单纯疱疹病毒
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单纯疱疹病毒 | ||||||||
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TEM 单纯疱疹病毒显微照片 . | ||||||||
病毒分類 | ||||||||
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Herpes simplex virus 1 (HSV-1) |
单纯疱疹病毒(herpes simplex virus; HSV) 1 和 2 (HSV-1 和 HSV-2),也叫人类单纯疱疹病毒 1 和 2 (HHV-1 and -2),是疱疹病毒科(Herpesviridae)中的感染人类的两类。[1] HSV-1 和 -2都是普遍存在且接触传染的。当患者产生和释放病毒时,单纯疱疹病毒就会传播。第一類型單純疱疹(HSV-1)與口腔周圍、眼角膜結膜炎及上半身感染的皮膚炎有關;第二類型單純疱疹(HSV-2)則與生殖器、新生兒疱疹及下半身感染的皮膚炎有關。[2]。
单纯疱疹病毒感染症状包括口、唇或生殖器的皮肤或粘液膜上出现水泡。[1] 病灶显示疱疹状的病毒典型的痂。在病发时,病毒会产生非常轻微或异常症状。 然而,作为亲神经的和神经侵入性的病毒,HSV-1和-2通过潜伏并避开免疫系统,驻留在人体神经细胞内。在第一次感染后,部分患者经历病毒再激活或暴发散发期。 发病时,神经细胞中的病毒变得活跃,通过神经轴突转移到皮肤,出现病毒复制和释放,导致新的疼痛。[3]
目录
1 传播
2 微生物学
2.1 病毒结构
2.2 进入细胞
2.3 免疫
2.4 复制
2.5 潜伏性感染
3 治疗和疫苗开发
4 和阿尔茨海默病的关系
5 参考文献
6 外部連結
传播
HSV-1和-2是通过接触病毒复发期皮肤感染区而传染的。潜伏期,疱疹病毒并不传染。在病毒症状复发期,伴有可见的和典型的皮肤疼痛,传染很可能发生。无症状的复发是指病毒导致非典型的、轻微的或不明显的症状,不能确认为发病疱疹症状。非典型症状通常归咎于其他原因,如酵母菌感染[4][5] 。HSV-1是通常幼儿期口传染的,但也可能是性传染的。 HSV-2主要是性传染的,但HSV-1生殖器感染率正不断增长[4]。
尽管可能性很小,两种病毒也都可能通过分娩传染的[6] 。如果母亲在分娩时没有症状或爆开的水泡,传染的可能性极小。母亲在怀妊晚期首次得此病毒,传染的可能性极大[7]。
通常第一次感染HSV时,疱疹症状会最严重,因为身体里还没有生殖器疱疹抗体来帮助你抵抗疱疹病毒。首次口腔疱疹(口腔疼痛)发作≈1%可能发展成无菌性脑膜炎[1]。
微生物学
病毒结构
動物疱疹病毒有相同的特性。疱疹病毒的結構包含了相當大的雙絞股、線性的DNA基因組,以稱為衣殼的正二十面體蛋白質外殼,衣殼又被稱為病毒包膜(envelope)的脂雙層(lipid bilayer)包起。
The open reading frames (ORFs) of HSV-1[8][9] | |||||
| 基因 | 蛋白質 | 功能/描述 | 基因 | 蛋白質 | 功能/描述 |
| UL1 | 糖蛋白 L [1] | Surface and membrane | UL38 | UL38; VP19C [2] | Capsid assembly and DNA maturation |
| UL2 | UL2 [3] | Uracil-DNA glycosylase | UL39 | UL39 [4] | Ribonucleotide reductase (Large subunit) |
| UL3 | UL3 [5] | unknown | UL40 | UL40 [6] | Ribonucleotide reductase (Small subunit) |
| UL4 | UL4 [7] | unknown | UL41 | UL41; VHS [8] | Tegument protein; Virion host shutoff[10] |
| UL5 | UL5 [9] | DNA複製 | UL42 | UL42 [10] | DNA polymerase processivity factor |
| UL6 | UL6 [11] | Processing and packaging DNA | UL43 | UL43 [12] | Membrane protein |
| UL7 | UL7 [13] | Virion maturation | UL44 | Glycoprotein C [14] | Surface and membrane |
| UL8 | UL8 [15] | DNA helicase/引发酶 complex-associated protein | UL45 | UL45 [16] | Membrane protein; C-type lectin[11] |
| UL9 | UL9 [17] | Replication origin-binding protein | UL46 | VP11/12 [18] | Tegument proteins |
| UL10 | Glycoprotein M [19] | Surface and membrane | UL47 | UL47; VP13/14 [20] | Tegument protein |
| UL11 | UL11 [21] | virion exit and secondary envelopment | UL48 | VP16 (Alpha-TIF) [22] | Virion maturation; activate IEGs by interacting with the cellular transcription factors Oct-1 and HCF. Binds to the sequence 5'TAATGARAT3'. |
| UL12 | UL12 [23] | Alkaline exonuclease | UL49 | UL49A [24] | Envelope protein |
| UL13 | UL13 [25] | Serine-threonine protein kinase | UL50 | UL50 [26] | dUTP diphosphatase |
| UL14 | UL14 [27] | Tegument protein | UL51 | UL51 [28] | Tegument protein |
| UL15 | Terminase [29] | Processing and packaging of DNA | UL52 | UL52 [30] | DNA helicase/primase complex protein |
| UL16 | UL16 [31] | Tegument protein | UL53 | Glycoprotein K [32] | Surface and membrane |
| UL17 | UL17 [33] | Processing and packaging DNA | UL54 | IE63; ICP27 [34] | Transcriptional regulation |
| UL18 | VP23 [35] | Capsid protein | UL55 | UL55 [36] | Unknown |
| UL19 | VP5 [37] | Major capsid protein | UL56 | UL56 [38] | Unknown |
| UL20 | UL20 [39] | Membrane protein | US1 | ICP22; IE68 [40] | Viral replication |
| UL21 | UL21 [41] | Tegument protein[12] | US2 | US2 [42] | Unknown |
| UL22 | Glycoprotein H [43] | Surface and membrane | US3 | US3 [44] | Serine/threonine-protein kinase |
| UL23 | Thymidine kinase [45] | Peripheral to DNA replication | US4 | Glycoprotein G [46] | Surface and membrane |
| UL24 | UL24 [47] | unknown | US5 | Glycoprotein J [48] | Surface and membrane |
| UL25 | UL25 [49] | Processing and packaging DNA | US6 | Glycoprotein D [50] | Surface and membrane |
| UL26 | P40; VP24; VP22A [51] | Capsid protein | US7 | Glycoprotein I [52] | Surface and membrane |
| UL27 | Glycoprotein B [53] | Surface and membrane | US8 | Glycoprotein E [54] | Surface and membrane |
| UL28 | ICP18.5 [55] | Processing and packaging DNA | US9 | US9 [56] | Tegument protein |
| UL29 | UL29; ICP8 [57] | Major DNA-binding protein | US10 | US10 [58] | Capsid/Tegument protein |
| UL30 | DNA polymerase [59] | DNA replication | US11 | US11; Vmw21 [60] | Binds DNA and RNA |
| UL31 | UL31 [61] | Nuclear matrix protein | US12 | ICP47; IE12 [62] | Inhibits MHC class I pathway by preventing binding of antigen to TAP |
| UL32 | UL32 [63] | Envelope glycoprotein | RS1 | ICP4; IE175 [64] | Activates gene transcription |
| UL33 | UL33 [65] | Processing and packaging DNA | ICP0 | ICP0; IE110; α0 [66] | E3 ubiquitin ligase that activates viral gene transcription and counteracts the interferon response |
| UL34 | UL34 [67] | Inner nuclear membrane protein | LRP1 | LRP1 [68] | Latency-related protein |
| UL35 | VP26 [69] | Capsid protein | LRP2 | LRP2 [70] | Latency-related protein |
| UL36 | UL36 [71] | Large tegument protein | RL1 | RL1; ICP34.5 [72] | Neurovirulence factor. Antagonizes PKR by de-phosphorylating eIF4a. |
| UL37 | UL37 [73] | Capsid assembly | LAT | none [74] | Latency-associated transcript |
进入细胞
免疫
复制
潜伏性感染
HSV-1 → 三叉神經節
HSV-2 → 仙骨神經節
治疗和疫苗开发
- 阿昔洛韦
作用機轉:由遭受疱疹病毒感染之細胞選擇性吸收,並由細胞內病毒胸苷激酶(thymidine kinase)轉變成活性三磷酸鹽型式,併入病毒DNA鏈中,干擾病毒DNA聚合酶(DNA polymerase),終結DNA鏈,阻斷病毒複製,胸苷激酶僅存於病毒中,因此本藥對人體毒性小,可選擇性抗病毒,且藥效佳;本藥除口服、靜脈注射給藥,亦可外用塗抹,吸收後分布廣,可進入中樞神經系統作用,以原型藥物由腎臟排出。[2]。
- 阿糖腺苷
作用機轉:又稱Ara-A,有效對抗DNA病毒,是嘌呤核苷酸類似物,可抑制病毒DNA聚合酶,阻斷病毒DNA複製與合成。[2]。
- 碘苷
作用機轉:又稱IDU,構造與胸腺嘧啶類似,可嵌入病毒的DNA中,而阻斷病毒DNA合成與複製,治療指數小,限用於單純疱疹性角膜炎。[2]。
和阿尔茨海默病的关系
参考文献
^ 1.01.11.2 Ryan KJ, Ray CG (editors). Sherris Medical Microbiology 4th. McGraw Hill. 2004: 555–62. ISBN 0838585299.
^ 2.02.12.22.3 蔡秋帆、湯念湖、王耀宏合著. 藥理學 2014. 新文京開發有限公司. 2014.
^ Herpes simplex. DermNet NZ — New Zealand Dermatological Society. 2006-09-16 [2006-10-15].
^ 4.04.1 Gupta R, Warren T, Wald A. Genital herpes. Lancet. 2007, 370 (9605): 2127–37. PMID 18156035. doi:10.1016/S0140-6736(07)61908-4.
^ Koelle DM, Corey L. Herpes simplex: insights on pathogenesis and possible vaccines. Annual Review of Medicine. 2008, 59: 381–95. PMID 18186706. doi:10.1146/annurev.med.59.061606.095540.
^ Corey L, Wald A. Maternal and Neonatal Herpes Simplex Virus Infections. New England Journal of Medicine. 2009, 361 (14): 1376–85. PMC 2780322. PMID 19797284. doi:10.1056/NEJMra0807633.
^ Kimberlin DW. Herpes simplex virus infections of the newborn. Semin. Perinatol. 2007, 31 (1): 19–25. PMID 17317423. doi:10.1053/j.semperi.2007.01.003.
^ McGeoch DJ, Rixon FJ, Davison AJ. Topics in herpesvirus genomics and evolution. Virus Res. 2006, 117 (1): 90–104. PMID 16490275. doi:10.1016/j.virusres.2006.01.002.
^ Search in UniProt Knowledgebase (Swiss-Prot and TrEMBL) for: HHV1
^ Matis J, Kúdelová M. Early shutoff of host protein synthesis in cells infected with herpes simplex viruses. Acta Virol. 2001, 45 (5-6): 269–77. PMID 12083325.
^ Wyrwicz LS, Ginalski K, Rychlewski L. HSV-1 UL45 encodes a carbohydrate binding C-type lectin protein. Cell Cycle. 2007, 7 (2): 269–71. PMID 18256535.
^ Vittone V, Diefenbach E, Triffett D, Douglas MW, Cunningham AL, Diefenbach RJ. Determination of interactions between tegument proteins of herpes simplex virus type 1. J. Virol. 2005, 79 (15): 9566–71. PMC 1181608. PMID 16014918. doi:10.1128/JVI.79.15.9566-9571.2005.
外部連結
- 微生物免疫學-Herpesviridae(皰疹病毒科)
- 单纯疱疹病毒中心在斯坦福大学
- Mayo Clinic on Cold Sores
- Genital Herpes - Public Health Agency of Canada
- UK Genital Herpes Resource Site
- NHS Health Encyclopaedia - Information on Cold Sores
- American Social Health Association article on differences between HSV-1 and -2
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