsThe anti-HSV-1 activity of Aspergillipeptide D was evaluated by plaque reduction assay. The mechanism of action against HSV-1 was determined from the effective stage. Then we assayed the viral DNA replication, viral RNA synthesis and protein expression, respectively. We also identified the proteins that interact with gB by mass spectrometry, and assayed the effect of Aspergillipeptide D on the interaction between the virus gB protein and cell proteins.ResultsPlaque reduction experiments showed that Aspergillipeptide D did not affect HSV-1 early infection events, including viral inactivation, attachment and penetration. Interestingly, Aspergillipeptide D dramatically reduced both the gene and protein levels of viral late protein gB, and suppressed its location in the endoplasmic reticulum and Golgi apparatus. In contrast, overexpression of gB restored viral production. Finally, proteomic analysis revealed that the numbers of cellular proteins that interacted with gB protein was largely decreased by Aspergillipeptide D. These results suggested that Aspergillipeptide D inhibited gB function to affect HSV-1 intercellular spread.ConclusionsOur results indicated that Aspergillipeptide D might be a potential candidate for HSV-1 therapy, especially for ACV-resistant strains.
Highlights
Chemicals and reagents The cyclic pentapeptide, Aspergillipeptide D, was isolated from the fungal strain Aspergillus SCSIO 41501 [14]
Herpes simplex virus 1 (HSV-1) virus particle consists of a core and a linear double-stranded DNA enclosed in a capsid; an outer envelope containing various glycoproteins covers tegument proteins, which are exterior to the viral capsid [2]
HSV-1/Blue, a TK mutant derived from HSV-1 (KOS) [15], two ACV-resistant clinical HSV-1 strains (HSV-1/106 and HSV-1/153) were a kind gift from Tao Peng (Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences)
Summary
Methods Chemicals and reagents The cyclic pentapeptide, Aspergillipeptide D, was isolated from the fungal strain Aspergillus SCSIO 41501 [14]. Herpes simplex virus 1, an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system. The purpose of this study was to investigate the potency and mechanism of antiviral activity of Aspergillipeptide D, a cyclic pentapeptide isolated from a culture broth of marine gorgonian-derived fungus Aspergillus sp. Herpes simplex virus 1 (HSV-1), an enveloped DNA virus belonging to the Herpesviridae family, spreads to neurons and causes pathological changes in the central nervous system [1]. HSV-1 virus particle consists of a core and a linear double-stranded DNA enclosed in a capsid; an outer envelope containing various glycoproteins covers tegument proteins, which are exterior to the viral capsid [2]. The development of novel anti-HSV agents with different mechanisms of action is urgent
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