Characterization of Parainfluenza Type 3 and Rs Viruses with Monoclones

Coelingh, K L.

Abstract

We have expanded the operational epitope map and functional map of the type 3 parainfluenza virus (PIV3) hemagglutinin-neuraminidase (HN) protein. Monoclonal antibodies (mAbs) to the HN protein define 14 operationally unique epitopes which are organized into 5 topographically non-overlapping antigenic sites (A, B, D, E, and F) and one bridging site (C). MAbs to sites A, B, and C inhibit hemagglutination and infectivity, and several site A mAbs also inhibit sialidase activity. MAbs to sites D, E, and F do not inhibit any known biological activity and react with all but 1 of 37 clinical PIV3 isolates examined, which is in contrast to mAbs to more variable epitopes in sites A, B, and C. Sequence analysis of HN genes of 16 mAb-resistant antigenic variants indicate the HN epitopes are located in hydrophilic stretches of amino acids. Computer analysis predicts these amino acids to form hydrophilic loops which connect B-sheet structures. Antigenic variants selected with mAbs which cross-react with the bovine PIV3 have amino acid substitutions in residues which are conserved in the primary structures of the parental human and bovine strains. MAbs to the fusion and G surface glycoproteins of respiratory syncytial virus have also been produced and are being characterized prior to selection of antigenic variants, epitope mapping, and sequence analysis of variants.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000327-05
• Application #: 3960549
• Support Year: 5
• Fiscal Year: 1986

Institution

• Name: Niaid Extramural Activities
• Country: United States

Publications

Boonyaratanakornkit, Jim B; Bartlett, Emmalene J; Amaro-Carambot, Emerito et al. (2009) The C proteins of human parainfluenza virus type 1 (HPIV1) control the transcription of a broad array of cellular genes that would otherwise respond to HPIV1 infection. J Virol 83:1892-910

Bartlett, Emmalene J; Hennessey, Margaret; Skiadopoulos, Mario H et al. (2008) Role of interferon in the replication of human parainfluenza virus type 1 wild type and mutant viruses in human ciliated airway epithelium. J Virol 82:8059-70

Bartlett, Emmalene J; Cruz, Ann-Marie; Esker, Janice et al. (2008) Human parainfluenza virus type 1 C proteins are nonessential proteins that inhibit the host interferon and apoptotic responses and are required for efficient replication in nonhuman primates. J Virol 82:8965-77

Bartlett, Emmalene J; Castano, Adam; Surman, Sonja R et al. (2007) Attenuation and efficacy of human parainfluenza virus type 1 (HPIV1) vaccine candidates containing stabilized mutations in the P/C and L genes. Virol J 4:67

Surman, Sonja R; Collins, Peter L; Murphy, Brian R et al. (2007) An improved method for the recovery of recombinant paramyxovirus vaccine candidates suitable for use in human clinical trials. J Virol Methods 141:30-3

Nolan, Sheila M; Skiadopoulos, Mario H; Bradley, Konrad et al. (2007) Recombinant human parainfluenza virus type 2 vaccine candidates containing a 3'genomic promoter mutation and L polymerase mutations are attenuated and protective in non-human primates. Vaccine 25:6409-22

Bartlett, Emmalene J; Amaro-Carambot, Emerito; Surman, Sonja R et al. (2006) Introducing point and deletion mutations into the P/C gene of human parainfluenza virus type 1 (HPIV1) by reverse genetics generates attenuated and efficacious vaccine candidates. Vaccine 24:2674-84

Van Cleve, William; Amaro-Carambot, Emerito; Surman, Sonja R et al. (2006) Attenuating mutations in the P/C gene of human parainfluenza virus type 1 (HPIV1) vaccine candidates abrogate the inhibition of both induction and signaling of type I interferon (IFN) by wild-type HPIV1. Virology 352:61-73

Nolan, Sheila M; Surman, Sonja R; Amaro-Carambot, Emerito et al. (2005) Live-attenuated intranasal parainfluenza virus type 2 vaccine candidates developed by reverse genetics containing L polymerase protein mutations imported from heterologous paramyxoviruses. Vaccine 23:4765-74

Bartlett, Emmalene J; Amaro-Carambot, Emerito; Surman, Sonja R et al. (2005) Human parainfluenza virus type I (HPIV1) vaccine candidates designed by reverse genetics are attenuated and efficacious in African green monkeys. Vaccine 23:4631-46