scholarly journals Chimeric Bovine Respiratory Syncytial Virus with Attachment and Fusion Glycoproteins Replaced by Bovine Parainfluenza Virus Type 3 Hemagglutinin-Neuraminidase and Fusion Proteins

2001 ◽  
Vol 75 (19) ◽  
pp. 9367-9377 ◽  
Author(s):  
Matthias B. Stope ◽  
Axel Karger ◽  
Ulrike Schmidt ◽  
Ursula J. Buchholz
Keyword(s):  
Virus Type ◽  
Open Reading Frames ◽  
Open Reading Frame ◽  
Chimeric Virus ◽  
Parainfluenza Virus ◽  
Confocal Laser ◽  
Reading Frame ◽  
Syncytial Virus ◽  
Type 3 ◽  
Bovine Parainfluenza Virus

ABSTRACT Chimeric bovine respiratory syncytial viruses (BRSV) expressing glycoproteins of bovine parainfluenza virus type 3 (BPIV-3) instead of BRSV glycoproteins were generated from cDNA. In the BRSV antigenome cDNA, the open reading frames of the major BRSV glycoproteins, attachment protein G and fusion protein F, were replaced individually or together by those of the BPIV-3 hemagglutinin-neuraminidase (HN) and/or fusion (F) glycoproteins. Recombinant virus could not be recovered from cDNA when the BRSV F open reading frame was replaced by the BPIV-3 F open reading frame. However, cDNA recovery of the chimeric virus rBRSV-HNF, with both glycoproteins replaced simultaneously, and of the chimeric virus rBRSV-HN, with the BRSV G protein replaced by BPIV-3 HN, was successful. The replication rates of both chimeras were similar to that of standard rBRSV. Moreover, rBRSV-HNF was neutralized by antibodies specific for BPIV-3, but not by antibodies specific to BRSV, demonstrating that the BRSV glycoproteins can be functionally replaced by BPIV-3 glycoproteins. In contrast, rBRSV-HN was neutralized by BRSV-specific antisera, but not by BPIV-3 specific sera, showing that infection of rBRSV-HN is mediated by BRSV F. Hemadsorption of cells infected with rBRSV-HNF and rBRSV-HN proved that BPIV-3 HN protein expressed by rBRSV is functional. Colocalization of the BPIV-3 glycoproteins with BRSV M protein was demonstrated by confocal laser scan microscopy. Moreover, protein analysis revealed that the BPIV-3 glycoproteins were present in chimeric virions. Taken together, these data indicate that the heterologous glycoproteins were not only expressed but were incorporated into the envelope of recombinant BRSV. Thus, the envelope glycoproteins derived from a member of theRespirovirus genus can together functionally replace their homologs in a Pneumovirus background.

scholarly journals Development and validation of a bovine parainfluenza virus type 3 indirect ELISA

2021 ◽  
Vol 6 (6) ◽  
pp. 196-205
Author(s):  
Silvina Soledad Maidana ◽  
Maria Mercedes Odeon ◽  
Carola Maria Ferrecio ◽  
Noelia Magali Grazziotto ◽  
Eddie Pisano ◽  
...  
Keyword(s):  
Virus Type ◽  
Indirect Elisa ◽  
Parainfluenza Virus ◽  
Development And Validation ◽  
Type 3 ◽  
Bovine Parainfluenza Virus

scholarly journals A Prototype Recombinant Vaccine Against Respiratory Syncytial Virus and Parainfluenza Virus Type 3

1994 ◽  
Vol 12 (8) ◽  
pp. 813-818 ◽  
Author(s):  
Run-Pan Du ◽  
Gail E. D. Jackson ◽  
Philip R. Wyde ◽  
Wei-Yao Yan ◽  
Qijun Wang ◽  
...  
Keyword(s):  
Respiratory Syncytial Virus ◽  
Virus Type ◽  
Recombinant Vaccine ◽  
Parainfluenza Virus ◽  
Syncytial Virus ◽  
Type 3

scholarly journals Recombinant Bovine/Human Parainfluenza Virus Type 3 (B/HPIV3) Expressing the Respiratory Syncytial Virus (RSV) G and F Proteins Can Be Used To Achieve Simultaneous Mucosal Immunization against RSV and HPIV3

2001 ◽  
Vol 75 (10) ◽  
pp. 4594-4603 ◽  
Author(s):  
Alexander C. Schmidt ◽  
Josephine M. McAuliffe ◽  
Brian R. Murphy ◽  
Peter L. Collins
Keyword(s):  
Respiratory Syncytial Virus ◽  
Respiratory Tract ◽  
Host Range ◽  
Virus Type ◽  
Serum Antibody ◽  
Parainfluenza Virus ◽  
Range Restriction ◽  
Syncytial Virus ◽  
Human Parainfluenza Virus ◽  
Type 3

ABSTRACT Recombinant bovine/human parainfluenza virus type 3 (rB/HPIV3), a recombinant bovine PIV3 (rBPIV3) in which the F and HN genes were replaced with their HPIV3 counterparts, was used to express the major protective antigens of respiratory syncytial virus (RSV) in order to create a bivalent mucosal vaccine against RSV and HPIV3. The attenuation of rB/HPIV3 is provided by the host range restriction of the BPIV3 backbone in primates. RSV G and F open reading frames (ORFs) were placed under the control of PIV3 transcription signals and inserted individually into the rB/HPIV3 genome in the promoter-proximal position preceding the nucleocapsid protein gene. The recombinant PIV3 expressing the RSV G ORF (rB/HPIV3-G1) was not restricted in its replication in vitro, whereas the virus expressing the RSV F ORF (rB/HPIV3-F1) was eightfold restricted compared to its rB/HPIV3 parent. Both viruses replicated efficiently in the respiratory tract of hamsters, and each induced RSV serum antibody titers similar to those induced by RSV infection and anti-HPIV3 titers similar to those induced by HPIV3 infection. Immunization of hamsters with rB/HPIV3-G1, rB/HPIV3-F1, or a combination of both viruses resulted in a high level of resistance to challenge with RSV or HPIV3 28 days later. These results describe a vaccine strategy that obviates the technical challenges associated with a live attenuated RSV vaccine, providing, against the two leading viral agents of pediatric respiratory tract disease, a bivalent vaccine whose attenuation phenotype is based on the extensive host range sequence differences of BPIV3.

scholarly journals Inclusion Body Fusion of Human Parainfluenza Virus Type 3 Regulated by Acetylated α-Tubulin Enhances Viral Replication

2016 ◽  
Vol 91 (3) ◽  
Author(s):  
Shengwei Zhang ◽  
Yanliang Jiang ◽  
Qi Cheng ◽  
Yi Zhong ◽  
Yali Qin ◽  
...  
Keyword(s):  
Viral Replication ◽  
Virus Type ◽  
Inclusion Bodies ◽  
Viral Proteins ◽  
Cellular Proteins ◽  
Parainfluenza Virus ◽  
Syncytial Virus ◽  
Human Parainfluenza Virus ◽  
Type 3 ◽  
Efficient Viral Replication

ABSTRACT Viral inclusion bodies (IBs), or replication factories, are unique structures generated by viral proteins together with some cellular proteins as a platform for efficient viral replication, but little is known about the mechanism underlying IB formation and fusion. Our previous study demonstrated that the interaction between the nucleoprotein (N) and phosphoprotein (P) of human parainfluenza virus type 3 (HPIV3), an enveloped virus with great medical impact, can form IBs. In this study, we found that small IBs can fuse with each other to form large IBs that enhance viral replication. Furthermore, we found that acetylated α-tubulin interacts with the N-P complex and colocalizes with IBs of HPIV3 but does not interact with the N-P complex of human respiratory syncytial virus or vesicular stomatitis virus and does not colocalize with IBs of human respiratory syncytial virus. Most importantly, enhancement of α-tubulin acetylation using the pharmacological inhibitor trichostatin A (TSA), RNA interference (RNAi) knockdown of the deacetylase enzymes histone deacetylase 6 (HDAC6) and sirtuin 2 (SIRT2), or expression of α-tubulin acetyltransferase 1 (α-TAT1) resulted in the fusion of small IBs into large IBs and effective viral replication. In contrast, suppression of acetylation of α-tubulin by overexpressing HDAC6 and SIRT2 profoundly inhibited the fusion of small IBs and viral replication. Our findings offer previously unidentified mechanistic insights into the regulation of viral IB fusion by acetylated α-tubulin, which is critical for viral replication. IMPORTANCE Inclusion bodies (IBs) are unique structures generated by viral proteins and some cellular proteins as a platform for efficient viral replication. Human parainfluenza virus type 3 (HPIV3) is a nonsegmented single-stranded RNA virus that mainly causes lower respiratory tract disease in infants and young children. However, no vaccines or antiviral drugs for HPIV3 are available. Therefore, understanding virus-host interactions and developing new antiviral strategies are increasingly important. Acetylation on lysine (K) 40 of α-tubulin is an evolutionarily conserved modification and plays an important role in many cellular processes, but its role in viral IB dynamics has not been fully explored. To our knowledge, our findings are the first to show that acetylated α-tubulin enhances viral replication by regulating HPIV3 IB fusion.

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