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.
Bartlett
Emmalene J
EJ
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.
Cruz
Ann-Marie
AM
Boonyaratanakornkit
Jim
J
Esker
Janice
J
Castaño
Adam
A
Skiadopoulos
Mario H
MH
Collins
Peter L
PL
Murphy
Brian R
BR
Schmidt
Alexander C
AC
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