scholarly journals A versatile platform technology for recombinant vaccines using non-propagative human parainfluenza virus type 2 vector

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Junpei Ohtsuka ◽  
Masayuki Fukumura ◽  
Wakako Furuyama ◽  
Shujie Wang ◽  
Kenichiro Hara ◽  
...  
Keyword(s):  
Virus Type ◽  
Neutralizing Antibodies ◽  
Reverse Genetics ◽  
Ebola Virus ◽  
Vaccine Development ◽  
Virus Production ◽  
Parainfluenza Virus ◽  
Medical Needs ◽  
Human Parainfluenza Virus

Abstract Ectopic protein with proper steric structure was efficiently loaded onto the envelope of the F gene-defective BC-PIV vector derived from human parainfluenza virus type 2 (hPIV2) by a reverse genetics method of recombinant virus production. Further, ectopic antigenic peptide was successfully loaded either outside, inside, or at both sides of the envelope of the vector. The BC-PIV vector harboring the Ebola virus GP gene was able to elicit neutralizing antibodies in mice. In addition, BC-PIV with antigenic epitopes of both melanoma gp100 and WT1 tumor antigen induced a CD8+ T-cell-mediated response in tumor-transplanted syngeneic mice. Considering the low pathogenicity and recurrent infections of parental hPIV2, BC-PIV can be used as a versatile vector with high safety for recombinant vaccine development, addressing unmet medical needs.

scholarly journals The conserved carboxyl terminus of human parainfluenza virus type 2 V protein plays an important role in virus growth

Virology ◽  
2007 ◽  
Vol 362 (1) ◽  
pp. 85-98 ◽  
Author(s):  
Machiko Nishio ◽  
Masato Tsurudome ◽  
Hisamitsu Ishihara ◽  
Morihiro Ito ◽  
Yasuhiko Ito
Keyword(s):  
Virus Type ◽  
Parainfluenza Virus ◽  
Carboxyl Terminus ◽  
Virus Growth ◽  
V Protein ◽  
Human Parainfluenza Virus

scholarly journals Human Parainfluenza Virus Type 2 L Protein Regions Required for Interaction with Other Viral Proteins and mRNA Capping

2010 ◽  
Vol 85 (2) ◽  
pp. 725-732 ◽  
Author(s):  
M. Nishio ◽  
M. Tsurudome ◽  
D. Garcin ◽  
H. Komada ◽  
M. Ito ◽  
...  
Keyword(s):  
Virus Type ◽  
Viral Proteins ◽  
Parainfluenza Virus ◽  
L Protein ◽  
Mrna Capping ◽  
Human Parainfluenza Virus

A point mutation in human parainfluenza virus type 2 nucleoprotein leads to two separate effects on virus replication

2021 ◽  
Author(s):  
Naoki Saka ◽  
Yusuke Matsumoto ◽  
Keisuke Ohta ◽  
Daniel Kolakofsky ◽  
Machiko Nishio
Keyword(s):  
Point Mutation ◽  
Virus Type ◽  
Rna Binding ◽  
Specific Interaction ◽  
Parainfluenza Virus ◽  
Virus Budding ◽  
Virus Life Cycle ◽  
Binding Groove ◽  
Human Parainfluenza Virus

Paramyxovirus genomes, like that of human parainfluenza virus type 2 (hPIV2), are precisely a multiple of six nucleotides long (“rule of six”), in which each nucleoprotein subunit (NP) binds precisely 6 nucleotides. Ten residues of its RNA binding groove contact the genome RNA; but only one, Q202, directly contacts a nucleotide base. Mutation of NP Q202 leads to two phenotypes; the ability of the viral polymerase to replicate minigenomes with defective bipartite promoters where NP wt is inactive, and the inability to rescue rPIV2 carrying this point mutation by standard means. The absence a rPIV2 NP Q202A prevented further study of this latter phenotype. By extensive and repeated co-cultivation of transfected cells, a rPIV2 carrying this mutation was finally recovered, and this virus was apparently viable due to the presence of an additional NP mutation (I35L). Our results suggest that these two phenotypes are due to separate effects of the Q202 mutation, and that of the problematic rescue phenotype may be due to the inability of the transfected cell to incorporate viral nucleocapsids during virus budding. Importance Paramyxovirus genomes are contained within a non-covalent homopolymer of its nucleoprotein (NP) and form helical nucleocapsids (NC) whose 3’ ends contain the promoters for the initiation of viral RNA synthesis. This work suggests that these NC 3’ ends may play another role in the virus life cycle, namely via their specific interaction with virus modified cell membranes needed for the incorporation of viral NCs into budding virions.

scholarly journals Claudin-1 inhibits human parainfluenza virus type 2 dissemination

Virology ◽  
2019 ◽  
Vol 531 ◽  
pp. 93-99 ◽  
Author(s):  
Natsuko Yumine ◽  
Yusuke Matsumoto ◽  
Keisuke Ohta ◽  
Masayoshi Fukasawa ◽  
Machiko Nishio
Keyword(s):  
Virus Type ◽  
Parainfluenza Virus ◽  
Human Parainfluenza Virus

scholarly journals Phosphoprotein of Human Parainfluenza Virus Type 3 Blocks Autophagosome-Lysosome Fusion to Increase Virus Production

2014 ◽  
Vol 15 (5) ◽  
pp. 564-577 ◽  
Author(s):  
Binbin Ding ◽  
Guangyuan Zhang ◽  
Xiaodan Yang ◽  
Shengwei Zhang ◽  
Longyun Chen ◽  
...  
Keyword(s):  
Virus Type ◽  
Virus Production ◽  
Parainfluenza Virus ◽  
Human Parainfluenza Virus ◽  
Type 3

scholarly journals Profilin2 is required for filamentous actin formation induced by human parainfluenza virus type 2

Virology ◽  
2019 ◽  
Vol 533 ◽  
pp. 108-114 ◽  
Author(s):  
Keisuke Ohta ◽  
Yusuke Matsumoto ◽  
Machiko Nishio
Keyword(s):  
Virus Type ◽  
Parainfluenza Virus ◽  
Filamentous Actin ◽  
Human Parainfluenza Virus

scholarly journals Human Parainfluenza Virus Type 2 V Protein Inhibits Genome Replication by Binding to the L Protein: Possible Role in Promoting Viral Fitness

2008 ◽  
Vol 82 (13) ◽  
pp. 6130-6138 ◽  
Author(s):  
Machiko Nishio ◽  
Junpei Ohtsuka ◽  
Masato Tsurudome ◽  
Tetsuya Nosaka ◽  
Daniel Kolakofsky
Keyword(s):  
Virus Type ◽  
Viral Fitness ◽  
Parainfluenza Virus ◽  
Genome Replication ◽  
Gfp Expression ◽  
Virus Growth ◽  
V Protein ◽  
L Protein ◽  
Human Parainfluenza Virus

ABSTRACT The human parainfluenza virus type 2 (hPIV2) V protein plays important roles in inhibiting the host interferon response and promoting virus growth, but its role in hPIV2 replication and transcription is not clear. A green fluorescent protein (GFP)-expressing a negative-sense minigenomic construct of hPIV2 has been established by standard technology, with helper plasmids expressing the nucleocapsid protein (NP), phosphoprotein (P), and large RNA polymerase (L) protein, to examine the role of V protein. We found that the simultaneous expression of wild-type V protein in the minigenome system inhibited GFP expression, at least in part, by inhibiting minigenome replication. In contrast, expression of C terminally truncated or mutant hPIV2 V proteins had no effect. Moreover, the V protein of simian virus 41, the rubulavirus most closely related virus to hPIV2, also inhibited GFP expression, whereas that of PIV5, a more distantly related rubulavirus, did not. Using these other rubulavirus V proteins, as well as various mutant hPIV2 V proteins, we found that the ability of V protein to inhibit GFP expression correlated with its ability to bind to L protein via its C-terminal V protein-specific region, but there was no correlation with NP binding. A possible role for this inhibition of genome replication in promoting viral fitness is discussed.

scholarly journals Generation of Recombinant Human Parainfluenza Virus Type 1 Vaccine Candidates by Importation of Temperature-Sensitive and Attenuating Mutations from Heterologous Paramyxoviruses

2004 ◽  
Vol 78 (4) ◽  
pp. 2017-2028 ◽  
Author(s):  
Jason T. Newman ◽  
Jeffrey M. Riggs ◽  
Sonja R. Surman ◽  
Josephine M. McAuliffe ◽  
Teresa A. Mulaikal ◽  
...  
Keyword(s):  
Respiratory Tract ◽  
Virus Type ◽  
Neutralizing Antibodies ◽  
Effective Means ◽  
Parainfluenza Virus ◽  
Temperature Sensitive ◽  
C Protein ◽  
Vaccine Candidates ◽  
Human Parainfluenza Virus

ABSTRACT Human parainfluenza virus type 1 (HPIV1) is a significant cause of respiratory tract disease in infants and young children for which a vaccine is needed. In the present study, we sought to attenuate HPIV1 by the importation of one or more known attenuating point mutations from heterologous paramyxoviruses into homologous sites in HPIV1. The introduced mutations were derived from three attenuated paramyxoviruses: (i) HPIV3cp45, a live-attenuated HPIV3 vaccine candidate containing multiple attenuating mutations; (ii) the respiratory syncytial virus cpts530 with an attenuating mutation in the L polymerase protein; and (iii) a murine PIV1 (MPIV1) attenuated by a mutation in the accessory C protein. Recombinant HPIV1 (rHPIV1) mutants bearing a single imported mutation in C, any of three different mutations in L, or a pair of mutations in F exhibited a 100-fold or greater reduction in replication in the upper or lower respiratory tract of hamsters. Both temperature-sensitive (ts) (mutations in the L and F proteins) and non-ts (the mutation in the C protein) attenuating mutations were identified. rHPIV1 mutants containing a combination of mutations in L were generated that were more attenuated than viruses bearing the individual mutations, showing that the systematic accretion of mutations can yield progressive increases in attenuation. Hamsters immunized with rHPIV1 mutants bearing one or two mutations developed neutralizing antibodies and were resistant to challenge with wild-type HPIV1. Thus, importation of attenuating mutations from heterologous viruses is an effective means for rapidly identifying mutations that attenuate HPIV1 and for generating live-attenuated HPIV1 vaccine candidates.

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