抗水痘-带状疱疹病毒药物的研究进展

水痘-带状疱疹病毒(Varicella-Zoster Virus,VZV)是一种α疱疹病毒。VZV的初次感染会引发水痘,之后潜伏于神经节中。VZV的再激活会导致带状疱疹和其他多种神经性疾病。目前阿昔洛韦是首选的抗水痘-带状疱疹病毒药物,近年来其它一些处于研究中的抗水痘-带状疱疹病毒药物都表现出较好的抗病毒活性。     

水痘-带状疱疹病毒基因型的研究进展

水痘-带状疱疹病毒(VZV)属疱疹病毒α亚科,为双链DNA病毒,原发感染引起具有高度传染性的世界流行性疾病--水痘,潜伏感染再激活可导致带状疱疹.水痘-带状疱疹病毒虽然是人类疱疹病毒中最具遗传稳定性的一种病毒,但其基因组内仍存在多个单一核苷酸的变异,其中有些已成为VZV基因组内单核苷酸多态性(SNP)标记.目前已有几个研究组依据不同的SNP组合,将世界各地流行的VZV株划分为3～4个基因型.本文就VZV基因分型的研究状况进行综述.     

自体输血与异体输血对胃癌患者血浆IL-2 IL-6和IL-10的影响

带状疱疹后神经痛（postherpetic neuralgia,PHN）是指急性带状疱疹（acute herpes zoster,AHz）消退后即皮疹痊愈后,患处出现的持续性疼痛。疼痛可很严重并可伴有沿感染部位分布的瘙痒。VZV是通过早先感染水痘而获得部分免疫力人群潜伏的水痘一带状病毒（varieella—zoster virus,VZV）被激活所致。VZV感染神经节及其神经分布区域,疼痛沿受累神经分布的相应区域分批出现丛生样小水疱为特征。     

带状疱疹疫苗研究开发进展

水痘和带状疱疹(herpes zoster, HZ)是由水痘-带状疱疹病毒(varicella-zoster virus, VZV)感染引起的两种不同疾病。VZV初次感染后潜伏于脊髓或脑神经节中。HZ是机体免疫力降低、潜伏的VZV被激活后产生的疱疹样疾病, 并导致神经组织、皮肤组织的损害。目前尚无治疗HZ的特效药, HZ疫苗可有效降低HZ发生率、复发率, 减少相关后遗症和并发症。此文对已上市和开发中的HZ疫苗现状进行综述, 为新型HZ疫苗研发提供参考。     

带状疱疹疫苗研究开发进展

水痘和带状疱疹（herpes zoster,HZ）是由水痘-带状疱疹病毒（varicella-zoster virus,VZV）感染引起的两种不同疾病。VZV初次感染后潜伏于脊髓或脑神经节中。HZ是机体免疫力降低、潜伏的VZV被激活后产生的疱疹样疾病,并导致神经组织、皮肤组织的损害。目前尚无治疗HZ的特效药,HZ疫苗可有效降低HZ发生率、复发率,减少相关后遗症和并发症。此文对已上市和开发中的HZ疫苗现状进行综述,为新型HZ疫苗研发提供参考。     

水痘-带状疱疹病毒的免疫逃避

水痘-带状疱疹病毒(varicella-zoster virus,VZV)在易感人群中的初次感染引起水痘或隐性感染,当宿主的免疫系统控制了初次感染后,病毒就在宿主的感觉神经节处潜伏下来,当病毒再次活动时,就引起了带状疱疹[1～3].VZV初次感染引起水痘或隐性感染、潜伏感染及再活动致病都存在VZV的免疫逃避机理.近年来国内外的研究发现,VZV的免疫逃避机理主要包括影响MHCⅠ、MHCⅡ、细胞间黏附分子1(ICAM-1)的表达及改变树突状细胞(DCs)的功能等,现综述如下.     

免疫抑制患者神经系统常见病毒感染性疾病的临床研究进展

由于抑制病毒复制的免疫机制遭到破坏,神经系统潜伏病毒可能会被重新激活并导致感染发生,这些病毒包括人类免疫缺陷病毒（HIV）、单纯疱疹病毒（HSV）、水痘-带状疱疹病毒（VZV）、巨细胞病毒（CMV）、EB病毒（EBV）、人类疱疹病毒6型（HHV-6）、人多瘤病毒（JCV）、新型冠状病毒肺炎（COVID-19）等。免疫抑制患者神经系统病毒感染具有后遗症严重、病死率较高特点,尽早诊断、及时治疗或可改善预后,为此需了解相关临床研究进展。     

带状疱疹80例临床特点分析

<正>带状疱疹为水痘-带状疱疹病毒(VZV)所引起的急性炎症性皮肤病,VZV是一种具有亲神经性和亲皮肤性的病毒,人是VZV的唯一宿主,病毒经通过皮肤的感觉神经末梢或鼻黏膜侵入人体血液,形成病毒血症,发生水痘或隐形感染,以后病毒可以长期潜伏在人体的脊髓后根神经节或     

对候选的水痘-带状疱疹病毒糖蛋白亚单位疫苗加强免疫的应答

水痘-带状疱疹病毒(VZV)不仅可引起儿童期水痘,而且可以长期潜隐在背根神经节,一旦活化,可导致成人或老年人的带状疱疹。目前美国正用VZV减毒活疫苗来预防儿童期水痘和增强成人的免疫应答,但它同样有在感觉神经节潜伏的危险,且其长期保     

神经外科重症监护病房病人头面部带状疱疹的护理

头面部带状疱疹是由水痘-带状疱疹病毒侵犯三叉神经半月节、面神经膝状神经节及颈神经节所致的急性渗出性皮肤病[1].水痘-带状疱疹病毒初次感染表现为水痘,以后病毒可长期潜伏在三叉神经半月节、面神经膝状神经节及颈神经节,当患者免疫功能减弱时可诱发水痘-带状疱疹病毒再度活动,生长繁殖,发生头面部带状疱疹.     

Emerging drugs for varicella-zoster virus infections

INTRODUCTION: Varicella-zoster virus (VZV) is the etiological agent of two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs following primary infection, while herpes zoster (usually associated with ageing and immunosuppression) is the consequence of reactivation of the latent virus. Post-herpetic neuralgia is the major complication of shingles. AREAS COVERED: This review will discuss vaccination strategies and the current status of antivirals against VZV. A live attenuated vaccine, Varivax, is available for pediatric varicella while Zostavax was developed to boost VZV-specific cell-mediated immunity in adults older than 60 years and, via this mechanism, to decrease the burden of herpes zoster and pain associated with post-herpetic neuralgia. Despite the availability of a vaccine, there is a need for new antiviral agents. Current drugs approved for the treatment of VZV infections include nucleoside analogs that target the viral DNA polymerase and depend on the viral thymidine kinase. Novel anti-VZV drugs have recently been evaluated in clinical trials, including the bicyclic nucleoside analog FV-100, the helicase-primase inhibitor ASP2151 and valomaciclovir (prodrug of the acyclic guanosine derivative H2G). EXPERT OPINION: New anti-VZV drugs should be as safe as and more effective than acyclovir and its prodrug valacyclovir (current gold standard for the treatment of VZV).     

Emerging drugs for varicella-zoster virus infections

Introduction: Varicella-zoster virus (VZV) is the etiological agent of two distinct diseases, varicella (chickenpox) and shingles (herpes zoster). Chickenpox occurs following primary infection, while herpes zoster (usually associated with ageing and immunosuppression) is the consequence of reactivation of the latent virus. Post-herpetic neuralgia is the major complication of shingles.

Areas covered: This review will discuss vaccination strategies and the current status of antivirals against VZV. A live attenuated vaccine, Varivax, is available for pediatric varicella while Zostavax was developed to boost VZV-specific cell-mediated immunity in adults older than 60 years and, via this mechanism, to decrease the burden of herpes zoster and pain associated with post-herpetic neuralgia. Despite the availability of a vaccine, there is a need for new antiviral agents. Current drugs approved for the treatment of VZV infections include nucleoside analogs that target the viral DNA polymerase and depend on the viral thymidine kinase. Novel anti-VZV drugs have recently been evaluated in clinical trials, including the bicyclic nucleoside analog FV-100, the helicase–primase inhibitor ASP2151 and valomaciclovir (prodrug of the acyclic guanosine derivative H2G).

Expert opinion: New anti-VZV drugs should be as safe as and more effective than acyclovir and its prodrug valacyclovir (current gold standard for the treatment of VZV).     

临床药师参与1例带状疱疹后神经痛治疗方案分析

带状疱疹后神经痛(postherpetic neuralgia,PHN)为带状疱疹皮疹愈合后由病毒侵入神经所诱发的神经病理性疼痛,是临床中该疾病治疗最常发生且难以控制的并发症.本文中,临床药师对1例带状疱疹后神经痛患者的治疗方案进行分析,从药物使用、联用的角度讨论治疗方案的合理性,体现了临床药师在指导临床诊疗过程中的重...     

The incidence of recurrent herpes simplex and herpes zoster infection during treatment with arsenic trioxide

We report the incidence of varicella zoster virus (VZV) and herpes simplex virus (HSV) infection in patients with multiple myeloma and colon cancer who were treated with arsenic trioxide for their disease. In this report, we discuss the effects of arsenic on immune system, and suggest arsenic compounds as a possible predisposing factor for viral reactivation in these patients.     

Current pharmacological approaches to the therapy of varicella zoster virus infections: a guide to treatment

Varicella zoster virus (VZV), a member of the herpesvirus family, is responsible for both primary (varicella, chickenpox) as well as reactivation (zoster, shingles) infections. In immunocompetent patients, the course of varicella is generally benign. For varicella zoster, post-herpetic neuralgia is the most common complication. In immunocompromised patients (particularly those with AIDS), transplant recipients and cancer patients, VZV infections can be life-threatening. For these patients and also for immunocompetent patients at risk such as pregnant women or premature infants, the current treatment of choice is based on either intravenous or oral aciclovir (acyclovir). The low oral bioavailability of aciclovir, as well as the emergence of drug-resistant virus strains, have stimulated efforts towards the development of new compounds for the treatment of individuals with VZV infections. Among these new compounds, penciclovir, its oral prodrug form famciclovir and the oral pro-drug form of aciclovir (valaciclovir), rank among the most promising. As with aciclovir itself, all of these drugs are dependent on the virus-encoded thymidine kinase (TK) for their intracellular activation (phosphorylation), and, upon conversion to their triphosphate form, they act as inhibitors/alternative substrate of the viral DNA polymerase. Therefore, cross-resistance to these drugs may be expected for those virus mutants that are TK-deficient and thus resistant to aciclovir. Other classes of nucleoside analogues dependent for their phosphorylation on the viral TK that have been pursued for the treatment of VZV infections include sorivudine, brivudine, fialuridine, fiacitabine and netivudine. Among oxetanocins, which are partially dependent on viral TK, lobucavir is now under clinical evaluation. Foscarnet, which does not require any previous metabolism to interact with the viral DNA polymerase, is used in the clinic when TK-deficient VZV mutants emerge during aciclovir treatment. TK-deficient mutants are also sensitive to the acyclic nucleoside phosphonates (i.e. [s]-1-[3-hydroxy-2-phosphonylmethoxypropyl]cytosine; HPMPC); these agents do not depend on the virus-encoded TK for their phosphorylation but depend on cellular enzymes for conversion to their diphosphoryl derivatives which then inhibit viral DNA synthesis. Vaccination for VZV has now come of age. It is recommended for healthy children, patients with leukaemia, and patients receiving immunosuppressive therapy or those with chronic diseases. The protection induced by the vaccine seems, to some extent, to include zoster and associated neuralgia. Passive immuniatin based on specific immunoglobulins does not effectively prevent VZV infection and is therefore restricted to high risk individuals (i.e. immunocompromised children and pregnant women).     

Post-herpetic neuralgia in older adults: evidence-based approaches to clinical management

Many individuals across the globe have been exposed to the varicella-zoster virus (VZV) that causes chickenpox. After chickenpox has resolved, the virus remains latent in the dorsal root ganglia where it can re-emerge later in life as herpes zoster, otherwise known as shingles. Herpes zoster is a transient disease characterised by a dermatomal rash that is usually associated with significant pain. Post-herpetic neuralgia (PHN) is the term used for the condition that exists if the pain persists after the rash has resolved. Advanced age and compromised cell-mediated immunity are significant risk factors for reactivation of herpes zoster and the subsequent development of PHN. Though the pathophysiology of PHN is unclear, studies suggest peripheral and central demyelination as well as neuronal destruction are involved. Both the vaccine against VZV (Varivax) and the newly released vaccine against herpes zoster (Zostavax) may lead to substantial reductions in morbidity from herpes zoster and PHN. In addition, current evidence suggests that multiple medications are effective in reducing the pain associated with PHN. These include tricyclic antidepressants, antiepileptics, opioids, NMDA receptor antagonists as well as topical lidocaine (lignocaine) and capsaicin. Reasonable evidence supports the use of intrathecal corticosteroids, but the potential for neurological sequelae should prompt caution with their application. Epidural corticosteroids have not been shown to provide effective analgesia for PHN. Sympathetic blockade may assist in treating the pain of herpes zoster or PHN. For intractable PHN pain, practitioners have performed delicate surgeries and attempted novel therapies. Although such therapies may help reduce pain, they have been associated with disappointing results, with up to 50% of patients failing to receive acceptable pain relief. Hence, it is likely that the most effective future treatment for this disease will focus on prevention of VZV infection and immunisation against herpes zoster infection with a novel vaccine.     

Molecular modeling and synthesis of inhibitors of herpes simplex virus type 1 uracil-DNA glycosylase.

We recently reported the properties of the first selective inhibitors of herpes simplex virus type 1 (HSV1) uracil-DNA glycosylase (UDG), an enzyme of DNA repair that has been proposed to be required for reactivation of the virus from latency. 6-(4-Octylanilino)uracil (octAU) was the most potent inhibitor among a series of 6-(4-alkylanilino)uracils, acting in the micromolar range and without effect against human UDG. A 28.5-kDa catalytic fragment of HSV1 UDG has been crystallized in the presence of uracil, and the structure was recently solved. We have used the coordinates of this structure in order to study interaction of our inhibitors with the enzyme, and a model of binding between octAU and UDG has been derived. Starting with the optimized model, the activity of several octAU analogues was predicted, and the values compared favorably with experimental results found for the synthetic compounds. Several hydrophilic derivatives were predicted and found to be active as UDG inhibitors. These compounds will be useful to determine if UDG, like the viral thymidine kinase, is required for reactivation of HSV1 from latency in nerve cells.     

Viral prophylaxis in organ transplant patients

Viral pathogens have emerged as the most important microbial agents having deleterious effects on solid organ transplant (SOT) recipients. Antiviral chemoprophylaxis involves the administration of medications to abort transmission of, avoid reactivation of, or prevent progression to disease from, active viral infection. Cytomegalovirus (CMV) is the major microbial pathogen having a negative effect on SOT recipients. CMV causes infectious disease syndromes, augments iatrogenic immunosuppression and is commonly associated with opportunistic superinfection. CMV has also been implicated in the pathogenesis of rejection. Chemoprophylactic regimens for CMV have included oral aciclovir (acyclovir) at medium and high doses, intravenous and oral ganciclovir, and the prodrugs valaciclovir (valacyclovir) and valganciclovir. CMV prophylactic strategies should be stratified, with the highest-risk patients receiving the most 'potent' prophylactic regimens. Herpes simplex virus (HSV) reactivation in SOT recipients is more frequent, may become more invasive, takes longer to heal, and has greater potential for dissemination to visceral organs than it does in the immunocompetent host. Prophylactic regimens for CMV are also effective chemoprophylaxis against HSV; in the absence of CMV prophylaxis, aciclovir, valaciclovir or famciclovir should be used as HSV prophylaxis in seropositive recipients. Primary varicella-zoster virus (VZV) after SOT is rare and most commonly seen in the paediatric transplant population because of VZV epidemiology. Zoster occurs in 5-15% of patients, usually after the sixth post-transplant month. Prophylactic regimens for zoster are neither practical nor cost effective after SOT because of the late onset of disease and low proportion of affected individuals. All SOT recipients should receive VZV immune globulin after contact with either varicella or zoster. Epstein-Barr virus has its most significant effect in SOT as the precipitating factor in the development of post-transplant lymphoproliferative disorders. Antiviral agents that could be effective are the same as those used for CMV, but indications for and effectiveness of prophylaxis are poorly established. Hepatitis B virus (HBV) and hepatitis C virus (HCV) are important pathogens in the SOT population as indications for transplantation. So-called 'prophylaxis' for recurrent HBV and HCV after liver transplantation is controversial, suppressive rather than preventive, and potentially lifelong. Influenza infection after SOT is acquired by person-to-person contact. During epidemic periods of influenza, transplant populations experience a relatively high frequency of infection, and influenza may affect immunosuppressed SOT recipients more adversely than immunocompetent individuals. Antiviral medications for prevention of influenza are administered as post-exposure prophylaxis to SOT recipients, in addition to yearly vaccine, in circumstances such as influenza epidemics and nosocomial outbreaks, and after exposure to a symptomatic individual during 'flu season'.     

Virus reactivation and intravenous immunoglobulin (IVIG) therapy of drug-induced hypersensitivity syndrome

Drug-induced hypersensitivity syndrome (DIHS) is a severe multi-organ system reaction caused by specific drugs. Many reports have revealed that human herpesvirus 6 (HHV-6) reactivation contributes to the development of DIHS. In addition, recent articles have shown that reactivation of other herpesviruses such as human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV), cytomegalovirus (CMV) might be also implicated in the development of DIHS. These observations suggest that not only HHV-6 but also other herpesvirses might reactivate from the latency and play an important role in the appearance of clinical manifestations of DIHS. Several patients with DIHS were treated with intravenous immunoglobulin (IVIG) in addition to systemic corticosteroids. The results have been encouraging although virus reactivation could not be suppressed. Although the pathomechanism of IVIG treatment in patients with DIHS remains unknown, the therapeutic effects of IVIG could be dependent, in part, on functional capabilities of anti-virus IgG contained in IVIG.