Alcohol intake alters immune responses and promotes CNS viral persistence in mice.
Alcohol intake alters immune responses and promotes CNS viral persistence in mice.
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DOI：
10.1016/j.bbr.2016.06.006
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发表时间：
2016-10-01
影响因子：
2.7
通讯作者：
Huang E
中科院分区：
文献类型：
--
作者：
Loftis JM;Taylor J;Raué HP;Slifka MK;Huang E
慢性丙型肝炎病毒感染会导致进行性肝病，并与多种肝外效应有关，包括中枢神经系统(CNS)损害和神经精神障碍。酒精滥用会加剧这些对大脑和行为的不利影响，但其分子机制尚不清楚。这项研究探讨了酒精对感染淋巴细胞性脉络膜脑膜炎病毒(LCMV)的小鼠的病毒持久性和中枢神经系统免疫病理的调节作用。雌性和雄性BALB/c小鼠(n=94)使用两瓶选择范式暴露于酒精(乙醇；乙醇；乙醇)和水(或仅水)，一周后，感染LCMV克隆13(引起类似慢性丙型肝炎的慢性感染)、LCMV阿姆斯特朗(引起急性感染)或载体。小鼠在感染后被监测60天，并继续获得24小时的乙醇和水。与急性或未感染病毒的动物相比，感染LCMV克隆13的动物饮用更多的乙醇。在感染LCMV克隆13六周后，与未接触乙醇的小鼠相比，接触乙醇的小鼠的血清病毒滴度更高。乙醇摄入还与病毒特异性CD8+T细胞频率(特别是CD11ahi亚群)的减少以及慢性感染小鼠持续的中枢病毒血症的证据有关。这些发现支持乙醇使用和慢性病毒感染可导致联合毒性效应、加速中枢神经系统损伤和神经精神功能障碍的假说，并表明研究乙醇在调节LCMV感染小鼠的病毒持久性和中枢神经系统免疫病理中的作用可以更全面地了解酒精使用障碍和慢性病毒感染的并存情况。
Chronic hepatitis C virus (HCV) infection leads to progressive liver disease and is associated with a variety of extrahepatic effects, including central nervous system (CNS) damage and neuropsychiatric impairments. Alcohol abuse can exacerbate these adverse effects on brain and behavior, but the molecular mechanisms are not well understood. This study investigated the role of alcohol in regulating viral persistence and CNS immunopathology in mice infected with lymphocytic choriomeningitis virus (LCMV), a model for HCV infections in humans. Female and male BALB/c mice (n = 94) were exposed to alcohol (ethanol; EtOH) and water (or water only) using a two-bottle choice paradigm, followed one week later by infection with either LCMV clone 13 (causes chronic infection similar to chronic HCV), LCMV Armstrong (causes acute infection), or vehicle. Mice were monitored for 60 days post-infection and continued to receive 24-hour access to EtOH and water. Animals infected with LCMV clone 13 drank more EtOH, as compared to those with an acute or no viral infection. Six weeks after infection with LCMV clone 13, mice with EtOH exposure evidenced higher serum viral titers, as compared to mice without EtOH exposure. EtOH intake was also associated with reductions in virus-specific CD8+ T cell frequencies (particularly CD11ahi subsets) and evidence of persistent CNS viremia in chronically infected mice. These findings support the hypothesis that EtOH use and chronic viral infection can result in combined toxic effects accelerating CNS damage and neuropsychiatric dysfunction and suggest that examining the role of EtOH in regulating viral persistence and CNS immunopathology in mice infected with LCMV can lead to a more comprehensive understanding of comorbid alcohol use disorder and chronic viral infection.
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DOI：
10.1111/j.1530-0277.2007.00479.x
发表时间：
2007-10-01
影响因子：
3.2
作者：
Heinz, Richard;Waltenbaugh, Carl
通讯作者：
Waltenbaugh, Carl
影响因子：
4.4
作者：
Homann, D;McGavern, DB;Oldstone, MBA
通讯作者：
Oldstone, MBA
影响因子：
13.5
作者：
Forton, DM;Thomas, HC;Taylor-Robinson, SD
通讯作者：
Taylor-Robinson, SD
影响因子：
3.6
作者：
Forton, DM;Thomas, HC;Taylor-Robinson, SD
通讯作者：
Taylor-Robinson, SD
影响因子：
3.7
作者：
Beier JI;Jokinen JD;Holz GE;Whang PS;Martin AM;Warner NL;Arteel GE;Lukashevich IS
通讯作者：
Lukashevich IS