Laboratory Studies of Parainfluenza Type 3 Virus

Hall, S L.

Abstract

The JS strain of PIV3 is the wild type parent of three candidate live attenuated cold-passaged (cp) viruses; namely cp12, cp18, and cp45. In order to develop an understanding of the genetic basis of attenuation of the mutant viruses, the nucleotide and deduced amino acid sequence of the JS wt and cp12 and cp45 mutant viruses was undertaken. The complete sequence of the JS wild type PIV3 has been obtained and that of the cp12 and cp45 mutants is almost completed. The most promising attenuated vaccine candidate, the cp45 virus, contains at least 16 nucleotide changes from the JS wild type virus (a few nucleotide differences remain to be confirmed). We are using the cDNA clones employed to sequence the JS wild type and cp45 viruses to construct complete cDNA copies of each of these two viruses, a project that is 70% complete. A strategy is being developed to produce an infectious virus from RNA transcribed from the complete copy of PIV3 which will greatly accelerate our ability to produce live attenuated PIV3 vaccines.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Intramural Research (Z01)
• Project #: 1Z01AI000327-11
• Application #: 3790726
• Support Year: 11
• Fiscal Year: 1992

Institution

• Name: National Institute of Allergy and Infectious Diseases
• 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

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; 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

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