Wild-type human parainfluenza virus type 3 (HPIV-3) is a significant respiratory pathogen, primarily infecting infants, young children, and immunocompromised individuals. The virus is transmitted through direct contact with respiratory secretions or aerosolized droplets from infected individuals. Upon entry, HPIV-3 targets epithelial cells lining the upper and lower respiratory tracts, binding to sialic acid receptors via its hemagglutinin-neuraminidase (HN) glycoprotein. Viral replication in these cells causes cytopathic effects, leading to inflammation and symptoms such as runny nose, cough, and fever, and in severe cases, even bronchiolitis or pneumonia. The immune response, particularly interferon, plays a key role in controlling infection. However, HPIV-3 employs mechanisms to evade innate immunity, such as inhibiting interferon signaling through its nonstructural proteins.
HPIV-3 belongs to the Paramyxoviridae family. The virion is a polymorphic, enveloped virus approximately 150-300 nanometers in diameter. Its lipid bilayer membrane is studded with two key glycoproteins: hemagglutinin-neuraminidase (HN), responsible for receptor binding and viral release, and fusion protein (F), which mediates host cell membrane fusion. Beneath the envelope lies a layer of matrix protein (M), which provides structural integrity. The viral core consists of a single-stranded, negative-sense RNA genome (approximately 15.5 kb), tightly encapsidated by a nucleoprotein (N) and associated with a phosphoprotein (P) and a large RNA-dependent RNA polymerase (L). The paramyxovirus genome encodes six major proteins (N, P, M, F, HN, and L) as well as two nonstructural proteins (C and V), which are derived from alternative open reading frames in the P gene. These accessory proteins modulate host immune responses, enhancing viral replication and pathogenesis.
Human parainfluenza virus type 3 (HPIV3) can induce pneumonia and bronchiolitis in infants and children when it infects lower respiratory tract epithelial cells and may cause asthma attacks in children and adults. Here, researchers evaluated the effects of HPIV3 infection on cultured human nasal epithelial cells (HNEC) and their release of interferon-γ and other cytokines. HPIV3-infected HNEC did not induce cytotoxicity for at least 48 h, but interferon-γ (IFN-γ) protein concentrations in cell supernatants were significantly increased at 24 and 48 h after infection (by 387% and 485%, respectively, compared with mock-infected cells). IFNγ mRNA expression was significantly increased 24 h after infection. RANTES protein concentrations and mRNA expression were significantly increased 72 h after infection. No measurable concentrations of TNF-α, IL-10, TSLP, IL-8, GM-CSF, or eotaxin were detected in the supernatants of virus-infected cells. Thus, HPIV3 can efficiently infect upper airway epithelial cells, and infection is associated with the induction of IFN-γ and the production of RANTES.
In the supernatant of uninfected cells, IFN-γ protein was detectable at 24 h (mean concentration 3.2 ± 1.2 pg/mL), 48 h (mean concentration 2.8 ± 0.9 pg/mL), and 72 h (mean concentration 2.9 ± 1.9 pg/mL). After PIV3 infection, IFN-γ protein levels increased significantly at 24 h (mean concentration 387%) and 48 h (mean concentration 485%), but decreased significantly at 72 h (Figure 1A). Compared with mock-infected cells, IFN-γ protein concentrations at all three multiplicity of infection (MOI) levels increased significantly at 24 h (mean 10.2 ± 3.1 pg/mL for MOI 0.001, mean 12.4 ± 2.9 pg/mL for MOI 0.01, and mean 14.8 ± 2.3 pg/mL for MOI 0.1) (Figure 1B). After 24 hours of infection, the expression of IFN-γ mRNA increased significantly by 174% compared with the uninfected control group, and decreased by 28% and 66% at 48 hours and 72 hours after infection, respectively, compared with the control group (Figure 1C).
Figure 1. PIV-3 induced IFN-γ protein release and mRNA expression in RPMI 2650 cells. (Lewandowska-Polak A, et al., 2015)
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Creative Biogene's Parainfluenza Type 3 is a high-quality product. We achieved excellent viral recovery in our animal challenge studies, and the growth curve in cell culture was textbook perfect.
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