Use of monoclonal antibodies to identify four neutralization immunogens on a common cold picornavirus, human rhinovirus 14

Abstract

A collection of 35 mouse monoclonal antibodies, raised against human rhinovirus 14 (HRV-14), was used to isolate 62 neutralization-resistant mutants. When cross-tested against the antibodies in a neutralization assay, the mutants fell into four antigenic groups, here called neutralization immunogens: NIm-IA,-IB,-II, and-III. Sequencing the mutant RNA in segments corresponding to serotype-variable regions revealed that the amino acid substitutions segregated into clusters, which correlated exactly with the immunogenic groups (NIm-IA mutants at VP1 amino acid residue 91 or 95; NIm-Il mutants at VP2 residue 158, 159, 161, or 162; NIm-Ill mutants at VP3 residue 72, 75, or 78; and NIm-IB mutants at two sites, either VP1 residue 83 or 85, or residue 138 or 139). Examination of the three-dimensional structure of the virus (M.

A Novel Universal Neutralizing Monoclonal Antibody against Enterovirus 71 That Targets the Highly Conserved “Knob” Region of VP3 Protein

“…Hence, we have discovered an additional conformational epitope of EV71, and provided the first evidence of another capsid protein involved in EV71 virus neutralization besides VP1. The knob of EV71 VP3 encompasses residues 55 to 69 of VP3making it longer than the knob described for coxsackievirus B3 (CVB3) -and contains a major neutralization site for other picornaviruses such as CVB3, poliovirus 1, human rhinovirus 14 and hepatitis A virus [41][42][43][44]. In hepatitis A virus the immunodominant epitope involves residue 70 of VP3 which is close to the mutations identified in our screen [44].…”

Escape from Human Monoclonal Antibody Neutralization Affects In Vitro and In Vivo Fitness of Severe Acute Respiratory Syndrome Coronavirus

“…antigenic sites for several viruses, including rhinovirus and SARS-CoV [17][18][19][20][21], and it previously has been used to identify the importance of P462 in the neutralization of SARS-CoV by MAb CR3014 [21]. The structures of 2 MAbs complexed with the SARS-CoV RBD have been described elsewhere [15,16].…”

Distinctive features of foot-and-mouth disease virus, a member of the picornavirus family; aspects of virus protein synthesis, protein processing and structure

“…Sequence analysis of such mutants has identified distinct clusters of residues within each antigenic site which are considered to lie within the contact area of the antibodies on the virus. Work on PV (reviewed in Minor, 1990), HRV14 (Sherry et al, 1986) and FMDV (Xie et al, 1987;Thomas et al, 1988;Kitson et al, 1990) have identified 3--4 distinct antigenic sites in each virus. The location of the residues identified by sequence analysis of Mab escape mutants of type O1K FMDV (Xie et al, 1987;Kitson et al, 1990) have been mapped onto the 3D structure of the virus as determined by X-ray crystallography and they are shown in Fig.…”