Murine nasal-associated lymphoid tissue (NALT) harbors human alphaherpesvirus 1 (HSV-1) DNA during latency, and dexamethasone triggers viral replication.

IF 4 2区 医学 Q2 VIROLOGY
Kelly S Harrison, Shannon R Cowan, Clinton Jones
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引用次数: 0

Abstract

Human alphaherpesvirus 1 (HSV-1) acute infection causes conjunctivitis, encephalitis, genital lesions, and herpes esophagitis. Following acute infection, HSV-1 and other alpha-herpesvirinae subfamily members establish life-long latency in neurons within the trigeminal ganglia and central nervous system. Notably, certain animal alpha-herpesvirinae subfamily members, including bovine alphaherpesvirus 1 (BoHV-1), canine herpesvirus 1, equine herpesvirus 4, and pseudorabies virus, establish a quiescent/latent infection in tonsils. BoHV-1 viral gene expression and virus shedding from tonsils also occur during reactivation from latency in calves. Consequently, we tested whether nasopharyngeal lymphoid tissue (NALT) harbors HSV-1 DNA in latently infected mice because it is structurally and functionally comparable with tonsils. NALT prepared from latently infected mice consistently contained viral DNA, but infectious virus was not detected. In contrast to latently infected TG neurons, the HSV-1 latency-associated transcript was not detected in NALT of latently infected mice. HSV-1 DNA levels, immediate early RNA expression, and virus shedding were readily detected when NALT explants were cultured with a medium containing the synthetic corticosteroid dexamethasone for 48 h. Increased viral DNA and virus production were not detected in NALT explants when incubated with a medium lacking dexamethasone. Sorting cells from NALT of HSV-1 latently infected mice revealed that dendritic cells, microfold cells, and natural killer cells, but not B or T cells, harbor HSV-1 DNA, and infectious virus was readily detected when cultured in medium containing dexamethasone. In summary, certain NALT cells consistently contain viral DNA in latently infected mice, and dexamethasone triggers viral gene expression and virus production.

Importance: Human alphaherpesvirus 1 (HSV-1) acute infection causes various diseases, including herpes esophagitis. HSV-1 subsequently establishes lifelong latency in neurons within the trigeminal ganglia and central nervous system. Viral DNA, but not infectious virus, was consistently detected in nasopharyngeal lymphoid tissue (NALT) of latently infected mice. NALT is structurally and functionally comparable with the tonsils of other mammals, including humans. RNA and protein expression of infected cell protein 0 (ICP0) and ICP4 plus virus production were consistently detected when NALT explants were cultured with a medium containing dexamethasone, a synthetic corticosteroid. Sorting NALT cells from HSV-1 latently infected mice revealed dendritic cells, microfold cells, and natural killer cells that harbor HSV-1 DNA. Virus shedding was readily detected when viral DNA-positive NALT cells were cultured in a medium containing dexamethasone. These studies revealed that specific NALT cells harbor viral DNA, and dexamethasone triggered viral replication and virus production, suggesting that reactivation from a latent or quiescent infection had occurred.

小鼠鼻相关淋巴组织(NALT)在潜伏期间携带人类α疱疹病毒1 (HSV-1) DNA,地塞米松触发病毒复制。
人类α疱疹病毒1型(HSV-1)急性感染可引起结膜炎、脑炎、生殖器病变和疱疹性食管炎。急性感染后,HSV-1和其他α -疱疹病毒亚家族成员在三叉神经节和中枢神经系统的神经元中建立终身潜伏期。值得注意的是,某些动物α -疱疹病毒亚家族成员,包括牛α -疱疹病毒1 (BoHV-1)、犬α -疱疹病毒1、马α -疱疹病毒4和伪狂犬病毒,在扁桃体中建立静止/潜伏感染。BoHV-1病毒基因表达和病毒从扁桃体脱落也发生在犊牛潜伏期再激活期间。因此,我们测试了潜伏感染小鼠的鼻咽淋巴组织(NALT)是否含有HSV-1 DNA,因为它在结构和功能上与扁桃体相似。从潜伏感染小鼠制备的NALT始终含有病毒DNA,但未检测到感染性病毒。与潜伏感染的TG神经元相反,在潜伏感染小鼠的NALT中未检测到HSV-1潜伏期相关转录物。当NALT外植体在含有合成皮质类固醇地塞米松的培养基中培养48小时时,可以很容易地检测到HSV-1 DNA水平、即时早期RNA表达和病毒脱落。在不含地塞米松的培养基中培养时,NALT外植体中没有检测到病毒DNA和病毒产量的增加。从HSV-1潜伏感染小鼠的NALT中分选细胞发现,树突状细胞、微褶细胞和自然杀伤细胞携带HSV-1 DNA,而不是B细胞或T细胞,在含有地塞米松的培养基中培养时,很容易检测到感染性病毒。总之,在潜伏感染的小鼠中,某些NALT细胞始终含有病毒DNA,地塞米松触发病毒基因表达和病毒产生。重要性:人类甲型疱疹病毒1型(HSV-1)急性感染可引起多种疾病,包括疱疹性食管炎。HSV-1随后在三叉神经节和中枢神经系统的神经元中建立终身潜伏期。在潜伏感染小鼠鼻咽淋巴组织(NALT)中一致检测到病毒DNA,但未检测到感染性病毒。NALT在结构和功能上与包括人类在内的其他哺乳动物的扁桃体相当。用含地塞米松(一种合成皮质类固醇)的培养基培养NALT外植体时,可以一致检测到感染细胞蛋白0 (ICP0)和ICP4的RNA和蛋白表达以及病毒的产生。从潜伏感染HSV-1的小鼠中分选NALT细胞,发现树突状细胞、微褶细胞和自然杀伤细胞含有HSV-1 DNA。当病毒dna阳性的NALT细胞在含有地塞米松的培养基中培养时,很容易检测到病毒脱落。这些研究表明,特定的NALT细胞含有病毒DNA,地塞米松触发病毒复制和病毒产生,表明潜伏或静止感染的再激活已经发生。
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来源期刊
Journal of Virology
Journal of Virology 医学-病毒学
CiteScore
10.10
自引率
7.40%
发文量
906
审稿时长
1 months
期刊介绍: Journal of Virology (JVI) explores the nature of the viruses of animals, archaea, bacteria, fungi, plants, and protozoa. We welcome papers on virion structure and assembly, viral genome replication and regulation of gene expression, genetic diversity and evolution, virus-cell interactions, cellular responses to infection, transformation and oncogenesis, gene delivery, viral pathogenesis and immunity, and vaccines and antiviral agents.
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