Abstract
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.
Highlights
Human parainfluenza virus type 3 (HPIV3) is an enveloped, non-segmented, negative, single-strand RNA virus, and it acts as one of the primary pathogens that causes respiratory tract diseases, including bronchiolitis, pneumonia, and croup in infants and young children
We found that the F protein of HPIV3 can form virus-like particles (VLPs) when expressed alone, and the F protein can regulate the ability of the M protein to form VLPs, which suggests that the F protein plays an important role in the assembly and budding of HPIV3
We found that HPIV3 envelope-associated cholesterol affects the fusion between the virus and the cell membrane. These results suggest that HPIV3 may acquire envelope associated-cholesterol from lipid rafts for virus infection, which provides us with a new strategy for anti-HPIV3 therapy
Summary
Human parainfluenza virus type 3 (HPIV3) is an enveloped, non-segmented, negative, single-strand RNA virus, and it acts as one of the primary pathogens that causes respiratory tract diseases, including bronchiolitis, pneumonia, and croup in infants and young children. Lipid rafts seem to be their preferred sites for budding during their life cycles for many viruses, as lipid rafts contain abundant cholesterol, sphingolipid, and proteins, which allow them to act as platforms that function in cell membrane signaling [2] and trafficking [3]. Due to the critical role of lipid rafts as platforms for virus assembly and budding, the envelopes of many viruses contain abundant cholesterol and sphingomyelin. We found that HPIV3 envelope-associated cholesterol affects the fusion between the virus and the cell membrane These results suggest that HPIV3 may acquire envelope associated-cholesterol from lipid rafts for virus infection, which provides us with a new strategy for anti-HPIV3 therapy. The mechanism of how viral envelope-associated cholesterol affects membrane fusion requires further research
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