Acute ascending necrotizing myelitis in Okinawa caused by herpes simplex virus type 2

Summary A case of rapidly progressing ascending myelitis was necropsied. Necrosis was present throughout the whole length of the spinal cord and involved both the grey and white matter randomly. The perivascular lymphocytic infiltration in the spinal cord in the present case was more pronounced than that in the previously reported two cases of necrotizing myelopathy associated with malignancy. Using immunoperoxidase staining the presence of herpes simplex virus type 2 (HSV 2) antigen was demonstrated. Electron microscopic examinations revealed large numbers of HSV particles in the spinal cord. HSV 2 may be a common aetiological agent of necrotizing myelopathy and myelitis in Okinawa, an HSV 2 endemic area. In the present case, the necrosis was mainly found in the spinal cord but was also observed, to a very limited extent, in the brain.     

Community-based study on seroprevalence of herpes simplex virus type 2 infection in New Delhi

PURPOSE: To determine the seroprevalence of herpes simplex virus type 2 (HSV-2) in two urban communities in Delhi and to correlate the presence of HSV-2 seroprevalence with sociodemographic profile, risk factors and presence of other reproductive tract infections (RTIs). METHODS: Men and women aged between 15-49 years from an urban slum and an urban middle class colony were invited to participate in the study. They provided interview information; blood for HSV-2, HIV and syphilis serology; first void urine specimens for diagnosis of Neisseria gonorrhoeae and Chlamydia trachomatis infection; and genital specimens for diagnosis of bacterial vaginosis, vaginal candidiasis and trichomoniasis. RESULTS: The prevalence of HSV-2 seropositivity was found to be 7 and 8.6% in men and women, respectively. HSV-2 seropositivity was found to be significantly associated with urban middle class community and older age. No statistically significant correlation was found between HSV-2 seropositivity and other laboratory-confirmed RTIs. CONCLUSIONS: The findings of our study indicate a relatively low prevalence of HSV-2 seropositivity and other sexually transmitted infections in the two communities that were studied.     

Relationship between cervical disease and infection with human papillomavirus types 16 and 18, and herpes simplex virus 1 and 2

Persistent infection with high‐risk HPV, particularly Type HPV 16 and 18, is necessary in the development of cervical cancer, but apart from HPV infection, other causative factors of most cervical cancers remain unknown. The aim of this study was to determine the prevalence of HPV 16 and HPV 18 and HSV 1 and HSV 2 in cervical samples, and to assess the role of HSVs in cervical carcinogenesis. Two hundred thirty‐three healthy controls and 567 cases (333 of cervicitis, 210 of cervical intraepithelial neoplasia, and 24 of squamous cell carcinoma) in cervical exfoliative cells were tested for HPV 16, HPV 18, HSV 1, and HSV 2 DNA using the triplex real‐time polymerase chain reaction method. In contrast to healthy women, positive rate of HPV is related significantly to cervical lesions (odds ratios (ORs) = 4.1, P < 0.01 for cervical intraepithelial neoplasia; ORs = 24.9, P < 0.01 for squamous cell carcinoma), but not cervicitis (ORs = 2.3, P > 0.05). HSV 2 prevalence in cervical intraepithelial neoplasia and squamous cell carcinoma was higher than in healthy women (ORs = 4.9, P < 0.05 for cervical intraepithelial neoplasia; ORs = 4.7, P < 0.05 for squamous cell carcinoma). HSV 2 coinfection with HPV in cervical intraepithelial neoplasia and squamous cell carcinoma was strongly higher than in healthy women (ORs = 34.2, P < 0.01 for cervical intraepithelial neoplasia; ORs = 61.1, P < 0.01 for squamous cell carcinoma). The obtained results indicated that the presence of HPV is associated closely with cervical cancer, and that HSV 2 infection or co‐infection with HPV might be involved in cervical cancer development, while HSV 1 might not be involved. J. Med. Virol. 84:1920–1927, 2012. © 2012 Wiley Periodicals, Inc.     

Application of shRNA-containing herpes simplex virus type 1 (HSV-1)-based gene therapy for HSV-2-induced genital herpes

HSV-1-based vectors have been widely used to achieve targeted delivery of genes into the nervous system. In the current study, we aim to use shRNA-containing HSV-1-based gene delivery system for the therapy of HSV-2 infection. Guinea pigs were infected intravaginally with HSV-2 and scored daily for 100 days for the severity of vaginal disease. HSV-2 shRNA-containing HSV-1 was applied intravaginally daily between 8 and 14 days after HSV-2 challenge. Delivery of HSV-2 shRNA-containing HSV-1 had no effect on the onset of disease and acute virus shedding in animals, but resulted in a significant reduction in both the cumulative recurrent lesion days and the number of days with recurrent disease. Around half of the animals in the HSV-2 shRNA group did not develop recurrent disease 100 days post HSV-2 infection. In conclusion, HSV-2 shRNA-containing HSV-1 particles are effective in reducing the recurrence of genital herpes caused by HSV-2.     

Herpes simplex virus seroprevalence and seroconversion among active duty US air force members with HIV infection

BackgroundHerpes simplex virus (HSV) infection is associated with an increased risk of both HIV transmission and acquisition. We evaluated longitudinal HSV serology and sexually transmitted infections (STIs) among active duty US Air Force (USAF) members with HIV infection.MethodsUSAF members diagnosed with HIV between 1996 and 2012 were included and divided into 2 groups: 1996–2004 (n = 131) and 2005–2012 (n = 266). HSV-1 and -2 serology was evaluated at HIV diagnosis. Longitudinal HSV-1 and -2 serology and ICD-9 codes for HSV and non-HSV STIs were also examined for those with ≥1 year of follow-up.ResultsPatients were most commonly Caucasian (44.2%) or African American (43.4%) men with a median age of 28 years at HIV diagnosis. HSV-2 seroprevalence at HIV diagnosis decreased from the period of 1996–2004 (48.8%) to 2005–2012 (30.1%; P < 0.01). Odds of HSV-2 seropositivity was significantly greater for non-Caucasians (OR 2.19, 95% CI 1.33–3.60) and for HIV diagnosis between 1996 and 2004 (OR 2.06, 95% CI 1.29–3.27), with a trend observed for those age >30 years at HIV diagnosis (OR 1.73, 95% CI 0.94–3.18). A total of 81 (20.4%) patients developed STIs by ICD-9 codes, including 24 (6.1%) new genital herpes diagnoses, during a median follow-up of 4.6 years. HSV-2 seroconversion occurred in 33 of 253 (13.0%) with an incidence rate of 5.07 per 100 person-years (95% CI 4.76–5.37).ConclusionAlthough HSV-2 seroprevalence at HIV diagnosis decreased over time, high-risk sexual behaviors were ongoing as evidenced by the high proportion of new STI diagnoses and HSV-2 seroconversions. Continued education to reduce risk behaviors is warranted to prevent acquisition and transmission of STIs in HIV-infected persons.     

细胞周期蛋白依赖性激酶2活性与单纯疱疹病毒复制关系的研究

目的 探讨细胞周期蛋白依赖性激酶(CDK)2在单纯疱疹病毒(HSV)复制中的作用. 方法 以能够诱导表达CDK2显性负突变体致使CDK2功能缺陷的人结肠癌细胞株HT29Tet-Ondn-CDK2为材料,用免疫共沉淀及放射自显影法测定HSV感染后不同时间CDK2活性,并进行HSV的增殖动力学分析. 结果 HSV感染6h后CDK2活性被诱导,9h达到最大;一步生长曲线结果表明在CDK2活性被诱导前HSV处于静止状态,CDK2活性被诱导后HSV即进入快速的生长复制阶段. 结论 CDK2是HSV复制所必需的,HSV通过诱导宿主细胞CDK2活性而促进本身的复制.     

Epidemiology and risk factors for human papillomavirus infection in a diverse sample of low-income young women

BackgroundTwo HPV vaccines prevent infection with HPV-16 and HPV-18, high-risk (cancer-associated) HPV types which together cause approximately 70% of cervical cancers; one vaccine also prevents HPV-6 and HPV-11, which together cause approximately 90% of anogenital warts. Defining type-specific HPV epidemiology in sexually experienced women will help estimate the potential clinical benefits of vaccinating this population.ObjectivesTo examine HPV epidemiology in a diverse sample of sexually experienced women, and to determine factors associated with high-risk HPV and vaccine-type HPV (HPV-6, HPV-11, HPV-16 and HPV-18).Study designCross-sectional study of 13–26-year-old women (N = 409) who completed a questionnaire and provided a cervicovaginal swab. Swabs were genotyped for HPV using PCR amplification. Logistic regression models were used to determine whether participant characteristics, knowledge, and behaviors were associated with high-risk and vaccine-type HPV.ResultsMost women (68.4%) were positive for ≥1 HPV type, 59.5% were positive for ≥1 high-risk type, 33.1% were positive for ≥1 vaccine-type HPV, and 3.5% were positive for both HPV-16 and HPV-18: none was positive for all four vaccine types. In adjusted logistic regression models, Black race (OR 2.03, 95% CI 1.21–3.41) and lifetime number of male sexual partners (OR 4.79, 95% CI 2.04–11.23 for ≥10 partner vs. ≤1 partner) were independently associated with high-risk HPV infection.ConclusionsHPV prevalence was very high in this sample of sexually active young women, but <5% were positive for both HPV-16 and HPV-18, suggesting that vaccination could be beneficial for many individual women who are sexually experienced.     

聚合酶链反应酶谱分型检测宫颈癌中人乳头瘤病毒 …

目的 探讨人乳头瘤病毒（ＨＰＶ）和单纯疱疹病毒（ＨＳＶ）等对宫颈癌的病因学作用。方法 应用聚合酶链反应（ＰＣＲ）－核酸内切酶分型检测宫颈癌活检组织中ＨＰＶ－ＤＮＡ和ＨＳＶ－ＤＮＡ基因,以正常宫颈组织作对照。结果 在宫颈癌活检细胞中ＨＰＶ－１６,１８型和ＨＳＶ－２型阳性率分别为３８．９％和３４．６％,与正常妇女宫颈组织阳性率均为３．２％比较,差异均有非常显著意义（Ｐ〈０．００１）。结论 ＨＰＶ－１６     

Herpes simplex virus type 2 and heterosexual spread of human immunodeficiency virus infection in developing countries: hypotheses and research priorities

Herpes simplex virus type 2 (HSV-2) infection is almost always sexually transmitted, and causes genital ulceration. Significant progress in our understanding of HSV infection has occurred over the last decade, in part related to the development of accurate and sensitive laboratory tests to study HSV-2. The application of PCR and type-specific serology to individual cases and in population-based studies has enabled the identification of a potentially important role for HSV-2 infection as a cofactor in the sexual transmission of HIV. This is a particular issue in developing countries. This review describes the epidemiology of HSV-2 infection in the HIV era, the hypotheses regarding HSV–HIV interactions, and research priorities for the developing world.     

Analysis of varicella-zoster virus and herpes simplex virus in various clinical samples by the use of different PCR assays

Rapid and reliable detection of varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) and -2 (HSV-2) is of clinical significance in immunocompromised patients and patients with infections of the central nervous system. This paper describes the detection of VZV and HSV using the commercially available Affigene^® VZV and Affigene^® HSV 1/2 tracer kits in comparison to “in-house” polymerase chain reaction (PCR) assays. For sample preparation, Qiagen (Hilden, Germany) and Affigene^® (Cepheid AB, Bromma, Sweden) DNA extraction kits were used. 175 samples were analyzed for VZV and 352 samples for HSV-1 and -2. Generally more positive results were obtained using the Affigene^® assays compared to the “in-house” methods independent of the DNA preparation method used. There were significant differences in sensitivity between the Affigene^® HSV 1/2 tracer and the “in-house” PCR assays for the detection of both HSV-1 and -2 in cerebrospinal fluid and vesicle/skin swabs. The Affigene^® HSV 1/2 and VZV tracers are very sensitive assays for detection of VZV and HSV. A wide variety of clinical samples can be examined in combination with either the Qiagen or the Affigene^® DNA extraction kits for preparation.     

Tubular structures in the cervix of mice experimentally infected with herpes simplex virus type 2

Experimental infection of the C3H/N mouse genital tract was demonstrated after intravaginal inoculation with herpes simplex virus type 2 (HSV-2). About 75% of the infected animals died by Day 7, and 75% of the surviving animals had severe vaginitis or neurological signs on Day 7. Titers of the virus recovered from vaginal secretions of infected animals reached a maximum on Day 2 and gradually decreased until Day 7. On the other hand, under the electron microscope, virus particles and tubular structures could be found in the nuclei of infected cells of the cervix in the 1st, 2nd and 4th days after infection. All cases in which virus particles could be found in the nuclei of infected cells were also positive for tubular structures and vice versa. These observations indicate that in situ diagnosis of HSV-2 infection can be made in the mouse model. The same method would be applicable for the diagnosis of human HSV-2 infection.     

Effects of S-acetylglutathione in cell and animal model of herpes simplex virus type 1 infection

Intracellular glutathione (GSH) plays an important regulatory role in the host response to viral infections. Replenishment of intracellular GSH is a desirable yet challenging goal, since systemic GSH supplementation is rather inefficient due to a short half-life of GSH in blood plasma. Further, GSH is not taken up by cells directly, but needs to be broken down into amino acids and resynthesized to GSH intracellularly, this process often being impaired during viral infections. These obstacles may be overcome by a novel glutathione derivative S-acetylglutathione (S-GSH), which is more stable in plasma and taken up directly by cells with subsequent conversion to GSH. In the present study, in vitro effects of supplementation with S-GSH or GSH on intracellular GSH levels, cell survival and replication of human herpes simplex virus type 1 (HSV-1) were studied in human foreskin fibroblasts. In addition, in vivo effects of supplementation with S-GSH or GSH on HSV-1-induced mortality were studied in hr/hr mice. In cell culture, viral infection resulted in a significant decrease of intracellular GSH levels. S-GSH efficiently and dose-dependently (5 and 10 mM tested) restored intracellular GSH, and this replenishment was more efficient than with GSH supplementation. In mice, S-GSH, but not GSH, significantly decreased HSV-1-induced mortality (P<0.05). The data suggest that S-GSH is a suitable antiviral agent against HSV-1 both in vitro and in vivo, indicating that this drug may be of benefit in the adjunctive therapy of HSV-1 infections.     

Effect of herpes simplex virus on the DNA of human papillomavirus 18

Some types of human papillomaviruses (HPV) appear to be associated with carcinoma of the cervix or other tissues, but patients infected with HPV do not necessarily develop carcinoma. Some epidemiological studies of risk factors for cervical carcinoma have indicated the involvement of herpes simplex virus (HSV). To study the effect of HSV on the genome of HPV, total DNAs were extracted and analyzed after HeLa cells, or A431 cells, transiently transfected with HPV18 DNA, were infected with HSV-1 or -2 for 24 hours. In HeLa cells, integrated HPV18 DNA was amplified almost threefold. In A431 cells, HPV 18 DNA fragments, sensitive to the restriction enzyme Mbo I, indicated newly replicated DNA. Replication intermediates were detected when the DNA was resolved by two-dimensional gel electrophoresis. This study showed that HSV caused some amplification of HPV and indicated the possibility of HSV involved in the integration and amplification of HPV in host cells. J. Med. Virol. 53:4–12, 1997. © 1997 Wiley-Liss, Inc.     

Identification of structural protein-protein interactions of herpes simplex virus type 1

In this study we have defined protein-protein interactions between the structural proteins of herpes simplex virus type 1 (HSV-1) using a LexA yeast two-hybrid system. The majority of the capsid, tegument and envelope proteins of HSV-1 were screened in a matrix approach. A total of 40 binary interactions were detected including 9 out of 10 previously identified tegument-tegument interactions (Vittone, V., Diefenbach, E., Triffett, D., Douglas, M.W., Cunningham, A.L., and Diefenbach, R.J., 2005. Determination of interactions between tegument proteins of herpes simplex virus type 1. J. Virol. 79, 9566-9571). A total of 12 interactions involving the capsid protein pUL35 (VP26) and 11 interactions involving the tegument protein pUL46 (VP11/12) were identified. The most significant novel interactions detected in this study, which are likely to play a role in viral assembly, include pUL35-pUL37 (capsid-tegument), pUL46-pUL37 (tegument-tegument) and pUL49 (VP22)-pUS9 (tegument-envelope). This information will provide further insights into the pathways of HSV-1 assembly and the identified interactions are potential targets for new antiviral drugs.     

联合靶向小干扰RNA对疱疹病毒2感染的体外抑制作用

目的 探讨联合靶向特异性小干扰RNA(siRNA)对疱疹病毒(HSV)2的体外特异抑制作用.方法 将体外合成的靶向HSV-2编码包膜糖蛋白gB的UL27.2基因、靶向DNA结合蛋白UL29.2基因的siRNA和该两种联合靶向特异性siRNA制剂,共转染Vero细胞并感染HSV-2,观察靶基因的表达情况、Vero细胞病变、空斑减数实验和子代病毒滴度并进行各组间比较:结果特异性UL27.2siRNA、UL29.2 siRNA和联合siRNA转染Vero细胞后,均能不同程度抑制各HSV-2临床株感染所导致的细胞病变,对病毒增殖抑制率分别为63.9%、86.7%和93.3%.实时定量PCR检测各组siRNA分别对UL27.2和UL29.2两个基因的表达,结果显示UL27.2 siRNA和UL29.2 siRNA对各自的靶向基因均有抑制,而联合靶向siRNA制剂对两个基因的抑制率最高.结论 联合靶向特异性siRNA制剂能有效抑制HSV-2的感染和复制.     

表达hIFNα-2b基因重组乳杆菌治疗HSV-2感染的研究

目的 探讨表达人干扰素α-2b的重组乳杆菌应用于阴道HSV-2感染的治疗作用。方法 建立阴道感染HSV-2的小鼠模型，使用重组菌菌液于感染前24h进行预防，或感染后48h进行治疗，记录病损程度并检测小鼠阴道分泌物中HSV-2滴度。结果使用重组菌预防或治疗的小鼠症状轻且病程缩短，病灶中病毒滴度下降很快。结论表达IFNα-2b的重组乳杆菌具有较强的局部抗病毒作用，可用于预防及治疗由HSV-2感染引起的生殖器疱疹。     

巢式PCR检测龈下菌斑中HCMV、EBV、HSV-1与慢性牙周炎活动性的关系

目的　建立临床检测龈下菌斑标本中人巨细胞病毒 (HCMV)、Epstein Barr病毒 (EBV)、单纯疱疹病毒 1型 (HSV 1 )巢式PCR方法 ,研究这 3种病毒与慢性牙周炎活动性的关系。方法　收集6 2例慢性牙周炎患者 (男性 2 7例、女性 35例 ,平均年龄 5 3岁 )的牙周炎活动部位、牙周炎静止部位的龈下菌斑 ,提取DNA后使用巢式PCR检测HCMV、EBV、HSV 1 ,比较分析其在同一病人不同部位的检出率。结果　牙周炎活动部位的HCMV检出率为 38.7%,EBV的检出率为 5 8%,HSV 1的检出率为30 .6 %,两种以上病毒合并感染的检出率为 4 0 .3%;牙周炎静止部位的HCMV检出率为 1 4 .5 %,EBV为 2 2 .6 %,HSV 1为 1 1 .3%,两种以上病毒合并感染的检出率为 1 1 .3%。这 3种病毒及其合并感染在牙周炎活动部位的检出率均高于牙周炎静止部位 ,差异有统计学意义 (P <0 .0 5 )。结论　提示HC MV、EBV、HSV 1与慢性牙周炎的活动性相关。     

Immunization with a replication-defective herpes simplex virus 2 mutant reduces herpes simplex virus 1 infection and prevents ocular disease

Ocular infections with herpes simplex virus 1 can lead to corneal scarring and blindness, with herpes keratitis being the major infectious cause of blindness. There is currently no clinically approved vaccine and nearly all developmental vaccines are targeted against HSV-2 and genital herpes. We tested the ability of an HSV-2 replication-defective virus, a genital herpes vaccine candidate, to protect against HSV-1 corneal infection. Immunization with HSV-2 dl5-29 reduced viral replication in the cornea, prevented ocular disease and reduced latent infection by the HSV-1 strain. Therefore, this HSV-2 replication-defective mutant strain may have applications for prevention of herpes keratitis and genital herpes due to HSV-1 infection.     

Prevalence of active infection by herpes simplex virus type 2 in patients with high-risk human papillomavirus infection: A cross-sectional study

The aim is to determine the prevalence of active infection by herpes simplex virus type 2 (HSV-2) among Mexican women with high-risk human papillomavirus (HR-HPV) cervical infection, recruited from public gynecology and colposcopy services. In a cross-sectional study, HSV-2 antibodies, HSV-2 DNA, and HR-HPV DNA were quantified. Significant differences in HSV-2 seroprevalence and HSV-2 active infection rates were found between negative and positive HR-HPV cases. HSV-2 seroprevalence was 28.15% and 16.1% (P = .0001), while HSV-2 active infection rates were 6.83% and 0.62% (P = .001) for positive and negative HR-HPV groups, respectively. The risk of HSV-2 seropositivity was 1.7 times greater for HR-HPV-positive cases (P = .02). Similarly, HR-HPV-positive cases were nine times more likely to have an HSV-2 active infection than HR-HPV-negative cases (P = .03). High HSV-2/h-HPV coinfection rates were observed among women recruited from public gynecology and colposcopy services. The main factors related to an HSV-2 active infection are a history of risky sexual behavior and HR-HPV infection. The prevalence of HSV-2 active infection among positive HR-HPV subjects indicate that these infections constitute an important group of STIs in Mexico.     

人乳头瘤病毒16型中国株L1基因的体外真核表达

目的 构建人类乳头瘤病毒16型(HPV16)中国株晚期基因L1的真核表达系统.方法 将HPV16中国株L1基因从pCR2.1/HPV16L1定向亚克隆至pTacer-CMV载体,构建重组质粒pTaeer-CMV/HPV16L1,将重组质粒用脂质体转染N1H3T3、HeLa细胞,用透射电镜、SDS-PAGE、蛋白印迹等方法观察HPV16 L1蛋白的表达.结果 NIH3T3、HeLa细胞经pTacer-CMV/HPV16L1转染后,SDS-PAGE、蛋白印迹等实验显示可表达HPV16 L1蛋白,电镜下可见病毒样颗粒(VLP).结论 pTacer-CMV/HPV16L1构建成功,可在体外表达HPV16中国株L1蛋白.