Herpesviridae

Herpesviridae

Viruses are considered non-living because they lack many of the characteristics scientists associate with being alive. This description of the eukaryotic DNA virome is relatively unbiased in that it did not rely on virus culture or virus-specific assays to define the normal viral flora. Previous studies have analyzed the DNA damage response (DDR) induced upon AAV replication to understand how it controls AAV replication. Integration into host telomeres also aids in reactivation from the quiescent state of infection. In this study we investigate DNA of HCV driven HCC for the possibility of integration of all known viral genomes. Mailing address: Centre for Virology, Division of Infection and Immunity, Royal Free and University College Medical School (UCL campus), Windeyer Institute of Medical Sciences, 46 Cleveland St., London W1T 4JF, United Kingdom. In one of these cell lines, a third species of MDV DNA could be detected with properties reminiscent of covalently closed circular DNA.

Herpesviridae
Mutants in the KKRK motif that are enhanced in DNA binding are nonetheless impaired in activating direct targets, such as polyadenylated nuclear RNA, and indirect targets, such as ORF50 itself. Despite current control through the use of vaccines, viral evolution leads to increasing virulence and vaccine breaks on a cyclical basis [6, 7]. Such levels are typical of viral chromosomal integration (4) and are strikingly different from the situation in immunocompetent persons with latent but not integrated HHV-6, in whom viral DNA is detected at the much lower level of around 1 copy per 104 to 105 leukocytes (3), i.e., 2 log10 copies/ml. The molecular mechanisms controlling lytic replication and latent persistence of herpesviruses have been the subject of intense study in recent years, aided largely by advances made in the field of viral genetics. Our goal is to understand how the lamina and its associated proteins regulate the epigenetics of genes through the study of HSV infection of human cells. 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. Xu, K.

HHV-6 chromosomal integration was first discovered in the mid 1990’s, when Luppi and colleagues identified the presence of integrated HHV-6 DNA into the chromosomes of freshly isolated peripheral blood mononuclear cells (PBMC) (5–7). We and others demonstrated that forced expression of Rta, encoded by KSHV open reading frame 50 (ORF50), induces the full cycle of productive lytic reactivation in PEL cells (15, 27, 30, 39). Since Delecluse and Hammerschmidt (1993) first reported on the potential for MDV to exist in an integrated state, it has been a subject of debate as to whether the virus integrates stably (and where) into the chicken genome or is merely associated and how such associations might be germane to pathogenesis and oncogenesis. Since that early report, complete genome sequences have been reported for several MDV strains and BAC vectors containing the full-length MDV genome have been cloned [15–20]. Figure 1 HMGB1 transcription and expression during HSV-2 infection. Only one case of CIHHV-6 and concurring encephalomyelitis, subsequently relieved by antivirals, has so far been reported in an immunocompetent subject (12). We investigated the details of integration on both intra-and inter-chromosomal levels by mapping the location of MDV integrations.

If the answer is “no,” the risk is low that exposure to your gene transfer technology will be followed by gene therapy-related delayed adverse events. KSHV was found in Kaposi’s sarcoma tissues with representational difference analysis (RDA) as the eighth human herpesvirus by Chang et al.

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Herpesviridae

Herpesviridae

The unfolded protein response (UPR), induced by the accumulation of improperly folded proteins within the ER lumen (ER stress), is associated with multiple cellular responses such as neurodegeneration and apoptosis. Several other common pathogens have been less consistently associated with atherosclerosis. One serotype is known, but the virulence between strains is variable. This phenomenon was associated with IE1-mediated inactivation of the p53 and Rb tumor suppressor proteins, and activation of the PI3-K/AKT signaling pathway [41]. Aujeszky’s disease can cause death of 80-90% of nonimmune animals or provoke other bacterial or viral diseases. The most common sites of involvement were the buccal/labial mucosa (27%), tongue (25%), and gingiva (18%). The virus can also infect the genital tract and cause pustular vulvovaginitis and balanoposthitis.

Herpesviridae
Since TSP-1 inhibits angiogenesis and GFAP is associated with a more differentiated astrocytic phenotype [45], these results suggested that, in addition to promoting glioma cell mitogenesis, expression of IE1 in glioma cells may also promote GBM angiogenesis, and a de-differentiated state, along with loss of tumor suppressor activity. Interestingly, we found that expression of HCMV IE1 in normal human astrocytes or normal fibroblasts resulted in either no change in proliferation or a decreased proliferation, respectively. 1985. In the last few years, other groups have made further advances with respect to elucidating how HCMV gene products may impact gliomagenesis. 2. Human cytomegalovirus (HCMV), with 250 kbp in its genome, is among the largest of the herpesviruses. Hepatitis H may more or less be the name given to the next hepatitis virus to be isolated.

Since telomerase activation can lead to cellular immortalization and telomerase activation has been observed in 90% of cancers [46], these findings suggest that HCMV IE1 mediated activation of telomerase may contribute to oncogenesis in glioma. Consistent with these observations, Scheurer et al. found that the level of IE1 expression in malignant gliomas was positively correlated to the grade of tumor, with GBM having the highest levels of expression [31]. The papillomaviruses are associated with usually benign (nonthreatening) but widespread tumours, called papillomas or polyps, occurring in human skin and the genital tract. While IE1 expression in a tumor cell may promote important oncogenic signaling pathways, we also became interested in the possibility that HCMV might promote sustained RTK activation, which is a hallmark of GBM pathogenesis. We and others had observed that HCMV attachment caused activation of RTK signaling, and that a RTK was potentially causing HCMV-mediated PI3-K/AKT signaling [48]. In exploring this phenomenon, we discovered that activation of the PDGFRα receptor was essential for HCMV infection [49].

Furthermore, we observed that the HCMV gB envelope glycoprotein binds specifically to PDGFRα upon viral attachment and functions like the authentic ligand PDGF in terms of activating downstream RTK signaling of the PI3-K/AKT signaling pathway [49]. Blockade of PDGFRα with a blocking antibody or with the PDGFRα small molecule inhibitor Gleevec® completely inhibited HCMV entry into the cell, viral expression and replication [49]. These findings immediately raised the possibility that expression of the HCMV gB glycoprotein on the cell surface of glial precursor stem cells or GBM cells that overexpress PDGFRα may facilitate autocrine or paracrine activation of the PDGFRα signaling pathway, which plays a major role in glioma pathogenesis. Ongoing studies in our laboratory are investigating this hypothesis. In addition to sustained mitogenesis and inhibition of tumor suppressor function, another key event in oncogenesis is blockade of cellular differentiation. If HCMV infection of NPCs could promote the PDGFRα – PI3K/AKT signaling pathway while simultaneously blocking their ability to differentiate, this would greatly increase the likelihood of neoplastic transformation. This hypothetical scenario could occur in HCMV infected NPCs, since these cells are fully permissive to HCMV infection [50] and since HCMV gene products block the ability of NPCs to differentiate into neurons and astrocytes [51–53].

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Herpesviridae

Herpesviridae

Abstract: DESCRIPTION (provided by applicant): Vical Inc. However, the effects of the TK gene in infectious laryngotracheitis virus (ILTV) have not been clearly elucidated. No virus reactivation was obtained in calves, which received vaccines A or E. None of 14 control horses shed virus or became viraemic or seroconverted prior to challenge. To give you an idea of how common they are, chickenpox is caused by a herpesvirus (Varicella-Zoster virus). So are cold sores (HSV-1) and mono (Epstein-Barr virus). Herpesviridae is an old and diverse family of viruses.

They infect an astonishing variety of animal taxa, including mammals and mollusks, suggesting that the family could be hundred of millions of years old: long before humans were humans. Vaccinated mice were infected with MHV-68-OVA but showed reduced viral loads in the acute and latent phase of challenge infection. Numerous researchers of the 19th century applied the ways of science to the study of these mysterious infectious agents. Thus, gG-deficient ILTV appears to have potential for use in large-scale poultry vaccination programmes when administered via eye-drop or in drinking water. German doctor Paul Unna determined a way to clinically differentiate herpes lesions from syphyllis lesions in 1896. In 1893, French scientist Emile Vidal proved experimentally that herpes lesions were indeed transferable from one person to another. Another important breakthrough in the understanding of herpesviruses came in 1925, when American virologist Ernest Goodpasture showed that herpesviruses travel through neurons.

In 1939, Australian microbiologist suggested that herpesviruses reside primarily in neurons during a period of latency, when no symptoms occur. In 1973, American scientists Jack Stevens and Margery Cook confirmed this theory. Because herpesviruses infect so many people, there is a great impetus for the development of antivirals and vaccines. One of these new drugs is an enzyme nucleotidyltransferase inhibitor. This enzyme is normally used for transferring a phosphorous-containing group from one molecule to another. Nucleotidyltransferase is used in the synthesis of DNA and of tRNA. There are no licensed drugs that target the nucleotidyltransferase of HSV-1 or HSV-2, so this new drug could work in conjunction with existing ones.
Herpesviridae

Another experimental therapy actually uses a herpesvirus as a diagnostic agent. A recent study from the University of Birmingham used host-derived, genetically modified cytotoxic T cells that selectively destroyed cancer cells infected with Epstein-Barr virus. Since Epstein-Barr virus is frequently implicated in the oncogenesis of nasopharylgeal carcinoma (representing 18% of cancers in Southeast Asia). The specific protein that the genetically engineered cytotoxic T cells target is viral protein LMP2, which blocks tyrosine kinase signaling so that the B-lymphocytes in which the virus goes latent don’t undergo apoptosis. Human herpesviruses are among the most complex known viruses that infect humans. Their capsids are spherical or pleiomorphic, and they have envelopes. These structural features make herpesviruses look like “fried eggs” when viewed with a scanning electron microscope.

While large for a virus, they are still quite small at 150-200 nm in diameter. They have linear double stranded DNA genomes like we do. At 120-230 KB in length, their genomes are quite large for a virus. Herpesviruses genomes include between 70 and 200 genes. Herpesviruses replicate in 2 phases. A hallmark feature of herpesviruses is their ability to go latent. Oftentimes, the virus infects a different type of cell than it does when it is actively replicating.

For the virus to reproduce, it first has to enter the host cell, which it does by attaching its host gB, gC, gD, and gH proteins to the host cell receptors. The virus fuses with the host cell membrane, and loses its envelope. The capsid is transported to the nucleus, where its genome is replicated. Herpesviruses express the genes of their genome in a series of steps, which are known as kinetic classes. The kinetic classes describe the manner in which certain herpesvirus genes are transcribed and translated at different times relative to each other. The early genes are accessory proteins involved in regulatory functions, while the later ones are proteins form the capsid and support the envelope: the structural proteins. At the time of writing, we don’t have the ability to completely clear a herpesvirus infection from the body.

However, there are several drugs that help reduce viral load and symptoms. Is used to treat chickenpox, shingles (Varicella Zoster virus), genital herpes (HSV-2), herpes of the skin, lips, and mouth (HSV-1 or HSV-2), and neonatal herpes (typically HSV-2). It doesn’t cure herpes, but it can reduce the viral load and alleviate symptoms. Acyclovir can also be used to treat Epstein-Barr virus and cytomegalovirus infections, but it isn’t as effective as it is against HSV-1, HSV-2, and VZV. Acyclovir is typically administered intravenously or as an oral capsule/tablet, or as an oral liquid. It is a guanosine analogue, which means that the drug is similar in chemical composition to a guanine base (found in DNA and RNA), but it inhibits the viral DNA polymerase, the main enzyme used to replicate DNA. Acyclovir is a well-established antiviral medication that the WHO endorses for treating herpesvirus infections.

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Herpesviridae

Herpesviridae

Abstract Objective. Decoration options let you color tree leaves by metadata. For amino acid sequences, ViPR uses the MUSCLE (Multiple Sequence Comparison by Log-Expectation) algorithm. We found that RCMV influenced vascular remodeling by increased apoptosis of SM-α-actin positive cells in the media layer, decreased extracellular matrix deposits and increased intimal hyperplasia. In addition, these viruses have co-evolved with, and shaped, the immune systems of their hosts. h. Or, should the doses of immunosuppressive agents be increased to suppress inflammatory activity?
Herpesviridae

Latency 0, sometimes referred to as ‘in vivo latency, is the type of latency observed in non-dividing circulating memory B cells of healthy carriers; it is possible that the majority of these cells express no viral genes at all, but that a minority may express non-coding RNAs. ἕρπειν (herpein) für „kriechen“ ab, was auf die kriechende Ausbreitung der Hautläsionen bei einer Infektion mit dem Herpes-simplex-Virus hindeutet, dem bekanntesten Vertreter der Familie. Die Virionen der Herpesviridae sind zwischen 120 und 200 nm im Durchmesser groß; sie gehören damit neben der Familie Poxviridae zu den größten Viren. In elektronenmikroskopischen Abbildungen (TEM) zeigt sich meist eine unregelmäßige, eingedellte Virushülle, was auf die Zerstörung der empfindlichen Hülle während der Präparation zurückzuführen ist. Zwischen Hülle und Kapsid befindet sich ein im Vergleich zu anderen Viren großer Raum (Matrixraum), der mit zahlreichen Strukturproteinen angefüllt ist. 1984. Die Größe des Matrixraumes erhöht den Kontrast zwischen Hülle und Kapsid in der TEM-Darstellung, was die typische sogenannte „Spiegeleiform“ der Herpesviridae hervorruft.

Moreover, NPC patients are the only EBV carriers that reproducibly develop LMP2 specific antibody responses[41, 42], indicating a significant level of LMP2 protein expression.

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Herpesviridae

Herpesviridae

Herpesviridae
A 73-year-old woman with a history of deceased donor kidney transplantation and a recent cytomegalovirus (CMV) infection, presented to the emergency department with an altered mental status. Most dangerous form of skin cancer Originates in melanocytes in the epidermis Multiplies to form larger tumor on skin surface if given enough time Then, melanoma can grow down the skin and reaches blood and lymphatic vessels Cytomegalovirus Herpes Simplex Virus & EBV Melanoma Herpesviridae and Cancer How are viruses used to treat cancer? Please see the identifier information above for retrieving further details from the government database. Gene Therapy Viral Gene Therapy Current Research T-VEC Trial Therapy How does the T-VEC vaccine work? For stabilization of therapeutic effect, the prevention of synchronization and palindromias carrying out preventive actions in a subtherapeutic dose for the following scheme is reasonable: – at an easy and medium-weight current — 1-2 months till 8-10 of drops pass 2 times; – at a heavy current-2-4 months till 8-10 drops – 2 times a day. there is no right or wrong answer. References Introduction to: Note: all three viruses, have similar characteristics!

(Nordqvist, 2009) (Okruzhnov, 2000) (Mefferet, 2015) Intense UV exposure Weakened immune system Family history Frequent sunburns Fair skin Having excessive and unusual moles Melanoma is usually not fatal if identified and treated early, if not the cancer can advance to other parts of the body and become incurable. f Viruses that influence and cause cancers are called oncoviruses Encourage and prolong tumor development Human tumor cell life is extended and made virutally indestructable Stimulates continuous and endless growth of cancer cells unless killed They are found hidden inside bacteria and tumor cells, or other viruses (Clark, 2007) A process of inserting genes into tumor cells to treat gene related cancers First clinical trial in 1990 A total of 1970+ trials have been made since then A form of therapy that substitutes surgery and medication In 2006, 2 patients with metastatic melanoma showed successful results in trial (Liu, Xia & Zhong, 2014) A type of gene therapy that uses viral vectors that deliver gene into tumor cells Genetically engineered gene is introduced into tumor Non-harmful to healthy cells Selectively destructs cancerous cells by mass replication Tumor cells lyse and replicated viruses infect other tumor cells (Liu et al., 2014) Essentially, viral gene therapy eliminates oncoviruses through oncolytic methods: selective replication in cancerous cells and amplifies have toxic effects to cancer cells Modified version of the HSV has selective viral properties – attacking tumors and stimulating immune response actions 436 patients worldwide are participants of a phase 3 clinical trial These patients had severe, inoperable melanoma Each received T-VEC injection or a “control” immunotherapy Talimogene laherparepvec (Mundell, 2015) Fewer side effects than most immunotherapy Strongest response from less advanced melanoma patients (and no prior tx exposure) Survival rate for stage 3/4 melanoma with tx: 41 months Survival rate for control group: 22 months Is being considered first-line treatment for early stage melanoma (Mundell, 2015) Delivering the gene into the correct cell, tissue Disrupt functioning of other genes Most likely contraindicated in a lot of conditions Invasive Cost (Genetic Science Learning Center, 2014) Introdution to Herpesviridae Cytomegalovirus, Herpes Simplex Virus, Epstein Barr Virus What is melanoma? Signs, symptoms, risk factors Treatment: Gene therapy Viruses and Treatment T-VEC Study Pros and Cons Source: www.biovex.com/oncovex.html By: Jinju & Tsering Clark, H. It is encased in a glycoprotein-bearing lipid bilayer envelope. The prevention of all cancers. Chula Vista, CA: New Century Press.

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Herpesviridae

Herpesviridae

==Introduction== [[Image:Herpes_simplex_virions,_TEM.jpg|thumb|300px|right|Transmission electron micrograph of herpes simplex virus. Most dangerous form of skin cancer Originates in melanocytes in the epidermis Multiplies to form larger tumor on skin surface if given enough time Then, melanoma can grow down the skin and reaches blood and lymphatic vessels Cytomegalovirus Herpes Simplex Virus & EBV Melanoma Herpesviridae and Cancer How are viruses used to treat cancer? Outline The Herpesviridae Family Cytomegalovirus Epstein Barr Virus Herpes Simplex Virus Environmental / Risk Factors Viruses and Tumors/Cancers Unusual looking skin growth or moles on the skin as shown below: Treatment: Gene Therapy How can viruses treat melanoma? A few case reports and studies report an association between CMV and VZV infection. Due to limitations on the use of archived patient specimens and/or tissue quality, not all specimens could be evaluated for all antibodies and in situ hybridization. The antibodies used are specific for HCMV immediate early (“IE”), early and late (“E/L”), or late antigens (“L”) (Figures 1 and 2 ). As controls, we used monoclonal antibodies specific for smooth muscle actin (SMA) (data not shown) and CD34 (Figure 1, l ).

These antibodies react to smooth muscle cells and vascular endothelial cells, respectively, but not breast epithelial cells, and serve as IgG 2α and IgG 1 isotype positive and negative monoclonal antibody controls, respectively. As additional negative controls, we performed immunostaining in the absence of primary antibody for all cases (data not shown). Figure 1 Immunohistochemical detection of HCMV in normal breast and breast cancer. (a, b) Examples of HCMV IE immuonreactivity in isolated area of normal ductal epithelium in normal breast from a reduction mammoplasty patient are presented. Low (a, 40×) and higher (b, 100×) power views of the same area of immunoreactive epithelium demonstrate discrete perinuclear and cytoplasmic epithelial cell staining. No IE immunoreactivity is detected in two different specimens obtained from normal reduction mammoplasty (c and d, 40×; e is 100× magnification of d). The precise arrangement of the DNA within the core is not known.
Herpesviridae

Early and late (E/L) immunoreactivity is demonstrated in the tumor epithelial cells, but not the stroma, from an area of ductal carcinoma in situ (DCIS) in a patient with infiltrative ductal carcinoma (g, 40×, h, 100×). Positive control immunostaining for IE immunoreactivity is shown in HCMV infected pneumocytes from an AIDS patient with CMV pneumonia (i, 100×). 6. 6,239,257 B1 and it too has been found to be cytotoxic to cancer cells. J. The outcome of HCMV infection is frequently determined by the status incompetency of host immunity and, in the case of intra uterine fetal HCMV infection, the developmental stage at the time of infection. Varicella zoster virus is responsible for chickenpox shingles and zooster.

The human cytomegalovirus (HCMV) can cause a wide variety of different diseases as outlined in detail further below. cytomegalovirus. The HCMV-E/L immunoreactivity was detected in a similar cellular pattern as that of IE antigen, with a staining pattern restricted to epithelium (Figure 1, g-h ; Figure 2, b ). Monoclonal antibody immunoreactivity with HCMV-L was detected in 56% of breast cancer specimens and 39% of normal controls (p = 0.227; Table 1 ). The pattern of late antigen cellular localization was also similar to IE and E/L immunoreactivity (Figure 1, j, k ; Figure 2, c ). HCMV late antigen was detected, in general, at a less intense level, although occasional rare cells were very intensely positive for late antigen (Figure 2, c ). In some of the tumors there were areas of homogenous low level immunoreactivity to IE, E/L and L antigens, while in other tumors there were scattered foci of positive tumor cells.

The intensity of immunostaining varied significantly from tumor cell to tumor cell within any given tumor (e.g., Figure 1, j, k ; Figure 2 ).

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