Faculty Collaboration Database

Human anti-varicella-zoster virus (VZV) recombinant monoclonal antibody produced after Zostavax immunization recognizes the gH/gL complex and neutralizes VZV infection. J Virol 2013 Jan;87(1):415-21

Date

10/19/2012

Pubmed ID

23077312

Pubmed Central ID

PMC3536365

DOI

10.1128/JVI.02561-12

Scopus ID

2-s2.0-84872000832 (requires institutional sign-in at Scopus site)   20 Citations

Abstract

Varicella-zoster virus (VZV) is a ubiquitous, highly cell-associated, and exclusively human neurotropic alphaherpesvirus. VZV infection is initiated by membrane fusion, an event dependent in part on VZV glycoproteins gH and gL. Consistent with its location on the virus envelope, the gH/gL complex is a target of neutralizing antibodies produced after virus infection. One week after immunizing a 59-year-old VZV-seropositive man with Zostavax, we sorted his circulating blood plasma blasts and amplified expressed immunoglobulin variable domain sequences by single-cell PCR. Sequence analysis identified two plasma blast clones, one of which was used to construct a recombinant monoclonal antibody (rec-RC IgG). The rec-RC IgG colocalized with VZV gE on the membranes of VZV-infected cells and neutralized VZV infection in tissue culture. Mass spectrometric analysis of proteins immunoprecipitated by rec-RC IgG identified both VZV gH and gL. Transfection experiments showed that rec-RC IgG recognized a VZV gH/gL protein complex but not individual gH or gL proteins. Overall, our recombinant monoclonal anti-VZV antibody effectively neutralizes VZV and recognizes a conformational epitope within the VZV gH/L protein complex. An unlimited supply of this antibody provides the opportunity to analyze membrane fusion events that follow virus attachment and to identify multiple epitopes on VZV-specific proteins.

Author List

Birlea M, Owens GP, Eshleman EM, Ritchie A, Traktinskiy I, Bos N, Seitz S, Azarkh Y, Mahalingam R, Gilden D, Cohrs RJ

Author

Emily M. Eshleman PhD Assistant Professor in the Pediatrics department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Antibodies, Monoclonal
Antibodies, Neutralizing
Antibodies, Viral
Herpes Zoster Vaccine
Herpesvirus 3, Human
Humans
Immunoprecipitation
Male
Membrane Glycoproteins
Middle Aged
Neutralization Tests
Recombinant Proteins
Viral Proteins