A novel glycoprotein D-specific monoclonal antibody neutralizes herpes simplex virus

Du, Ruikun; Wang, Lili; Xu, Hao; Wang, Zhiying; Zhang, Tao; Ning, Yun‐Jia; Deng, Fei; Wang, Manli; Li, Yang

doi:10.1016/j.antiviral.2017.10.013

Cited by 18 publications

(11 citation statements)

References 43 publications

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“…In this regard, viral entry can be blocked with antibodies that prevent the interaction between gD and its receptors (Criscuolo et al, 2018 ). For instance, M27f is a monoclonal antibody against gD that has shown neutralizing activity, not only against HSV-1 but also against HSV-2 and that inhibition of the entry process can occur even after attachment of virions to the cell surface (Du et al, 2017 ).…”

Section: Herpes Simplex Virus Entry Into the Host Cellmentioning

confidence: 99%

Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro

et al. 2018

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Herpes simplex viruses type 1 and type 2 (HSV-1 and HSV-2) produce lifelong infections and are highly prevalent in the human population. Both viruses elicit numerous clinical manifestations and produce mild-to-severe diseases that affect the skin, eyes, and brain, among others. Despite the existence of numerous antivirals against HSV, such as acyclovir and acyclovir-related analogs, virus variants that are resistant to these compounds can be isolated from immunosuppressed individuals. For such isolates, second-line drugs can be used, yet they frequently produce adverse side effects. Furthermore, topical antivirals for treating cutaneous HSV infections usually display poor to moderate efficacy. Hence, better or novel anti-HSV antivirals are needed and details on their mechanisms of action would be insightful for improving their efficacy and identifying specific molecular targets. Here, we review and dissect the lytic replication cycles of herpes simplex viruses, discussing key steps involved in cell infection and the processes that yield new virions. Additionally, we review and discuss rapid, easy-to-perform and simple experimental approaches for studying key steps involved in HSV replication to facilitate the identification of the mechanisms of action of anti-HSV compounds.

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Section: Herpes Simplex Virus Entry Into the Host Cellmentioning

confidence: 99%

Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro

et al. 2018

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“…Therefore, further studies on identification of the epitopes, the binding conformation of the five MAbs and even the functional sites of 32 kDa VAP were required to elucidate the neutralization mechanism of the five MAbs. Currently, the binding epitope for herpes simplex virus (HSV) is identified to produce neutralizing antibody, which facilitated studies of HSV entry or vaccine design [ 39 ]. Since the interaction of 32 kDa VAP with the 27.8 kDa receptor was previously confirmed to mediate LCDV attachment and entry [ 16 ], the neutralizing anti-32 kDa VAP MAbs might be promising inhibitors to block the LCDV–receptor binding as an antiviral agent.…”

Section: Discussionmentioning

confidence: 99%

Development and Characterization of Monoclonal Antibodies to the 32 kDa Viral Attachment Protein of Lymphocystis Disease Virus and Their Neutralizing Ability in Vitro

Zhong

Tang

Sheng

et al. 2018

IJMS

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In previous research, a 32 kDa protein in lymphocystis disease virus (LCDV) was identified as viral attachment protein (VAP) that specifically interacted with the 27.8 kDa cellular receptor from flounder Paralichthys olivaceus gill (FG) cells, and the recombinant VAP (rVAP) was expressed in Escherichia coli strain BL21 (DE3). In this study, monoclonal antibodies (MAbs) against 32 kDa VAP are produced by immunization of BALB/c mice with the rVAP. Seven hybridoma secreting MAbs were screened by enzyme-linked immunosorbent assay, five of which designated as 1C6, 1C8, 3B5, 3D11 and 3H10 are cloned by the limiting dilution method, depending on the strongly positive results of ELISA. Western blotting analysis shows that the five MAbs can specifically react with the 32 kDa protein of LCDV and the purified 50 kDa rVAP, and the subtype of the MAbs is identified as IgG. Immunofluorescence results demonstrate that the specific fluorescence signals for LCDV appear in the cytoplasm of FG cells at 24 h post LCDV infection. Neutralization assay results indicate that pre-incubations of LCDV with the five MAbs can significantly decrease the LCDV copy numbers and delay the development of the cytopathic effect in FG cells, revealing that the five MAbs can neutralize the LCDV particles and block viral infection in vitro. The neutralizing MAbs against 32 kDa VAP would be useful for the study on the LCDV–host interaction and might be promising inhibitors of LCDV infection in fish.

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“…Syncytium assays were performed using the method described by Du et al, (), with some modifications. Briefly, monolayers of Vero cells grown in 12‐well plates were infected with HSV‐1 or HSV‐2 (MOI = 3.0) for 2 hr at 4°C.…”

Section: Methodsmentioning

confidence: 99%

Guanidine modifications enhance the anti‐herpes simplex virus activity of (E,E)‐4,6‐bis(styryl)‐pyrimidine derivatives in vitro and in vivo

Wang

Zhang

et al. 2020

British J Pharmacology

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Background and Purpose The worldwide prevalence of herpes simplex virus (HSV) and shortage of efficient therapeutic strategies to counteract it are global concerns. In terms of treatment, the widely utilized anti‐HSV drugs such as acyclovir have serious limitations, for example, drug resistance and side effects. Here, we have identified the guanidine‐modified (E,E)‐4,6‐bis(styryl)‐pyrimidine (BS‐pyrimidine) derivative compound 5d as an inhibitor of HSV and further elucidated the anti‐HSV mechanisms of compound 5d both in vitro and in vivo. Experimental Approach Cytopathic effect inhibition assay, plaque assay, and immunofluorescence assay were used to evaluate the anti‐HSV effects of compound 5d in vitro. Membrane fusion assays, immunofluorescence assays, Western blotting assays, and pull‐down assays were used to explore the anti‐HSV mechanisms of compound 5d. HSV‐1‐infected mice, combined with haematoxylin–eosin staining and quantitative RT‐PCR, were used to study the anti‐HSV effects of compound 5d in vivo. Key Results The guanidine‐modified compound 5d rather than the un‐modified compound 3a effectively inhibited both HSV‐1 and HSV‐2 multiplication in different cell lines, more effectively than acyclovir. Compound 5d may block virus binding and post‐binding processes such as membrane fusion, by targeting virus gB protein. In addition, compound 5d may also down‐regulate the cellular PI3K/Akt signalling pathway to interfere with HSV replication. Treatment with compound 5d also markedly improved survival and decreased viral titres in HSV‐infected mice. Conclusions and Implications Thus, the guanidine‐modified BS‐pyrimidine derivatives have the potential to be developed into novel anti‐HSV agents targeting both virus gB protein and cellular PI3K/Akt signalling pathways.

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A novel glycoprotein D-specific monoclonal antibody neutralizes herpes simplex virus

Cited by 18 publications

References 43 publications

Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro

Experimental Dissection of the Lytic Replication Cycles of Herpes Simplex Viruses in vitro

Development and Characterization of Monoclonal Antibodies to the 32 kDa Viral Attachment Protein of Lymphocystis Disease Virus and Their Neutralizing Ability in Vitro

Guanidine modifications enhance the anti‐herpes simplex virus activity of (E,E)‐4,6‐bis(styryl)‐pyrimidine derivatives in vitro and in vivo

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