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  • 1.

    【2hr】Constitutive and Inducible Innate Responses in Cells Infected by HSV-1-Derived Amplicon Vectors

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    机译 HSV-1衍生扩增子载体感染细胞的本构和诱导性先天反应
    摘要：Amplicons are helper-dependent herpes simplex virus type 1 (HSV-1)-based vectors that can deliver very large foreign DNA sequences and, as such, are good candidates both for gene delivery and vaccine development. However, many studies have shown that innate constitutive or induced cellular responses, elicited or activated by the entry of HSV-1 particles, can play a significant role in the control of transgenic expression and in the induction of inflammatory responses. Moreover, transgene expression from helper-free amplicon stocks is often weak and transient, depending on the particular type of infected cells, suggesting that cellular responses could be also responsible for the silencing of amplicon-mediated transgene expression. This review summarizes the current experimental evidence underlying these latter concepts, focusing on the impact on transgene expression of very-early interactions between amplicon particles and the infected cells, and speculates on possible ways to counteract the cellular protective mechanisms, thus allowing stable transgene expression without enhancement of vector toxicity.
  • 2.

    【2hr】Herpesvirus Vectors for Therapy of Brain Tumors

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    机译 疱疹病毒载体治疗脑肿瘤
    摘要：Genetically modified, conditionally-replicating Herpes Simplex Virus Type 1 (HSV-1) vectors for the treatment of malignant glioma have provided encouraging results in the handful of Phase I and Phase II clinical trials conducted to date. In recent years, a number of new strategies have been developed to improve anti-tumor activity of these attenuated vectors, through either introduction of foreign gene inserts to enhance tumor killing through a variety of mechanisms, or through combination with existing treatment regimens, including radiation and/or chemotherapeutics. Another promising new approach has been the engineering of novel oncolytic HSV vectors that retain wildtype replication, but are targeted to tumor cells through a variety of mechanisms. This review summarizes the latest advances in herpesvirus-mediated oncolytic therapies from both preclinical results and clinical trials with oncolytic HSV vectors in patients, and their implication for design of future trials.
  • 3.

    【2hr】Herpes Simplex Virus Type 1/Adeno-Associated Virus Hybrid Vectors

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    机译 单纯疱疹病毒1 /腺相关病毒杂种载体
    摘要：Herpes simplex virus type 1 (HSV-1) amplicons can accommodate foreign DNA of any size up to 150 kbp and, therefore, allow extensive combinations of genetic elements. Genomic sequences as well as cDNA, large transcriptional regulatory sequences for cell type-specific expression, multiple transgenes, and genetic elements from other viruses to create hybrid vectors may be inserted in a modular fashion. Hybrid amplicons use genetic elements from HSV-1 that allow replication and packaging of the vector DNA into HSV-1 virions, and genetic elements from other viruses that either direct integration of transgene sequences into the host genome or allow episomal maintenance of the vector. Thus, the advantages of the HSV-1 amplicon system, including large transgene capacity, broad host range, strong nuclear localization, and availability of helper virus-free packaging systems are retained and combined with those of heterologous viral elements that confer genetic stability to the vector DNA. Adeno-associated virus (AAV) has the unique capability of integrating its genome into a specific site, designated AAVS1, on human chromosome 19. The AAV rep gene and the inverted terminal repeats (ITRs) that flank the AAV genome are sufficient for this process. HSV-1 amplicons have thus been designed that contain the rep gene and a transgene cassette flanked by AAV ITRs. These HSV/AAV hybrid vectors direct site-specific integration of transgene sequences into AAVS1 and support long-term transgene expression.
  • 4.

    【2hr】HSV Recombinant Vectors for Gene Therapy

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    机译 用于基因治疗的HSV重组载体
    摘要：The very deep knowledge acquired on the genetics and molecular biology of herpes simplex virus (HSV), has allowed the development of potential replication-competent and replication-defective vectors for several applications in human healthcare. These include delivery and expression of human genes to cells of the nervous systems, selective destruction of cancer cells, prophylaxis against infection with HSV or other infectious diseases, and targeted infection to specific tissues or organs. Replication-defective recombinant vectors are non-toxic gene transfer tools that preserve most of the neurotropic features of wild type HSV-1, particularly the ability to express genes after having established latent infections, and are thus proficient candidates for therapeutic gene transfer settings in neurons. A replication-defective HSV vector for the treatment of pain has recently entered in phase 1 clinical trial. Replication-competent (oncolytic) vectors are becoming a suitable and powerful tool to eradicate brain tumours due to their ability to replicate and spread only within the tumour mass, and have reached phase II/III clinical trials in some cases. The progress in understanding the host immune response induced by the vector is also improving the use of HSV as a vaccine vector against both HSV infection and other pathogens. This review briefly summarizes the obstacle encountered in the delivery of HSV vectors and examines the various strategies developed or proposed to overcome such challenges.
  • 5.

    【2hr】CXCR4 Tropic HIV-1 gp120 Inhibition of SDF-1α-Induced Chemotaxis Requires Lck and is Associated with Cofilin Phosphorylation

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    机译 CXCR4热带HIV-1 gp120抑制SDF-1α诱导的趋化性需要Lck，并与Cofilin磷酸化相关
    摘要：Objective:HIV gp120 is a pleiotropic protein present in the plasma and tissues of HIV-infected patients, which affects a variety of homeostatic functions. In this report, we examine the mechanism of how gp120 blocks CD4 T cells from migrating towards SDF-1α.
  • 6.

    【2hr】Distribution of Human Papillomavirus Genotypes in Sardinian Patients with Oral Squamous Cell Carcinoma

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    机译 人乳头瘤病毒基因型在撒丁岛口腔鳞状细胞癌患者中的分布
    摘要：Human papillomaviruses (HPVs) seem to play an important role in the pathogenesis of gynecological carcinomas and in head and neck carcinomas. The aim of this study was to detect and genotype HPVs in fresh oral squamous cell carcinoma (OSCC) from a Sardinian population, and to determine whether HPV presence was significantly associated with the development of OSCC.The oral mucosa tissues were obtained from 120 samples (68 OSCC and 52 control samples) taken from a Sardinian population seen at the Dental Clinic of the Department of Surgery and Odontostomatological Sciences, University of Cagliari (Italy) and the “ Ospedale SS Trinità”, Cagliari (A.S.L. 8) between 2007 and 2008. PCR was used for the detection of HPV DNA and the genotype was determined by DNA sequencing. The frequency of HPV infection was evaluated in relation to age, sex, smoking and alcohol use. Statistical analysis was performed using the SPSS 11.5 software.The results showed the presence of HPV-DNA in 60.3% of OSCC with HPV-16 (51.2%) being the most frequent genotype. In these Sardinian OSCC patients, HPV-DNA was detected more in males (65.8%) than in females (34.1%) while controls show a 0% of HPV presence. HPV positive was highly associated with OSCC among subjects with a history of heavy tobacco and alcohol use and among those with no such history.A greater frequency of high risk HPV presence was observed in patients with OSCC compared to health control patients. In addition these results suggested that oral HPV presence could be associated in OSCC subjects. Our results need more analyses to detect the HPV-DNA integration into tumoral cells.
  • 7.

    【2hr】Comparison of the DiagCor GenoFlow Human Papillomavirus Array Test and Roche Linear Array HPV Genotyping Test

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    机译 DiagCor GenoFlow人乳头瘤病毒阵列试验与Roche线性阵列HPV基因分型试验的比较
    摘要：Persistent infection of high-risk (HR) human papillomavirus (HPV) infection has been widely associated with cervical cancer. Monitoring HPV infection is therefore an important step against cervical cancer development. The DiagCor GenoFlow Human Papillomavirus Array Test (GenoFlow) is a novel HPV test based on PCR and “Flow-through” hybridization that can identify 33 HPV subtypes in 3 hours. In the present study, the GenoFlow Test was evaluated by comparing the genotyping results of 100 samples with Roche Linear Array HPV Genotyping Test (LA). The tests showed good agreement in detection of HPV-positive samples (concordance rate=95%, Cohen’s Kappa=0.896), with good agreement in detection of HR HPVs (Cohen’s Kappa=0.876). The GenoFlow Test showed high sensitivity (95%), high specificity (95%), low false positive rate (3.33%) and low false negative rate (7.50%). In conclusion, the novel GenoFlow Test showed comparable clinical performance to LA test, and offers advantages of reduction in turnaround time and manpower.
  • 8.

    【2hr】Editorial

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    机译 社论
    • 作者：Maria G Cusi
    • 刊名：The Open Virology Journal
    • 2010年第期
    摘要：
  • 9.

    【2hr】Herpesvirus Vectors in Gene Therapy

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    机译 疱疹病毒载体的基因治疗
    • 作者：Veijo Hukkanen
    • 刊名：The Open Virology Journal
    • 2010年第期
    摘要：
  • 10.

    【2hr】The Evolution of Viruses in Multi-Host Fitness Landscapes

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    机译 多宿主健身环境中病毒的演变
    摘要：Provided that generalist viruses will have access to potentially unlimited hosts, the question is why most viruses specialize in few hosts. It has been suggested that selection should favor specialists because there are tradeoffs limiting the fitness of generalists in any of the alternative hosts or because evolution proceeds faster with narrower niches. Here we review experiments showing that virus adaptation to a specific host is often coupled with fitness losses in alternative ones. In most instances, mutations beneficial in one host are detrimental in another. This antagonistic pleiotropy should limit the range of adaptation and promote the evolution of specialization. However, when hosts fluctuate in time or space, selective pressures are different and generalist viruses may evolve as well.
  • 11.

    【2hr】A Microarray Based Approach for the Identification of Common Foodborne Viruses

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    机译 基于微阵列的常见食源性病毒鉴定方法
    摘要：An oligonucleotide array (microarray) incorporating 13,000 elements representing selected strains of hepatitis A virus (HAV), human coxsackieviruses A and B (CVA and CVB), genogroups I and II of Norovirus (NV), and human rotavirus (RV) gene segments 3,4,10, and 11 was designed based on the principle of tiling. Each oligonucleotide was 29 bases long, starting at every 5th base of every sequence, resulting in an overlap of 24 bases in two consecutive oligonucleotides. The applicability of the array for virus identification was examined using PCR amplified products from multiple HAV and CV strains. PCR products labeled with biotin were hybridized to the array, and the biotin was detected using a brief reaction with Cy3-labeled streptavidin, the array subjected to laser scanning, and the hybridization data plotted as fluorescence intensity against each oligonucleotide in the array. The combined signal intensities of all probes representing a particular strain of virus were calculated and plotted against all virus strains identified on a linear representation of the array. The profile of the total signal intensity identified the strain that is most likely represented in the amplified cDNA target. The results obtained with HAV and CV indicated that the hybridization profile thus generated can be used to identify closely related viral strains. This represents a significant improvement over current methods for virus identification using PCR amplification and amplicon sequencing.
  • 12.

    【2hr】CD4 T Cells Treated with gp120 Acquire a CD45R0+/CD45RA+ Phenotype

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    机译 用gp120处理的CD4 T细胞获得CD45R0 + / CD45RA +表型
    摘要：HIV-infected patients exhibit quantitative and qualitative defects in CD4 T cells, including having increased numbers of CD4+CD45R0+/CD45RA+ T cells, although it remains unclear how these cells arise. Here we demonstrate that gp120 treatment of activated but not resting primary human CD4 T cells decreases number of cells with single positive CD45R0+/CD45RA- effector memory phenotype while proportionally increasing the subset of cells with double positive CD45R0+/CD45RA+ mixed phenotype. We found that double positive CD45R0+/CD45RA+CD4 T cells preferentially undergo apoptosis while single positive CD45R0+/CD45RA- and CD45R0-/CD45RA+ do not. Blocking gp120-CD4 interaction with sCD4 or inhibition Lck activity reverses gp120 induced increase in double positive CD45R0+/CD45RA+CD4 T cells and subsequently diminishes the apoptosis of double positive CD45R0+/CD45RA+ cells. Altogether these data indicate that gp120 ligation of the CD4 receptor increases the number of double positive CD45R0+/CD45RA+ CD4 T cells which subsequently undergo apoptosis in a CD4 dependent manner.
  • 13.

    【2hr】Acute Gastroenteritis in a Pediatric Hospital in Rio de Janeiro in Pre- and Post-Rotavirus Vaccination Settings

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    机译 轮状病毒接种前后的里约热内卢一家儿科医院的急性胃肠炎
    摘要：A 4½-year hospital-based survey was conducted in Rio de Janeiro to determine baseline rates of gastroenteritis-related cases, hospitalizations, and deaths; to examine the prevalence of rotavirus strains causing admissions; and to assess the immediate impact of the nationwide rotavirus immunization program launched in March 2006. From August 2002 to May 2007, 14,473 (10.4%) of the 139,747 consultations had AGE as primary diagnosis, 491 (3.4%) children required hospitalization and two (0.4%) dehydrated children died. Gastroenteritis contribution to hospitalizations varied from ~2.3% in 2004 and 2006 to 6.4% in 2005, being roughly half of them rotavirus-related cases. A gradual decrease in rotavirus strain diversity was observed from 2002 to 2005 when a single G9P[8] prevailed until April 2006. Then only short profile G9P[4] and G2P[4] strains were detected. Gastroenteritis cases were distributed year-round in a trimodal pattern with major winter peaks. Local climate apparently affected the incidence of gastroenteritis: reduction in dry years (2004 and 2007) and explosive outbreaks caused by multiple agents during the heavy rainfalls and recurrent floods of the 2005-early 2006 period. Besides rotavirus, adenovirus and calicivirus were major gastroenteritis agents of these seemingly waterborne outbreaks. In conclusion, rotavirus vaccination impacted marginally, if at all, on the incidence of childhood gastroenteritis, as favorable results obtained by comparing data from the post-vaccine period to the preceding unusual 2005 year all but disappeared when comparing to previous pre-vaccination periods, and the shift towards G2P[4] rotavirus strains may be a global trend unrelated to vaccination.
  • 14.

    【2hr】Effect of Immunomodulating Adjuvant Dzherelo (Immunoxel) in HIV Infected Patients Receiving Standard Antiretroviral Therapy

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    机译 免疫调节佐佐洛（Immunoxel）对接受标准抗逆转录病毒疗法的HIV感染患者的影响
    摘要：Open-label, matched-case, comparative trial was conducted in 40 HIV-infected patients to evaluate the adjunct effect of Dzherelo (Immunoxel) on immune and viral parameters. Arm A (n=20) received anti-retroviral therapy (ART) consisting of zidovudine, lamivudine, and efavirenz and arm B (n=20) received ART with Dzherelo. After 2 months total T-lymphocytes increased in ART recipients from 664 to 819 cells/μl (P=0.06), whereas in Dzherelo recipients they rose from 595 to 785(P=0.03). The CD4 T-cells expanded by 57.3% (218 to 343; P=0.002) in the ART arm and by 93.5% (184 to 356; P=0.004) in the Dzherelo arm. The accrual in absolute and relative number of CD8+ lymphocytes in ART and in the Dzherelo recipients was 43.2% (2.7%) and 50.4% (-0.5%) respectively. The CD4/CD8 ratio in Dzherelo recipients increased from 1.495 to 1.940 (P=0.03) but insignificant in the control: 1.418 to 1.613 (P=0.14). Activated CD3+ HLADR+ T-cells increased from 209 to 264 (P=0.02) and from 161 to 348 (P=0.0007) in ART and Dzherelo recipients respectively. No changes in CD20+ B-lymphocytes were seen in the control, but in Dzherelo patients they declined from 509 to 333 (P=0.00008). The proportion of CD3- CD16+CD56+ NK cells was not affected by ART but addition of Dzherelo raised NK cells from 11.2% to 17.1% (P=0.0001). About three-quarters (14/19) of patients on ART displayed decrease in viral load (1718 to 1419 copies/ml; P=0.008), while 95% of patients on Dzherelo had a decrease (1793 to 1368; P=0.001). Dzherelo has a favorable effect on the immune status and viral burden when given as an immunomodulating adjunct to ART.
  • 15.

    【2hr】Oncoviruses and Pathogenic MicroRNAs in Humans

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    机译 人体中的癌病毒和致病性MicroRNA
    摘要：For disease prognosis, the functional significance of the oncoviral integration locus in oncogenesis has remained enigmatic. The locus encodes several transcripts without protein products, but microRNAs (miRNAs) have recently been identified from a common oncoviral integration locus. miRNA is an endogenous, non-coding small RNA by which gene expression is suppressed. Although miRNA genes, such as let-7 in the nematode, have orthologs among animals, the relationship between miRNAs and tumorigenesis or tumor suppression has been mainly discovered in several human cancers. On the contrary, this review clearly demonstrates the potential for human tumorigenesis of both miRNA genes from oncoviral integration sites and other cellular onco-microRNA genes, and we conclude that alteration of the miRNA profile of cells can be defined as tumorigenic or tumor suppressive. Thus, we explain here that virally-pathogenic miRNAs could also be partly responsible for oncogenesis or oncogene suppression to confirm’ the RNA wave’, with the miRNAs hypothesized as a mobile and functional genetic element.
  • 16.

    【2hr】Neutrophil Apoptosis During Viral Infections

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    机译 病毒感染中的中性粒细胞凋亡
    摘要：Apoptosis, or programmed cell death, is a highly conserved cellular suicide mechanism. Apoptosis is critical to the effective resolution of inflammation, particularly in regulating the lifespan of neutrophils. Neutrophils are key components of the first line of defense against microorganisms. Thus, subversion of this critical host defense mechanism by pathogens can contribute to susceptibility to severe and recurrent infections. In this review, we describe the molecular mechanisms involved in PMN death in relationship with viral infections.
  • 17.

    【2hr】Human Papillomavirus (HPV) Type Distribution in Females with Abnormal Cervical Cytology. A Correlation with Histological Study

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    机译 宫颈细胞学异常的女性中的人乳头瘤病毒（HPV）类型分布。与组织学研究的关系
    摘要：The aim of this study was to determine human papillomavirus (HPV) types distribution in cervical preneoplasic lesions in a Southern Spanish population and their relationship between HPV type and grade of histopathological abnormality. Finally, 232 cervical samples from 135 women with previous cytological abnormalities were included in this study. Colposcopy studies and biopsies were performed. Haematoxylin-eosin stained slides were observed and detection of HPV DNA in cervical swabs was carried out with use of a polymerase chain reaction and microarrays technology. The relationship between the presence of HPV infection and diagnostic variables was evaluated. HPV 16 was the most common type followed by HPV 58, 51, 33 and 31. However, the two HPV types targeted in the prophylactic vaccines such as HPV type 16 and 18 were detected in only 37 (21.2%) and 2 (1.1%) cases respectively. Thirty-three (18.9%) of samples were infected with multiple types, the majority of them with two types. In addition, during the follow-up of patients many changes in type distribution were observed. Several studies will be necessary in order to evaluate the HPV type distribution for therapeutically and prophylactic purposes such as vaccine treatment. Also, because of the differences obtained depending of use of various DNA technologies, the performance of some comparative studies of the different methods from detection of HPV would be advisable in a high population of patients and with the most homogeneous conditions possible.
  • 18.

    【2hr】Therapeutic Vaccines Against Human Papillomavirus and Cervical Cancer

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    机译 抗人乳头瘤病毒和宫颈癌的治疗性疫苗
    摘要：Cervical cancer and its precursor intra-epithelial lesions are linked to infection by a subset of so-called “highrisk” human papillomavirus types, which are estimated to infect nearly four hundred million women worldwide. Two prophylactic vaccines have been commercialized recently targeting HPV16 and 18, the most prevalent viral types found in cervical cancer, which operate through induction of capsid-specific neutralizing antibodies. However, in patients with persistent infection these vaccines have not been found to protect against progression to neoplasia. Attempts are being made to develop therapeutic vaccines targeting nonstructural early viral proteins. Among these, E6 and E7 are the preferred targets, since they are essential for induction and maintenance of the malignant phenotype and are constitutively expressed by the transformed epithelial cells. Here are reviewed the most relevant potential vaccines based on HPV early antigens that have shown efficacy in preclinical models and that are being tested in clinical studies, which should determine their therapeutic capacity for eradicating HPV-induced premalignant and malignant lesions and cure cervical cancer.
  • 19.

    【2hr】The Prognosis of Late Presenters in the Era of Highly Active Antiretroviral Therapy in Serbia

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    机译 塞尔维亚高效抗逆转录病毒疗法时代晚期呈报者的预后
    摘要：To examine the prognosis of patients who present with very advanced HIV-induced immunodeficiency, and their response to highly active antiretroviral therapy (HAART), a series of 101 treatment naïve patients from the Serbian cohort of HIV infected patients, who presented with a CD4 count of ≤ 50/µL before commencing HAART, was retrospectively analyzed and factors influencing response to HAART and survival investigated. After a mean of three years (range 1-9) of treatment with PI-based and/or NNRTI-based regimens, a favorable response was achieved in 54.5% of the patients, treatment failure occurred in 13.9%, while 31.7% had a dissociative immunological/virological response. The overall estimated survival was eight years. Achievement of undetectable viremia during treatment appeared life saving (OR = 42.5, 95% CI 7.1 – 251.9, P = 0.000, as was a rise in CD4 cell count to over 200/μL (OR = 6.4, 95% CI 1.2-31.8, P = 0.023). However, undetectable viremia was the single predictor of longer survival (OR = 42.5, 95% CI 7.1 – 251.9, P = 0.000), regardless of the level of immune reconstitution (log rank, P = 0.31). Late presenters had a high probability of developing the metabolic syndrome while on HAART, with a median time to hyperlipidemia and lypodystrophy of 5 and 6 years, respectively. We conclude that late presenters on HAART may have a good prognosis, a prerequisite for which is sustained undetectable viremia regardless of the immune recovery.
  • 20.

    【2hr】HIV Protease Cleavage of Procaspase 8 is Necessary for Death of HIV-Infected Cells

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    机译 HIV蛋白酶对Procaspase 8的裂解是HIV感染细胞死亡所必需的
    摘要：Numerous host and viral factors are capable of causing death of HIV infected cells, uninfected bystander cells, or both. We assessed the relevance of HIV protease in infected cell killing by mutating its obligate substrate for death, procaspase 8. VSV pseudotyped HIV infection of cells expressing WT caspase 8 resulted in apoptotic cell death and generation of the HIV protease specific cleavage product of procaspase 8, casp8p41. Conversely, both cell death and casp8p41 production were inhibited in cells expressing procaspase 8 engineered to be resistant to HIV protease cleavage. Lymph nodes from HIV-infected patients with ongoing viral replication also selectively expressed casp8p41, which colocalized with both infected and apoptotic cells. HIV protease cleavage of procaspase 8 appears to be a necessary event for infected cell killing, which is responsible for infected cell death within lymphoid tissues from HIV-infected patients.
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