Recombinant Monoclonal Antibody Recognizes a Unique Epitope on Varicella-Zoster Virus Immediate-Early 63 Protein

We previously constructed a recombinant monoclonal antibody (rec-MAb 63P4) that detects immediate-early protein IE63 en-coded by varicella-zoster virus (VZV) in the cytoplasm of productively infected cells. Here, we used ORF63 truncationmutants to map the rec-MAb 63P4 binding epitope to amino acids 141 to 150 of VZV IE63, a region not shared with other widely used anti-IE63 antibodies, and found that the recombinant antibody does not bind to the simian IE63 counterpart. Varicella-zoster virus (VZV) causes childhood varicella (chick-enpox), after which the virus becomes latent in multiple gan-glia along the entire neuraxis. Decades later, as cell-mediated im-munity to VZV declines, VZV can reactivate to cause zoster (shingles) (13). During latency, a number of VZV open reading frames (ORFs) are transcribed (6, 8, 16, 26). Of the VZV ORF transcripts analyzed quantitatively in latently infected human ganglia, ORF63 transcripts are the most prevalent and abundant (7). VZV ORF63 encodes immediate-early 63 (IE63), a 278-ami-no-acid protein expressed early after VZV infection in cell culture (10). Phosphorylated IE63 is found predominantly in the nuclei of productively infected cells (4, 9, 23, 24, 27) but exclusively in th