A Novel Glycoprotein D-specific Monoclonal Antibody Neutralizes Herpes Simplex Virus

Overview

Journal Antiviral Res

Publisher Elsevier

Date 2017 Oct 25

PMID 29061442

Citations 12

Authors

Ruikun Du

Lili Wang

Hao Xu

Zhiying Wang

Tao Zhang

Manli Wang

Yunjia Ning

Fei Deng

Zhihong Hu

Hualin Wang

Yi Li

Affiliations

Soon will be listed here.

Abstract

The worldwide prevalence of herpes simplex virus (HSV) and the shortage of efficient vaccines and novel therapeutic strategies against HSV are widely global concerns. The abundance on the virion and the major stimulus for the virus-neutralizing antibodies makes gD a predominant candidate for cure of HSV infection. In this study, we generated a monoclonal antibody (mAb), termed m27f, targeting to glycoprotein D (gD) of HSV-2, which also has cross-reactivity against HSV-1 gD. It has a high level of neutralizing activity against both HSV-1 and HSV-2, and binds to a highly conserved region (residues 292-297) within the pro-fusion domain of gD. It can effectively block HSV cell-to-cell spread in vitro. The pre- or post-attachment neutralization assay and syncytium formation inhibition assay revealed that m27f neutralizes HSV at the post-binding stage. Moreover, therapeutic administration of m27f completely prevented infection-related mortality of mice challenged with a lethal dose of HSV-2. Our newly identified epitope for the neutralizing antibody would facilitate studies of gD-based HSV entry or vaccine design, and m27f itself demonstrated a high potential for adaptation as a protective or therapeutic drug against HSV.

Citing Articles

Anti-herpes simplex virus activities and mechanisms of marine derived compounds.

Hao C, Xu Z, Xu C, Yao R Front Cell Infect Microbiol. 2024; 13:1302096.

PMID: 38259968 PMC: 10800978. DOI: 10.3389/fcimb.2023.1302096.

Interactome profiling of Crimean-Congo hemorrhagic fever virus glycoproteins.

Dai S, Min Y, Li Q, Feng K, Jiang Z, Wang Z Nat Commun. 2023; 14(1):7365.

PMID: 37963884 PMC: 10646030. DOI: 10.1038/s41467-023-43206-1.

Inhibition Effects and Mechanisms of Marine Polysaccharide PSSD against Herpes Simplex Virus Type 2.

Yan H, Wang J, Yang J, Xu Z, Li C, Hao C Mar Drugs. 2023; 21(6).

PMID: 37367689 PMC: 10300932. DOI: 10.3390/md21060364.

Antiviral activity and mechanism of the antifungal drug, anidulafungin, suggesting its potential to promote treatment of viral diseases.

Shen S, Zhang Y, Yin Z, Zhu Q, Zhang J, Wang T BMC Med. 2022; 20(1):359.

PMID: 36266654 PMC: 9585728. DOI: 10.1186/s12916-022-02558-z.

Advancing Our Understanding of Corneal Herpes Simplex Virus-1 Immune Evasion Mechanisms and Future Therapeutics.

Greenan E, Gallagher S, Khalil R, Murphy C, Ni Gabhann-Dromgoole J Viruses. 2021; 13(9).

PMID: 34578437 PMC: 8473450. DOI: 10.3390/v13091856.

References

Fusco D, Forghieri C, Campadelli-Fiume G . The pro-fusion domain of herpes simplex virus glycoprotein D (gD) interacts with the gD N terminus and is displaced by soluble forms of viral receptors. Proc Natl Acad Sci U S A. 2005; 102(26):9323-8. PMC: 1166633. DOI: 10.1073/pnas.0503907102. View

Eisenberg R, Atanasiu D, Cairns T, Gallagher J, Krummenacher C, Cohen G . Herpes virus fusion and entry: a story with many characters. Viruses. 2012; 4(5):800-32. PMC: 3386629. DOI: 10.3390/v4050800. View

Shin H, Iwasaki A . Generating protective immunity against genital herpes. Trends Immunol. 2013; 34(10):487-94. PMC: 3819030. DOI: 10.1016/j.it.2013.08.001. View

Navarro D, Paz P, Pereira L . Domains of herpes simplex virus I glycoprotein B that function in virus penetration, cell-to-cell spread, and cell fusion. Virology. 1992; 186(1):99-112. DOI: 10.1016/0042-6822(92)90064-v. View

Evan G, LEWIS G, Ramsay G, Bishop J . Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985; 5(12):3610-6. PMC: 369192. DOI: 10.1128/mcb.5.12.3610-3616.1985. View

Freeman E, Weiss H, Glynn J, Cross P, Whitworth J, Hayes R . Herpes simplex virus 2 infection increases HIV acquisition in men and women: systematic review and meta-analysis of longitudinal studies. AIDS. 2005; 20(1):73-83. DOI: 10.1097/01.aids.0000198081.09337.a7. View

Looker K, Garnett G, Schmid G . An estimate of the global prevalence and incidence of herpes simplex virus type 2 infection. Bull World Health Organ. 2008; 86(10):805-12, A. PMC: 2649511. DOI: 10.2471/blt.07.046128. View

Lawrence Cleary K, Pare E, Stamilio D, Macones G . Type-specific screening for asymptomatic herpes infection in pregnancy: a decision analysis. BJOG. 2005; 112(6):731-6. DOI: 10.1111/j.1471-0528.2005.00540.x. View

Isola V, Eisenberg R, Siebert G, Heilman C, Wilcox W, Cohen G . Fine mapping of antigenic site II of herpes simplex virus glycoprotein D. J Virol. 1989; 63(5):2325-34. PMC: 250651. DOI: 10.1128/JVI.63.5.2325-2334.1989. View

10.

Whitbeck J, Muggeridge M, Rux A, Hou W, Krummenacher C, Lou H . The major neutralizing antigenic site on herpes simplex virus glycoprotein D overlaps a receptor-binding domain. J Virol. 1999; 73(12):9879-90. PMC: 113037. DOI: 10.1128/JVI.73.12.9879-9890.1999. View

11.

Dropulic L, Cohen J . The challenge of developing a herpes simplex virus 2 vaccine. Expert Rev Vaccines. 2012; 11(12):1429-40. PMC: 3593236. DOI: 10.1586/erv.12.129. View

12.

Nicola A, Ponce de Leon M, Xu R, Hou W, Whitbeck J, Krummenacher C . Monoclonal antibodies to distinct sites on herpes simplex virus (HSV) glycoprotein D block HSV binding to HVEM. J Virol. 1998; 72(5):3595-601. PMC: 109580. DOI: 10.1128/JVI.72.5.3595-3601.1998. View

13.

Steiner I, Benninger F . Update on herpes virus infections of the nervous system. Curr Neurol Neurosci Rep. 2013; 13(12):414. DOI: 10.1007/s11910-013-0414-8. View

14.

Looker K, Magaret A, Turner K, Vickerman P, Gottlieb S, Newman L . Global estimates of prevalent and incident herpes simplex virus type 2 infections in 2012. PLoS One. 2015; 10(1):e114989. PMC: 4301914. DOI: 10.1371/journal.pone.0114989. View

15.

Sanna P, De Logu A, Williamson R, Hom Y, Straus S, Bloom F . Protection of nude mice by passive immunization with a type-common human recombinant monoclonal antibody against HSV. Virology. 1996; 215(1):101-6. DOI: 10.1006/viro.1996.0011. View

16.

Zeng F, Hon C, Yip C, Law K, Yeung Y, Chan K . Quantitative comparison of the efficiency of antibodies against S1 and S2 subunit of SARS coronavirus spike protein in virus neutralization and blocking of receptor binding: implications for the functional roles of S2 subunit. FEBS Lett. 2006; 580(24):5612-20. PMC: 7094555. DOI: 10.1016/j.febslet.2006.08.085. View

17.

Cocchi F, Fusco D, Menotti L, Gianni T, Eisenberg R, Cohen G . The soluble ectodomain of herpes simplex virus gD contains a membrane-proximal pro-fusion domain and suffices to mediate virus entry. Proc Natl Acad Sci U S A. 2004; 101(19):7445-50. PMC: 409938. DOI: 10.1073/pnas.0401883101. View

18.

Overall Jr J . Herpes simplex virus infection of the fetus and newborn. Pediatr Ann. 1994; 23(3):131-6. DOI: 10.3928/0090-4481-19940301-06. View

19.

Smith J, Herrero R, Bosetti C, Munoz N, Bosch F, Eluf-Neto J . Herpes simplex virus-2 as a human papillomavirus cofactor in the etiology of invasive cervical cancer. J Natl Cancer Inst. 2002; 94(21):1604-13. DOI: 10.1093/jnci/94.21.1604. View

20.

Wibmer C, Moore P, Morris L . HIV broadly neutralizing antibody targets. Curr Opin HIV AIDS. 2015; 10(3):135-43. PMC: 4437463. DOI: 10.1097/COH.0000000000000153. View