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

Abstract: 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 (Δ84–85), which was previously unrecoverable, likely due to detrimental effects of the deletion on the P protein. rHPIV1-CΔ84–85+P and an additional mutant, rHPIV1-CΔ169–170+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-CΔ84–85+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-CΔ84–85+P will be investigated as a potential live-attenuated vaccine candidate for HPIV1. [Copyright &y& Elsevier]