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Chronic exposure to arsenite enhances influenza virus infection in cultured cells.

亚砷酸盐慢性暴露增强培养细胞中流感病毒感染。

  • 影响因子:3.14
  • DOI:10.1002/jat.3918
  • 作者列表:"Amouzougan EA","Lira R Jr","Klimecki WT
  • 发表时间:2020-01-20
Abstract

:Arsenic is a ubiquitous environmental toxicant that has been associated with human respiratory diseases. In humans, arsenic exposure has been associated with increased risk of respiratory infection. Considering the existing epidemiological evidence and the well-established impact of arsenic on epithelial cell biology, we posited that the effect of arsenic exposure in epithelial cells could enhance viral infection. In this study, we characterized influenza virus A/WSN/33 (H1N1) infection in Madin-Darby Canine Kidney (MDCK) cells chronically exposed to low levels of sodium arsenite (75 ppb). We observed a 27.3-fold increase in viral matrix (M2) protein (24 hours postinfection [p.i.]), a 1.35-fold increase in viral mRNA levels, and a 126% increase in plaque area in arsenite-exposed MDCK cells (48 hours p.i.). Arsenite exposure resulted in 114% increase in virus attachment-positive cells (2 hours p.i.) and 224% increase in α-2,3 sialic acid-positive cells. Interestingly, chronic exposure to arsenite reduced the effect of the antiviral drug, oseltamivir in MDCK cells. We also found that exposure to sodium arsenite resulted in a 4.4-fold increase in viral mRNA levels and significantly increased cytotoxicity in influenza A/Udorn/72 (H3N2) infected BEAS-2B cells. This study suggests that chronic arsenite exposure could result in enhanced influenza infection in epithelial cells, and that this may be mediated through increased sialic acid binding. Finally, the decreased effectiveness of the anti-influenza drug, oseltamivir, in arsenite-exposed cells raises substantial public health concerns if this effect translates to arsenic-exposed, influenza-infected people.

摘要

砷是一种普遍存在的环境毒物,与人类呼吸系统疾病有关。在人类中,砷暴露与呼吸道感染风险增加有关。考虑到现有的流行病学证据和砷对上皮细胞生物学的影响,我们认为砷暴露在上皮细胞中的作用可以增强病毒感染。在本研究中,我们对慢性暴露于低水平亚砷酸钠 (75 ppb) 的 Madin-Darby 犬肾 (MDCK) 细胞中流感病毒 A/WSN/33 (H1N1) 感染进行了表征。我们观察到病毒基质 (M2) 蛋白增加 27.3 倍 (感染后 24 小时 [p。 i.]), 亚砷酸盐暴露的 MDCK 细胞中病毒 mRNA 水平增加 1.35 倍,斑块面积增加 126% (48 小时 p。 i.)。亚砷酸盐暴露导致病毒附着阳性细胞增加 114% (2 小时 p.i.),α 2,3 唾液酸阳性细胞增加 224%。有趣的是,长期暴露于亚砷酸盐降低了抗病毒药物奥司他韦在 MDCK 细胞中的作用。我们还发现,暴露于亚砷酸钠导致病毒 mRNA 水平增加 4.4 倍,并显著增加流感 a/Udorn/72 (H3N2) 感染的 BEAS-2B 细胞的细胞毒性。本研究表明,慢性亚砷酸盐暴露可导致上皮细胞中流感感染增强,这可能是通过唾液酸结合增加介导的。最后,抗流感药物奥司他韦在亚砷酸盐暴露的细胞中的有效性降低,如果这种效应转化为砷暴露的流感感染者,则会引起实质性的公共卫生问题。

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发表时间:2020-01-19
DOI:10.1093/cid/ciaa050
作者列表:["Baum U","Kulathinal S","Auranen K","Nohynek H"]

METHODS:BACKGROUND:From 2015/16 through 2017/18, injectable, trivalent inactivated influenza vaccines (IIV3) and a nasal spray, tetravalent live-attenuated influenza vaccine (LAIV4) were used in parallel in Finland. To understand how well vaccination with each vaccine type protected children against influenza under real-life conditions, vaccine effectiveness in two-year-olds was estimated for all three seasons. METHODS:Each season, a nationwide register-based cohort study was conducted. The study population comprised 60,088 children in 2015/16, 60,860 children in 2016/17 and 60,345 children in 2017/18. Laboratory-confirmed influenza was the study outcome. Seasonal influenza vaccination with either LAIV4 or IIV3 was the time-dependent exposure of interest. Vaccine effectiveness was defined as 1 minus the hazard ratio comparing vaccinated with unvaccinated children. RESULTS:From 2015/16 through 2017/18, the effectiveness of LAIV4 against influenza of any virus type was estimated at 54.2% (95% confidence interval, 32.2%-69.0%), 20.3% (-12.7% to 43.6%) and 30.5% (10.9%-45.9%); the corresponding effectiveness of IIV3 was 77.2% (48.9%-89.8%), 24.5% (-29.8% to 56.1%) and -20.1% (-61.5% to 10.7%). Neither of the influenza vaccines clearly excelled in protecting children. The LAIV4 effectiveness against type B was greater than against type A and greater than the IIV3 effectiveness against type B. CONCLUSIONS:To understand how influenza vaccines could be improved, vaccine effectiveness must be analyzed by vaccine and virus type. Effectiveness estimates expressing also overall protection levels are needed to guide individual and programmatic decision-making processes. Supported by this analysis, the vaccination program in Finland now recommends LAIV4 and injectable, tetravalent inactivated influenza vaccines replacing IIV3.

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影响因子:1.36
发表时间:2020-01-20
DOI:10.1111/1348-0421.12775
作者列表:["Ainai A","van Riet E","Ito R","Ikeda K","Senchi K","Suzuki T","Tamura SI","Asanuma H","Odagiri T","Tashiro M","Kurata T","Multihartina P","Setiawaty V","Andriana Pangesti KN","Hasegawa H"]

METHODS::Intranasally administered influenza vaccines could be more effective than injected vaccines, since intranasal vaccination can induce virus-specific IgA antibodies in the upper respiratory tract, which is the initial site of infection. In the current study, immune responses elicited by an intranasal inactivated H5 influenza vaccine were evaluated in healthy H5 influenza virus-naive individuals. Three doses of intranasal inactivated whole-virion H5 influenza vaccine induced strong neutralizing nasal IgA and serum IgG antibodies. In addition, a mucoadhesive excipient, carboxy-vinyl polymer (CVP), had a notable impact on the induction of nasal IgA antibody responses but not serum IgG antibody responses. The nasal hemagglutinin (HA)-specific IgA antibody responses clearly correlated with mucosal neutralizing antibody responses, indicating that measurement of nasal HA-specific IgA titers could be used as a surrogate for the mucosal antibody response. Furthermore, increased numbers of plasma cells and vaccine antigen-specific helper T (Th) cells in the peripheral blood were observed after vaccination, suggesting that peripheral blood biomarkers may also be used to evaluate the intranasal vaccine-induced immune response. However, peripheral blood immune cell responses correlated with neutralizing antibody titers in serum samples but not in nasal wash samples. Thus, analysis of the peripheral blood immune response could be a surrogate for the systemic immune response to intranasal vaccination but not for the mucosal immune response. The current study suggests the clinical potential of intranasal inactivated vaccines against H5 influenza viruses and highlights the need to develop novel means to evaluate intranasal vaccine-induced mucosal immune responses. This article is protected by copyright. All rights reserved.

影响因子:6.53
发表时间:2020-01-21
DOI:10.1016/S1473-3099(19)30584-5
作者列表:["Liebowitz D","Gottlieb K","Kolhatkar NS","Garg SJ","Asher JM","Nazareno J","Kim K","McIIwain DR","Tucker SN"]

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