Faculty Opinions recommendation of Secreted dengue virus nonstructural protein NS1 is an atypical barrel-shaped high-density lipoprotein.

Dengue is a mosquito-borne infectious disease highly endemic to tropical and subtropical countries. Symptomatic patients can rapidly progress to severe conditions of hemorrhage, plasma extravasation and hypovolemic shock that leads to death. Severe dengue patients’ blood tests typically report low levels of high-density lipoprotein (HDL), that is responsible for reverse cholesterol transport (RCT) and regulation of lipid composition on peripheral tissues. It is well known that Dengue virus (DENV) depends on membrane cholesterol rafts to infect and replicate in mammalian cells. Here we describe the interaction of the DENV nonstructural protein 1 (NS1) with Apolipoprotein A1 (ApoA1), which is the major protein component of HDL. NS1 is secreted by infected cells and can be found circulating in the serum of patients since the onset of the symptoms. NS1 concentration in plasma is related to dengue severity, attributed to immune evasion and acute inflammatory response. Our data show that the DENV NS1 protein induces the increase of lipid rafts in non-infected cell membrane and enhances further DENV infection. We also show that ApoA1-mediated lipid raft depletion inhibits DENV attachment to cell surface. In addition, ApoA1 was able to neutralize NS1-induced cell activation and to prevent NS1-mediated enhancement of DENV infection. Furthermore, we demonstrate that the ApoA1 mimetic peptide 4F is also capable of mediating lipid raft depletion to control DENV infection. Taken together, our results suggest the potential of RCT-based therapies for dengue treatment. These results should motivate studies to assess the importance of RCT in dengue infection in vivo. IMPORTANCE Dengue virus (DENV) is one of the most relevant mosquito-transmitted viruses worldwide, infecting more the 390 million people every year and leading to more than 20 thousand deaths. Despite a DENV vaccine has already been approved, its potential side-effects have hampered its use in large scale immunization. Therefore, new treatment options are urgent either to prevent disease worsening or improve current clinical management of severe cases. In the present study, we describe a new interaction of the NS1 protein, one of the major viral components, with a key component of high-density lipoprotein, the Apolipoprotein A1 (ApoA1). This interaction seems to alter membrane susceptibility to virus infection and modulates the mechanisms triggered by DENV to evade immune response. We also propose the use of a mimetic peptide named 4F, originally developed for atherosclerosis, as a potential therapy for relieving DENV symptoms.

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Molecularly Imprinted Polymers for Diagnostics: Sensing High Density Lipoprotein and Dengue Virus

Procedia Engineering ◽

10.1016/j.proeng.2016.11.157 ◽

2016 ◽

Vol 168 ◽

pp. 101-104 ◽

Cited By ~ 7

Author(s):

P.A. Lieberzeit ◽

S. Chunta ◽

K. Navakul ◽

C. Sangma ◽

C. Jungmann

Keyword(s):

Dengue Virus ◽

High Density Lipoprotein ◽

Molecularly Imprinted Polymers ◽

Density Lipoprotein ◽

High Density ◽

Molecularly Imprinted ◽

Imprinted Polymers

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Role of Circulating High-Density Lipoprotein and Triglycerides in Coronary Artery Disease: Risk and Prevention

Endocrinology and Metabolism Clinics of North America ◽

10.1016/s0889-8529(18)30326-8 ◽

1990 ◽

Vol 19 (2) ◽

pp. 299-309 ◽

Cited By ~ 10

Author(s):

David J. Gordon

Keyword(s):

Coronary Artery Disease ◽

Coronary Artery ◽

High Density Lipoprotein ◽

Disease Risk ◽

Density Lipoprotein ◽

High Density ◽

Coronary Artery Disease Risk ◽

Artery Disease

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Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽

10.1024/0301-1526/a000348 ◽

2014 ◽

Vol 43 (3) ◽

pp. 189-197 ◽

Cited By ~ 10

Author(s):

Yiqiang Zhan ◽

Jinming Yu ◽

Rongjing Ding ◽

Yihong Sun ◽

Dayi Hu

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

High Density Lipoprotein Cholesterol ◽

Ankle Brachial Index ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Cholesterol Ratio ◽

Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

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