A novel human parainfluenza virus type 1 (HPIV1) with separated P and C genes is useful for generating C gene mutants for evaluation as live-attenuated virus vaccine candidates.
A novel recombinant human parainfluenza virus type 1 (rHPIV1), rHPIV1-C+P, in which the overlapping open reading frames of the C and P genes were separated in order to introduce mutations into the C gene without affecting P, was generated. Infectious rHPIV1-C+P was readily recovered and replicated as efficiently as HPIV1 wild type (wt) in vitro and in African green monkeys (AGMs). rHPIV1-C+P expressed increased levels of C protein and, surprisingly, activated the type I IFN and apoptosis responses more strongly than HPIV1 wt. rHPIV1-C+P provided a useful backbone for recovering an attenuated P/C gene mutation (Delta 84-85), which was previously unrecoverable, likely due to detrimental effects of the deletion on the P protein. rHPIV1-C(Delta 84-85)+P and an additional mutant, rHPIV1-C(Delta 169-170)+P, were found to replicate to similar titers in vitro and to activate the type I IFN and apoptosis responses to a similar degree as rHPIV1-C+P. rHPIV1-C(Delta 84-85)+P was found to be highly attenuated in AGMs, and all viruses were immunogenic and effective in protecting AGMs against challenge with HPIV1 wt. rHPIV1-C(Delta 84-85)+P will be investigated as a potential live-attenuated vaccine candidate for HPIV1.
Laboratory of Infectious Diseases, RNA Viruses Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, MD 20892-2007, USA.
Emmalene J
EJ
Bartlett
Ann-Marie
AM
Cruz
Jim
J
Boonyaratanakornkit
Janice
J
Esker
Adam
A
Castaño
Mario H
MH
Skiadopoulos
Peter L
PL
Collins
Brian R
BR
Murphy
Alexander C
AC
Schmidt
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D017209:Apoptosis; D001483:Base Sequence; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D007370:Interferon Type I / Q000096:biosynthesis; D008969:Molecular Sequence Data; D022241:Parainfluenza Vaccines / Q000235:genetics / Q000276:immunology*; D010222:Parainfluenza Virus 1, Human / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity*; D010750:Phosphoproteins / Q000235:genetics*; D017384:Sequence Deletion; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D014764:Viral Proteins / Q000235:genetics*; D014774:Virulence; D014779:Virus Replication
D000914:Antibodies, Viral; D007370:Interferon Type I; D022241:Parainfluenza Vaccines; D010750:Phosphoproteins; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D014764:Viral Proteins; C068855:P protein, parainfluenza virus 1; C068856:C protein, human parainfluenza virus type 1