Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses

Bajimaya, Shringkhala; Hayashi, Tsuyoshi; Frankl, Tünde; Bryk, Peter; Ward, Brian M.; Takimoto, Toru

doi:10.1016/j.virol.2016.11.011

Cited by 30 publications

(46 citation statements)

References 48 publications

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“…1B). These results indicate that cholesterol reducing agents are effective in blocking infectious virus production of IAV and RSV similar to hPIV1, as we previously reported (Bajimaya et al, 2017). …”

Section: Resultssupporting

confidence: 88%

“…Cells treated with Gem (400 μM) and Lov (40 μM) for 24 h were infected with the viruses at MOI of 0.5 for 24 h. Cells were then fixed and the number of infected cells were determined by immunostaining using specific anti-NP monoclonal antibodies (mAb). We did not detect any difference in the number of infected cells, even though cellular cholesterol was reduced by 20% by both agents at 24 h (Bajimaya et al, 2017). These data suggested that reduced infectious virus production was not due to limited initial infection (Fig.…”

Section: Resultsmentioning

confidence: 84%

“…We previously reported that treatment of A549 cells with Gem (400 μM) and Lov (40 μM), individually or in combination did not affect cell viability, but significantly reduced cellular cholesterol. When the cells were treated with both drugs, cellular cholesterol was depleted by 20% and 44% at 24 h and 48 h, respectively (Bajimaya et al, 2017). First, we determined the production of infectious IAV A/California/04/2009 (H1N1) and A/Victoria/361/2011 (H3N2), which are currently circulating IAV subtypes.…”

Section: Resultsmentioning

confidence: 99%

“…We previously showed that FDA-approved cholesterol reducing agents, gemfibrozil (Gem) and lovastatin (Lov), efficiently reduce the cellular cholesterol level in human airway A549 cells, especially when cells were treated with both agents (Bajimaya et al, 2017). Gem is a lipid lowering fibrate, which causes intracellular cholesterol efflux decreasing storage of cellular cholesterol, and Lov inhibits cholesterol biosynthesis (Maron et al, 2000; Roy and Pahan, 2009).…”

Section: Introductionmentioning

confidence: 99%

“…Gem is a lipid lowering fibrate, which causes intracellular cholesterol efflux decreasing storage of cellular cholesterol, and Lov inhibits cholesterol biosynthesis (Maron et al, 2000; Roy and Pahan, 2009). Depletion of cholesterol by Gem and Lov disrupted lipid raft integrity and decreased hPIV1 protein association with the lipid raft domains, inhibiting virus assembly and virus particle production (Bajimaya et al, 2017). However, a previous study on IAV reported that depletion of cholesterol by MβCD enhanced IAV budding from the infected cells (Barman and Nayak, 2007), suggesting that the requirement of cholesterol for virus assembly and release may vary among respiratory RNA viruses.…”

Section: Introductionmentioning

confidence: 99%

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Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses

et al. 2017

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Cholesterol-rich lipid raft microdomains in the plasma membrane are considered to play a major role in the enveloped virus lifecycle. However, the functional role of cholesterol in assembly, infectivity and stability of respiratory RNA viruses is not fully understood. We previously reported that depletion of cellular cholesterol by cholesterol-reducing agents decreased production of human parainfluenza virus type 1 (hPIV1) particles by inhibiting virus assembly. In this study, we analyzed the role of cholesterol on influenza A virus (IAV) and respiratory syncytial virus (RSV) production. Unlike hPIV1, treatment of human airway cells with the agents did not decrease virus particle production. However, the released virions were less homogeneous in density and unstable. Addition of exogenous cholesterol to the released virions restored virus stability and infectivity. Collectively, these data indicate a critical role of cholesterol in maintaining IAV and RSV membrane structure that is essential for sustaining viral stability and infectivity.

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Section: Resultssupporting

confidence: 88%

Section: Resultsmentioning

confidence: 84%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses

et al. 2017

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Peripheral blood parameters for predicting PICU admission and mechanical ventilation in pediatric inpatients with human parainfluenza virus‐induced pneumonia

Chu

Liu

et al. 2023

Journal of Medical Virology

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Human parainfluenza viruses (hPIVs)-induced pneumonia is an important cause of pediatric hospitalization, and some develop severe pneumonias requiring pediatric intensive care unit (PICU) admission and mechanical ventilation (MV). The aim of this study is to investigate the value of peripheral blood (PB) parameters available on admission in predicting the need for PICU admission and MV due to pneumonia caused by hPIVs. A total of 331 cases including 277 (83.69%) on the general ward (GW) and 54 (16.31%) on the PICU were enrolled between January 2016 and June 2021. Of 54 patients admitted to the PICU, 24 patients (7.25%) received MV, whereas 30 (9.06%) did not. For both the PICU and GW groups, infants accounted for the highest proportion while school children had the lowest. Compared with the GW group, the PICU group had significantly higher rates of premature birth, fatigue, sore throat, headache, chest pain, tachypnea, dyspnea, and underlying diseases including congenital tracheal stenosis, congenital heart disease (CHD), metabolic disorder, and neurological disorder (ND), but significant lower proportion of exclusive breastfeeding and Z-scores for weight-for-height, weight-for-age, heightfor-age, and body-mass-index (BMI)-for-age (BMIZ). Higher levels of some leukocyte differential counts (LDC)-related parameters including counts of neutrophil (N), ratios of neutrophil-to-lymphocyte ratio (NLR), derived neutrophils/(leukocytes minus neutrophils) ratio (dNLR), and platelet-to-lymphocyte ratio (PLR), lower levels of some other LDC-related parameters including lymphocyte (L) and monocyte (M) counts, ratios of lymphocyte-to-monocyte ratio (LMR), lymphocyte-to-C-reactive protein ratio, and prognostic nutritional index (PNI), and lower levels of PB protein (PBP)-related parameters including red blood cell (RBC), hemoglobin, total protein (TP), and serum albumin were observed in the PB of patients in the PICU compared with those in the GW. Notably, higher PLR level and two comorbidities including CHD and ND were identified as independent risk factors for PICU admission, while lower PNI level as well as smaller numbers of RBC and L as good predictors. Low levels of TP might be a useful predictor of the need for MV. Overall, the relative contributions of LDC-and PBP-related factors for accurate identification of patients

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Viral modulation of lipid rafts and their potential as putative antiviral targets

Gee

Sea

Lal

2022

Reviews in Medical Virology

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Lipid rafts are ubiquitous in cells. They are identified as cholesterol and glycosphingolipid enriched microdomains on cellular membranes. They serve as platforms for cellular communications by functioning in signal transduction and membrane trafficking. Such structural organisation fulfils cellular needs for normal function, but at the same time increases vulnerability of cells to pathogen invasion. Viruses rely heavily on lipid rafts in basically every stage of the viral life cycle for successful infection. Various mechanisms of lipid rafts modification exploited by diverse viruses for attachment, internalisation, membrane fusion, genome replication, assembly and release have been brought to light. This review focuses on virus-raft interactions and how a wide range of viruses manipulate lipid rafts at distinct stages of infection. The importance of virus-raft interactions in viral infections has inspired researchers to discover and develop antivirals that target this interaction, such as statins, methyl-β-cyclodextrin, viperin, 25-hydroxycholesterol and even antimalarial drugs. The therapeutic modulations of lipid rafts as potential antiviral intervention from in vitro and in vivo evidence are discussed herein.

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Cholesterol reducing agents inhibit assembly of type I parainfluenza viruses

Cited by 30 publications

References 48 publications

Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses

Cholesterol is required for stability and infectivity of influenza A and respiratory syncytial viruses

Peripheral blood parameters for predicting PICU admission and mechanical ventilation in pediatric inpatients with human parainfluenza virus‐induced pneumonia

Viral modulation of lipid rafts and their potential as putative antiviral targets

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