Cholesterol-rich lipid rafts play a critical role in bovine parainfluenza virus type 3 (BPIV3) infection

Abstract Background: Bovine parainfluenza virus type 3 (BPIV3) infection often causes respiratory tissue damage and immunosuppression and results in bovine respiratory disease complex. Bovine respiratory disease complex is one of the major diseases in dairy cattle and causes huge economical losses every year. The pathogenetic and immunoregulatory mechanisms involved in the process of BPIV3 infection, however, remain unknown. Proteomics is a powerful tool for high-throughput identification of proteins and has been widely used to understand how viruses interact with host cells.Methods: In the present study, we report a proteomic analysis to investigate the whole cellular protein alterations of MDBK cells infected with BPIV3. To investigate the infection process of BPIV3 and the immune response mechanism of MDBK cells, isobaric tags for relative and absolute quantitation analysis (iTRAQ) and Q-Exactive mass spectrometry-based proteomics were performed. The differentially expressed proteins (DEPs) involved in the BPIV3 invasion process in MDBK cells were identified, annotated, and quantitated.Results: A total of 116 proteins, which included 74 upregulated proteins and 42 downregulated proteins, were identified as DEPs between the BPIV3-infected and the mock-infected groups. These DEPs included corresponding proteins related to inflammatory response, immune response, and lipid metabolism. These results might provide some insights for understanding the pathogenesis of BPIV3. Fluorescent quantitative PCR and western blotting analysis showed results consistent with those of iTRAQ identification. Interestingly, the upregulated protein MKK3 was associated with the p38 MAPK signaling pathway.Conclusions: The results of proteomics analysis indicated BPIV3 infection could activate the p38 MAPKpathway to promote virus replication.

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Recombinant type 5 adenoviruses expressing bovine parainfluenza virus type 3 glycoproteins protect Sigmodon hispidus cotton rats from bovine parainfluenza virus type 3 infection.

Journal of Virology ◽

10.1128/jvi.69.7.4308-4315.1995 ◽

1995 ◽

Vol 69 (7) ◽

pp. 4308-4315 ◽

Cited By ~ 9

Author(s):

M M Breker-Klassen ◽

D Yoo ◽

S K Mittal ◽

S D Sorden ◽

D M Haines ◽

...

Keyword(s):

Virus Type ◽

Parainfluenza Virus ◽

Sigmodon Hispidus ◽

Recombinant Type ◽

Cotton Rats ◽

Type 3 ◽

Bovine Parainfluenza Virus

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Isolation of a Divergent Strain of Bovine Parainfluenza Virus Type 3 (BPIV3) Infecting Cattle in China

Viruses ◽

10.3390/v11060489 ◽

2019 ◽

Vol 11 (6) ◽

pp. 489 ◽

Cited By ~ 1

Author(s):

Élcio Leal ◽

Cun Liu ◽

Zhanzhong Zhao ◽

Yong Deng ◽

Fabiola Villanova ◽

...

Keyword(s):

Virus Type ◽

Immune Escape ◽

Parainfluenza Virus ◽

Chinese Isolate ◽

Respiratory Pathogens ◽

Adult Cattle ◽

Mdbk Cells ◽

Type 3 ◽

Bovine Parainfluenza Virus ◽

Genotype A

Bovine parainfluenza virus type 3 (BPIV3) is one of the most important known viral respiratory pathogens of both young and adult cattle. It is also named “heat stress in transport”, causing morbidity and mass death. New variants of BPIV3 have been detected or isolated in China since 2008. Here, we isolate one BPIV3 strain (named BPIV3 BJ) in Madin-Darby bovine kidney (MDBK) cells from nasal samples collected in China. Phylogenetic analysis showed that our isolate is related to BPIV3 of the genotype A. The comparison of BPIV3-BJ and the reference Chinese isolate NM09 showed that these strains are highly divergent. We found many differences in the amino acid composition in the nucleocapsid (NP) protein among these genotype A strains. Since the NP protein has been implicated in immunization studies, our BPIV3 isolate will be useful for the development of immune assays and vaccine studies. The diversity of BPIV3 lineages that we found in China indicated ongoing evolution for immune escape. Our study highlights the importance of genetic surveillance for determining the effect of BPIV3 variability on pathogen evolution and population-scale immunity.

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Virion-Associated Cholesterol Regulates the Infection of Human Parainfluenza Virus Type 3

Viruses ◽

10.3390/v11050438 ◽

2019 ◽

Vol 11 (5) ◽

pp. 438 ◽

Cited By ~ 4

Author(s):

Qiaopeng Tang ◽

Pengfei Liu ◽

Mingzhou Chen ◽

Yali Qin

Keyword(s):

Lipid Rafts ◽

Virus Type ◽

Viral Envelope ◽

Parainfluenza Virus ◽

F Protein ◽

Assembly Mechanism ◽

C Terminus ◽

The Matrix ◽

Human Parainfluenza Virus ◽

Type 3

The matrix (M) proteins of paramyxoviruses bind to the nucleocapsids and cytoplasmic tails of glycoproteins, thus mediating the assembly and budding of virions. We first determined the budding characterization of the HPIV3 Fusion (F) protein to investigate the assembly mechanism of human parainfluenza virus type 3 (HPIV3). Our results show that expression of the HPIV3 F protein alone is sufficient to initiate the release of virus-like particles (VLPs), and the F protein can regulate the VLP-forming ability of the M protein. Furthermore, HPIV3F-Flag, which is a recombinant HPIV3 with a Flag tag at the C-terminus of the F protein, was constructed and recovered. We found that the M, F, and hemagglutinin-neuraminidase (HN) proteins and the viral genome can accumulate in lipid rafts in HPIV3F-Flag-infected cells, and the F protein mainly exists in the form of F1 in VLPs, lipid rafts, and purified virions. Furthermore, the function of cholesterol in the viral envelope and cell membrane was assessed via the elimination of cholesterol by methyl-β-cyclodextrin (MβCD). Our results suggest that the infectivity of HPIV3 was markedly reduced, due to defective internalization ability in the absence of cholesterol. These results reveal that HPIV3 might assemble in the lipid rafts to acquire cholesterol for the envelope of HPIV3, which suggests the that disruption of the cholesterol composition of HPIV3 virions might be a useful method for the design of anti-HPIV3 therapy.

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