Concentration of Herpesviruses

A method has been developed for the concentration of herpesviruses by negative pressure ultrafiltration through dialysis tubing. The procedure results in high titer concentrates of unaggregated, morphologically intact viral particles with a virtually quantitative recovery of infectivity.     

Herpesviruses and Chromosomal Integration

Herpesviruses are members of a diverse family of viruses that colonize all vertebrates from fish to mammals. Although more than one hundred herpesviruses exist, all are nearly identical architecturally, with a genome consisting of a linear double-stranded DNA molecule (100 to 225 kbp) protected by an icosahedral capsid made up of 162 hollow-centered capsomeres, a tegument surrounding the nucleocapsid, and a viral envelope derived from host membranes. Upon infection, the linear viral DNA is delivered to the nucleus, where it circularizes to form the viral episome. Depending on several factors, the viral cycle can proceed either to a productive infection or to a state of latency. In either case, the viral genetic information is maintained as extrachromosomal circular DNA. Interestingly, however, certain oncogenic herpesviruses such as Marek''s disease virus and Epstein-Barr virus can be found integrated at low frequencies in the host''s chromosomes. These findings have mostly been viewed as anecdotal and considered exceptions rather than properties of herpesviruses. In recent years, the consistent and rather frequent detection (in approximately 1% of the human population) of human herpesvirus 6 (HHV-6) viral DNA integrated into human chromosomes has spurred renewed interest in our understanding of how these viruses infect, replicate, and propagate themselves. In this review, we provide a historical perspective on chromosomal integration by herpesviruses and present the current state of knowledge on integration by HHV-6 with the possible clinical implications associated with viral integration.Integration of viral genomes into the host''s chromosomes is mandatory for the successful completion of the life cycles of several viruses, including retroviruses and adeno-associated viruses (AAV). In contrast, herpesviruses maintain their genomes as extrachromosomal circular episomes in the nuclei of infected cells without the need for integration. However, there have been several reports of chromosomally integrated herpesvirus (CIHHV) DNA over the years, suggesting that herpesviruses can indeed integrate into the host''s chromosomes under certain conditions. In addition, for a virus such as human herpesvirus 6 (HHV-6), found integrated into the germ lines of approximately 1% of the world''s population, integration may represent more than a sporadic or anecdotal event.Considering that replication of nonintegrated herpesvirus DNA occurs through the well-accepted rolling-circle mechanism, yielding long DNA concatemers that are subsequently cleaved into single-genome equivalents during nucleic acid encapsidation, how replication of linear CIHHV DNA can occur (if it does) remains unknown. In this document, we review cases and reports of integrated nonhuman and human herpesviruses and discuss the outcomes of such events on the life cycles of the viruses and the potential medical consequences of integration.Chromosomal insertions of alphaherpesvirus DNA segments, including those from herpes simplex viruses and equine herpesvirus types 1 and 3, have been reported on numerous occasions in the past (10, 11, 71, 77, 81, 87, 106). In most instances, these events were detected following infection with defective interfering particles or UV-irradiated viral preparations or transfection of sheared or subgenomic viral DNA fragments. The integrated viral genome therefore consists mostly of subgenomic fragments, and there is no possibility for the production of infectious viral particles to occur. Many of the cells carrying integrated viral DNA displayed a transformed phenotype, fueling hypotheses on the oncogenic nature of these viruses. Although the integration of foreign (viral) DNA into chromosomes can cause several anomalies, the intent of this review is to focus on viruses for which integration of full-length viral DNA is documented and to raise, at least theoretically, the possibility that viral replication can occur following integration. Viruses that meet these criteria include Marek''s disease virus (MDV), Epstein-Barr virus (EBV), and HHV-6.     

Modulation of Apoptosis by Herpesviruses

The herpesvirus family of viruses is large, containing over 100 different members, of which 8 infect humans. In this short review, we examine the induction and inhibition of apoptosis by herpesviruses, focusing primarily on the human viruses.     

Herpesviruses: a study of parts

Dormancy, an adaptation to survival in a hostile environment, is a trait common to herpesviruses. Two other features are a large (0.1-0.25 Mb) and mutile (inherently easily mutable) genome. The complete nucleotide sequences of four herpesviruses have recently been determined. This database is unparalleled in allowing the comparative evolutionary study of a complex group of viruses in eukaryotes. In this article, we examine aspects of herpesvirus diversity in the light of recent studies which have revealed characteristics that unify the family at the genetic level.     

Abduction of Chemokine Elements by Herpesviruses

Chemokines play a key role in orchestrating leukocytic recruitment during inflammatory responses, including those to viral infections. Chemokines are soluble cytokines which mediate their effects through specific G protein-coupled, seven-transmembrane receptors which are expressed on a wide range of cells, including monocytes, T-cells, dendritic cells, and NK cells. Analyses of herpesvirus genomes have revealed that these viral pathogens encode their own versions of both chemokines and chemokine receptors. Viral genes encoding chemokine elements were likely to have been acquired from the host genome and have been remodeled during virus evolution to presumably optimize function or acquire new properties not displayed by their cellular homologues. Virus-encoded chemokines and chemokine receptors are important players in the continuing confrontation between viruses and their mammalian hosts. Detailed characterization of these elements will provide a better understanding of how the immune system responds to viral infection and may suggest new antiviral drug targets and new avenues for the development of antiviral therapies. We will review here the chemokine elements encoded by herpesviruses and how they may aid viral infection and propagation.     

Herpesviruses and the Type III Interferon System

Type III interferons (IFNs) represent the most recently discovered group of IFNs. Together with type I IFNs (e.g. IFN-α/β), type III IFNs (IFN-λ) are produced as part of the innate immune response to virus infection, and elicit an anti-viral state by inducing expression of interferon stimulated genes (ISGs). It was initially thought that type I IFNs and type III IFNs perform largely redundant functions. However, it has become evident that type III IFNs particularly play a major role in antiviral protection of mucosal epithelial barriers, thereby serving an important role in the first-line defense against virus infection and invasion at contact areas with the outside world, versus the generally more broad, potent and systemic antiviral effects of type I IFNs. Herpesviruseses are large DNA viruses, which enter their host via mucosal surfaces and establish lifelong, latent infections. Despite the importance of mucosal epithelial cells in the pathogenesis of herpesviruses, our current knowledge on the interaction of herpesviruses with type III IFN is limited and largely restricted to studies on the alphaherpesvirus herpes simplex virus (HSV). This review summarizes the current understanding about the role of IFN-λ in the immune response against herpesvirus infections.     

Herpesviruses in metastatic Lucké renal adenocarcinoma

The etiologic agent of the renal adenocarcinoma of leopard frogs, Rana pipiens, is the Lucké tumor herpesvirus (LTHV). The virus is easily detected with thin section electron microscopy in primary tumors of frogs which have been exposed to a cold environment. Several spontaneous metastatic nodules and a large primary tumor were detected at autopsy of a frog which had been maintained at 4 degrees C for 73 days. LTHV was found not only in the primary tumor, as previously reported, but also was present in metastatic tumor cells in the liver, fat body, and bladder. The presence of LTHV in metastatic cells demonstrates that the differentiated state of primary Lucké tumor cells is retained in its metastatic colonies even at the fine structure level revealed by electron microscopy.     

不同营养评价方法对住院患者营养状况评价的比较及意义

目的:分析比较身高标准体重法、体质指数法(BMI法)、体质指数校正法与生物电阻抗测量方法在住院患者营养评价中的意义。方法:随机抽取我院内科176名患者作为观察对象,用以上4种方法分别进行营养状况评价,测量结果采用单因素卡方分析法和Ridit分析比较。结果:用4种方法评价同一群体住院病人的营养状况时,其结果的差异有显著意义。结论:评判体脂和肥胖时应该首选能反映身体脂肪量及比例和身体内脂肪分布的腰臀比指标。标准体重法、BMI法和BMI校正法三种方法,在评价住院患者的营养状况时,最好能将腰臀比指标与其他指标共同使用。     

福建大头蛙4个地理居群的形态量度比较

比较了福建大头蛙(Limnonectes fujianensis)福建、湖南、浙江和江西4个地理居群的外部形态差异。在测量12个可量性状的基础上,运用统计分析软件SPSS12.0对其中11个性状进行数理统计。主成分分析结果显示,福建居群、浙江居群分别与其他3个居群在外部形态上存在一定差异;聚类分析结果也表明,湖南居群和江西居群聚为一类,福建居群和浙江居群聚为一类,二者之间存在明显差异。     

Herpesviruses remodel host membranes for virus egress

Herpesviruses replicate their DNA and package this DNA into capsids in the nucleus. These capsids then face substantial obstacles to their release from cells. Unlike other DNA viruses, herpesviruses do not depend on disruption of nuclear and cytoplasmic membranes for their release. Enveloped particles are formed by budding through inner nuclear membranes, and then these perinuclear enveloped particles fuse with outer nuclear membranes. Unenveloped capsids in the cytoplasm are decorated with tegument proteins and then undergo secondary envelopment by budding into trans-Golgi network membranes, producing infectious particles that are released. In this Review, we describe the remodelling of host membranes that facilitates herpesvirus egress.     

四种旱生藓类植物的比较结构学观察

对新疆产的４种藓类植物茎、叶的表面及内部结构进行了观察,结果表明：尖叶大帽藓（Ｅｎｃａｌｙｐｔａ ｒｈａｂｄｏｃｕｒｐａ Ｓｃｈｗａｅｇｒ．）茎的中部结构类似于种子植物（单子叶）根的内皮层,其茎表皮也有类似于种子植物表皮毛（腺毛）的腺体。在阔叶紫萼藓（Ｇｒｉｍｍｉａ ｌａｅｖｉｇａｔａ（Ｂｒｉｄ．）Ｂｒｉｄ．）茎的中轴部,厚角组织发达,数层皮部厚壁组织也很发达。小石藓（Ｗｅｉｓｉａ ｃｏｎｔｒｏｖ     

Herpesviruses in Metastatic Lucké Renal Adenocarcinoma

The etiologic agent of the renal adenocarcinoma of leopard frogs, Rana pipiens , is the Lucké tumor herpesvirus (LTHV). The virus is easily detected with thin section electron microscopy in primary tumors of frogs which have been exposed to a cold environment. Several spontaneous metastatic nodules and a large primary tumor were detected at autopsy of a frog which had been maintained at 4°C for 73 days. LTHV was found not only in the primary tumor, as previously reported, but also was present in metastatic tumor cells in the liver, fat body, and bladder. The presence of LTHV in metastatic cells demonstrates that the differentiated state of primary Lucké tumor cells is retained in its metastatic colonies even at the fine structure level revealed by electron microscopy.     

Sorting and Transport of Alpha Herpesviruses in Axons

The alpha herpesviruses, a subfamily of the herpesviruses, are neurotropic pathogens found associated with most mammalian species. The prototypic member of this subfamily is herpes simplex virus type 1, the causative agent of recurrent cold sores in humans. The mild nature of this disease is a testament to the complex and highly regulated life cycle of the alpha herpesviruses. The cellular mechanisms used by these viruses to disseminate infection in the nervous system are beginning to be understood. Here, we overview the life cycle of alpha herpesviruses with an emphasis on assembly and transport of viral particles in neurons.     

Concentration of Oncogenic Herpesviruses by Methyl Alcohol Precipitation

Oncogenic herpesviruses, like many other viruses, can be concentrated effectively from large volumes of culture fluids by precipitation with methanol with good recovery of infectivity.     

Herpesviruses Exploit Several Host Compartments for Envelopment

Enveloped viruses acquire their host‐derived membrane at a variety of intracellular locations. Herpesviruses are complex entities that undergo several budding and fusion events during an infection. All members of this large family are believed to share a similar life cycle. However, they seemingly differ in terms of acquisition of their mature envelope. Herpes simplex virus is often believed to bud into an existing intracellular compartment, while the related cytomegalovirus may acquire its final envelope from a novel virus‐induced assembly compartment. This review focuses on recent advances in the characterization of cellular compartment(s) potentially contributing to herpes virion final envelopment. It also examines the common points between seemingly distinct envelopment pathways and highlights the dynamic nature of intracellular compartments in the context of herpesvirus infections.