Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication

Palamara, Anna Teresa; Perno, Carlo Federico; Ciriolo, Maria Rosa; Dini, Luciana; Balestra, E; D’Agostini, Cartesio; Francesco, Paolo Di; Favalli, Cartesio; Rotilio, Giuseppe; Garaci, Enrico

doi:10.1016/0166-3542(95)00008-a

Cited by 129 publications

(124 citation statements)

References 34 publications

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“…The zinc finger motif of Hsp33 is not found in eukaryotic proteins (70) but is similar to a cysteine motif in the regulatory domain of UL16 (6). Moreover, it is known that HSV infections induce and require oxidative stress for the production of infectious virions (71)(72)(73)(74)(75)(76)(77)(78). But unlike those of Hsp33, the binding activities of the N-terminal portion of UL16 seem to be specific for particular viral proteins: UL11 (6), gE (9), and VP22 (this study).…”

Section: Discussionmentioning

confidence: 99%

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

Starkey

Han

Chadha

et al. 2014

J Virol

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UL16 is a tegument protein of herpes simplex virus (HSV) that is conserved among all members of the Herpesviridae, but its function is poorly understood. Previous studies revealed that UL16 is associated with capsids in the cytoplasm and interacts with the membrane protein UL11, which suggested a "bridging" function during cytoplasmic envelopment, but this conjecture has not been tested. To gain further insight, cells infected with UL16-null mutants were examined by electron microscopy. No defects in the transport of capsids to cytoplasmic membranes were observed, but the wrapping of capsids with membranes was delayed. Moreover, clusters of cytoplasmic capsids were often observed, but only near membranes, where they were wrapped to produce multiple capsids within a single envelope. Normal virion production was restored when UL16 was expressed either by complementing cells or from a novel position in the HSV genome. When the composition of the UL16-null viruses was analyzed, a reduction in the packaging of glycoprotein E (gE) was observed, which was not surprising, since it has been reported that UL16 interacts with this glycoprotein. However, levels of the tegument protein VP22 were also dramatically reduced in virions, even though this gE-binding protein has been shown not to depend on its membrane partner for packaging. Cotransfection experiments revealed that UL16 and VP22 can interact in the absence of other viral proteins. These results extend the UL16 interaction network beyond its previously identified binding partners to include VP22 and provide evidence that UL16 plays an important function at the membrane during virion production. Infectious herpesviruses contain approximately 40 viral proteins and are produced when their DNA-containing capsids are wrapped with a cell-derived membrane in the cytoplasm (1). This envelopment process is driven by complex interactions that are still poorly understood but is known to involve bridging interactions provided by a growing list of tegument proteins, which provide linkages between the capsid and viral membrane proteins (1-3). The UL16 tegument protein of herpes simplex virus (HSV) is remarkable for its numerous interactions with several other viral proteins, namely, tegument protein UL21 (4, 5), membrane protein UL11 (4, 6-8), membrane glycoprotein E (gE) (4, 9), and an unidentified protein(s) that is associated with the capsid (10-12). UL16 is conserved among all the alpha-, beta-, and gammaherpesvirinae (2, 13, 14), but its actual function remains unknown.There are several reasons for suggesting a role for UL16 in HSV envelopment. The earliest study showed that a U L 16-null mutant (here named the ⌬U L 16B mutant) produces infectious virions at a level only one-tenth that of the wild-type virus (15). Also, UL16 has been shown to be bound in some manner to cytoplasmic capsids (10, 16, 17), and thus, its direct interactions with membrane proteins UL11 (8) and gE (9) suggest that UL16 might provide bridging functions that help drive virion production, as first pro...

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Section: Discussionmentioning

confidence: 99%

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

Starkey

Han

Chadha

et al. 2014

J Virol

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“…We hypothesize that the C-terminal regulatory domain of UL16 may also contain a switch that is activated in response to oxidation. In fact, it has been shown that HSV-infected cells undergo oxidative stress (17,21,33,49,56,59,65,70). Hence, it is possible that UL16 utilizes this change to modulate its function.…”

Section: Discussionmentioning

confidence: 99%

Regulated Interaction of Tegument Proteins UL16 and UL11 from Herpes Simplex Virus

Chadha

Han

Starkey

et al. 2012

J Virol

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It is well known that proteins in the tegument (located between the viral capsid and envelope proteins) play critical roles in the assembly and budding of herpesviruses. Tegument proteins UL16 and UL11 of herpes simplex virus (HSV) are conserved among all the Herpesviridae. Although these proteins directly interact in vitro, UL16 was found to colocalize poorly with UL11 in cotransfected cells. To explain this discrepancy, we hypothesized that UL16 is initially made in an inactive form and is artificially transformed to the binding-competent state when cells are disrupted. Consistent with a regulated interaction, UL16 was able to fully colocalize with UL11 when a large C-terminal segment of UL16 was removed, creating mutant UL16 (1-155). Moreover, membrane flotation assays revealed a massive movement of this mutant to the top of sucrose gradients in the presence of UL11, whereas both the full-length UL16 and the C-terminal fragment (residues 156 to 373) remained at the bottom. Further evidence for the presence of a C-terminal regulatory domain was provided by single-amino-acid substitutions at conserved cysteines (C269S, C271S, and C357S), which enabled the efficient interaction of full-length UL16 with UL11. Lastly, the binding site for UL11 was further mapped to residues 81 to 155, and to our surprise, the 5 Cys residues within UL16(1-155) are not required, even though the modification of free cysteines in UL16 with N-ethylmaleimide does in fact prevent binding. Collectively, these results reveal a regulatory function within the C-terminal region of UL16 that controls an N-terminal UL11-binding activity.

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“…An antiviral without interference on cellular metabolism, the glutathione (GSH), was reported by Palamara et al (1995). This is because an antiviral, such as the DLGalactan, extracted from the red seaweed Gymnogongrus torulosus, possesses an action mode of interference on the binding of the surface glycoprotein of the viral envelope to the cell receptor (Pujol et al, 2002).…”

Section: Resultsmentioning

confidence: 99%

“…This activity was obtained by direct contact between the virus and the extract, for 3h before its inoculation in cell culture. An inhibition level of 99.9% on the HSV-1 yield was observed, when the extract from Cordia salicifolian was added in Hela cell monolayers before the virus inoculation, during experiments performed by Palamara et al (1995).…”

Section: Resultsmentioning

confidence: 99%

Inhibition of DNA virus: Herpes-1 (HSV-1) in cellular culture replication, through an antioxidant treatment extracted from rosemary spice

Mancini

Torres

Pinto

et al. 2009

Braz. J. Pharm. Sci.

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This work aimed to evaluate antiviral properties in antioxidants from spices. Phenolic compounds extracted from rosemary (Rosmarinus officinallis, L) by hot water, had their antioxidant activity determined by spectrophotometry using β carotene/linoleic acid system. The rosemary extract was evaluated by antiviral assay of Herpes Virus type-1 (HSV-1) replication in VERO cells, in the presence or absence of the spice. 10,000 TCID 50 /mL of the HSV-1 was kept for 3 h at 4 o C, with 300 ppm of rosemary extract, and 100 ppm of butyl hydroxyl toluene (BHT). Then, these viruses were inoculated in VERO cells incubated at 37 o C in CO 2 -5 %, for seven days. Daily, they were examined and the end point was based on 100% of CPE in virus control (without antioxidants). The HSV-1 replication inhibition percentage (IP) measured the antiviral action from antioxidants, showing viral reductions of the 82.0, 82.5%, in the presence of rosemary and rosemary + BHT, respectively. As an extension, cell test corresponded to the similar viral decrease (IP = 85.0 and 86.3%) in both aforementioned situations. Results lead to conclude that phenolic compounds from rosemary revealed an antiviral action on herpesvirus-1.Uniterms: Natural antioxidants. Virus replication. Phenolic compounds. Herpesvirus. Rosemary.Neste estudo foi avaliada a ação antiviral de antioxidantes de especiaria. Extrato aquoso de alecrim (Rosmarinus officinalis, L), que apresentou atividade antioxidante através de espectrofotometria usando o sistema β caroteno/ácido linoléico, foi avaliado em ensaios com vírus herpes-1 na replicação em células VERO. Nestes ensaios foram utilizados 10.000 TCID 50%/mL do vírus HSV-1, mantidos em contato com 300 ppm do extrato de alecrim e com 100 ppm de butil hidroxi tolueno (BHT), durante 3h a 4°C. Esses vírus, em seguida, foram inoculados em células VERO incubadas a 37 °C/5% de CO 2 por sete dias. Pelo efeito citopático (ECP) e o "end point" de ECP do controle de vírus (sem antioxidante), foi possível observar que houve reduções na replicação viral de 82 e 82,5% na presença do alecrim e do alecrim + BHT, respectivamente. Nessa situação,avaliou-se ainda a redução da adsorção viral às células, que apresentou índices similares de 85,0 e 86,3% de redução na capacidade da adsorção. Estas reduções no desempenho do HSV foram medidas pela fórmula de porcentagem de inibição da replicação viral (PI). Os resultados levam a concluir que os compostos fenólicos do alecrim apresentam ação antiviral sobre o HSV-1.

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Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type 1 replication

Cited by 129 publications

References 34 publications

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

Elucidation of the Block to Herpes Simplex Virus Egress in the Absence of Tegument Protein UL16 Reveals a Novel Interaction with VP22

Regulated Interaction of Tegument Proteins UL16 and UL11 from Herpes Simplex Virus

Inhibition of DNA virus: Herpes-1 (HSV-1) in cellular culture replication, through an antioxidant treatment extracted from rosemary spice

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