Herpesviridae最新文献

{"title":"Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis.","authors":"Charles S Cobbs","doi":"10.1186/2042-4280-2-10","DOIUrl":"https://doi.org/10.1186/2042-4280-2-10","url":null,"abstract":"<p><p> Human cytomegalovirus (HCMV) was first reported to be strongly associated with human malignant gliomas in 2002. HCMV is a herpesvirus that causes congenital brain infection and multi-organ disease in immumocompromised individuals. Malignant gliomas are the most common and aggressive adult brain tumors and glioblastoma multiforme (GBM), the highest grade glioma, is associated with a life expectancy of less than two years. HCMV gene products encode for multiple proteins that can promote the various signaling pathways critical to tumor growth, including those involved in mitogenesis, mutagenesis, apoptosis, inflammation, angiogenesis, invasion and immuno-evasion. Several groups have now demonstrated that human malignant gliomas are universally infected with HCMV and express gene products that can promote key signaling pathways in glioma pathogenesis. In this review I discuss specific HCMV gene products that we and others have recently found to be expressed in GBM in vivo, including the HCMV IE1, US28, gB and IL-10 proteins. The roles these HCMV gene products play in dysregulating key pathways in glioma biology, including the PDGFR, AKT, STAT3, and monocyte/microglia function are discussed. Finally, I review emerging human clinical trials for GBM based on anti-HCMV strategies.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"10"},"PeriodicalIF":0.0,"publicationDate":"2011-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-10","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30234053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of murine cytomegalovirus IE-3 specific shRNA is dependent on intragenic target site due to multiple transcription initiation sites.","authors":"Brendan Marshall,&nbsp;Ming Zhang,&nbsp;Sally S Atherton","doi":"10.1186/2042-4280-2-9","DOIUrl":"https://doi.org/10.1186/2042-4280-2-9","url":null,"abstract":"<p><strong>Background: </strong>Murine cytomegalovirus (MCMV) is closely related to human cytomegalovirus (HCMV) which is responsible for a variety of diseases, including retinitis, in immunocompromised individuals. Small inhibitory RNA molecules directed against essential viral regulatory genes may prove clinically useful.</p><p><strong>Methods: </strong>Small hairpin RNAs (shRNAs) directed against the essential MCMV immediate early-3 gene (IE-3) were designed and tested in vitro at m.o.i.'s of 2 and 0.2 to determine if virus replication could be inhibited.</p><p><strong>Results: </strong>At m.o.i. = 2, a MCMV IE-3 specific shRNA specific for sequences at the beginning of exon 5 inhibited virus replication with a maximum decrease in virus titer of approximately two logs at day 5 p.i. Surprisingly, however, at m.o.i. = 0.2, the same shRNA enhanced virus replication. In the latter case, the main IE-3 product observed in infected cells was not the expected 88 kd full length IE-3 protein observed at high m.o.i. but rather a truncated 45 kd form of this protein. Rapid analysis of 5' cDNA ends (5' RACE) indicated that substantial differences exist in the transcript profile produced by the IE-3 gene at low and high m.o.i. early after infection and that multiple transcripts are produced under both conditions. One such transcript, which originated in exon 5 of the IE-3 gene, was located outside the region targeted by our shRNA and was the major transcript produced at low m.o.i. Targeting of this exon 5 transcript with a second shRNA resulted in inhibition of virus replication at both low and high m.o.i.</p><p><strong>Conclusions: </strong>These studies indicate that IE-3 has a complex transcriptional profile and that shRNA targeting of this and other viral regulatory genes which produce multiple transcripts may have unexpected effects on virus replication.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"9"},"PeriodicalIF":0.0,"publicationDate":"2011-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30000822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the role of Epstein-Barr virus in the pathogenesis of T and NK cell lymphoproliferations.","authors":"Christopher P Fox,&nbsp;Claire Shannon-Lowe,&nbsp;Martin Rowe","doi":"10.1186/2042-4280-2-8","DOIUrl":"https://doi.org/10.1186/2042-4280-2-8","url":null,"abstract":"<p><p> Epstein-Barr virus (EBV) is a highly successful herpesvirus, colonizing more than 90% of the adult human population worldwide, although it is also associated with various malignant diseases. Primary infection is usually clinically silent, and subsequent establishment of latency in the memory B lymphocyte compartment allows persistence of the virus in the infected host for life. EBV is so markedly B-lymphotropic when exposed to human lymphocytes in vitro that the association of EBV with rare but distinct types of T and NK cell lymphoproliferations was quite unexpected. Whilst relatively rare, these EBV-associated T and NK lymphoproliferations can be therapeutically challenging and prognosis for the majority of patients is dismal. In this review, we summarize the current knowledge on the role of EBV in the pathogenesis of these tumours, and the implications for treatment.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 ","pages":"8"},"PeriodicalIF":0.0,"publicationDate":"2011-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30126690","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of human cytomegalovirus in motile spermatozoa and spermatogenic cells in testis organotypic culture.","authors":"Victor A Naumenko,&nbsp;Yurii A Tyulenev,&nbsp;Sergei A Yakovenko,&nbsp;Lubov' F Kurilo,&nbsp;Ludmila V Shileyko,&nbsp;Aleksander S Segal,&nbsp;Larisa E Zavalishina,&nbsp;Regina R Klimova,&nbsp;Anton S Tsibizov,&nbsp;Sergei V Alkhovskii,&nbsp;Alla A Kushch","doi":"10.1186/2042-4280-2-7","DOIUrl":"https://doi.org/10.1186/2042-4280-2-7","url":null,"abstract":"<p><strong>Background: </strong>The presence of human cytomegalovirus (HCMV) in male genital tract suggests its vertical transmission with spermatozoa and the development of a potentially dangerous fetal infection. The objective of the present study was to evaluate the possibility of intracellular HCMV localization in male germ cells and to examine the effect of the virus on human spermatogenesis.</p><p><strong>Methods: </strong>Semen samples from 91 infertile and 47 fertile men were analyzed. HCMV was detected by real time PCR, rapid culture method and PCR in situ. Human testis organotypic culture and quantitative karyological analysis were used to investigate viral effects on spermatogenesis. Localization of HCMV in immature germ cells and spermatozoa was studied by immunostaining with monoclonal antibodies and ultrastructural analysis of infected organotypic culture.</p><p><strong>Results: </strong>Viral DNA was detected in 12.3% samples of motile spermatozoa, while infectious activity only in 2.9% infertile and fertile men without statistically significant intergroup difference. According to PCR in situ, the mean percentage of infected cell in both groups was 1.5% (0.25%-15%), which can serve as a criterion for evaluating the risk of HCMV transmission. In HCMV-infected organotypic culture viral antigens were identified in spermatides on day 4, in spermatogonia and spermatocytes on day 8, and in spermatozoa on day 14. Empty and full capsides and virions were visualized in germ cells by electron microscopy. The number of cells before introduction in culture was taken for 100%. On day 14 infected culture contained 36.8% spermatogonia, 18.7% spermatocytes, 27.6% round spermatides and 42.5% elongated spermatides; in comparison with 82.2%, 51.5%, 70.4% and 65.7% in uninfected culture, respectively (all p < 0.05). There were no changes in the number and viability of spermatozoa.</p><p><strong>Conclusions: </strong>HCMV was detected in male germ cells, both in sperm samples and in testis organotypic culture. The virus may infect immature germ cells which develop to mature HCMV-carrying spermatozoa. A considerable decrease in the number of immature germ cells indicates that HCMV produces a direct gametotoxic effect and can contribute to male infertility.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2011-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29969576","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytomegalovirus-induced immunopathology and its clinical consequences.","authors":"Stefania Varani,&nbsp;Maria Paola Landini","doi":"10.1186/2042-4280-2-6","DOIUrl":"https://doi.org/10.1186/2042-4280-2-6","url":null,"abstract":"<p><p> Human cytomegalovirus (CMV) is a ubiquitous DNA virus that causes severe disease in patients with immature or impaired immune systems. During active infection, CMV modulates host immunity, and CMV-infected patients often develop signs of immune dysfunction, such as immunosuppression and autoimmune phenomena. Furthermore, active viral infection has been observed in several autoimmune diseases, and case reports have linked primary CMV infection and the onset of autoimmune disorders. In addition, CMV infection promotes allograft rejection and graft-versus-host disease in solid organ and bone marrow transplant recipients, respectively, further implicating CMV in the genesis and maintenance of immunopathological phenomena. The mechanisms by which CMV could induce inhibition of host defense, inflammation, and autoimmunity are discussed, as is the treatment of virus-induced immunopathology with antivirals.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2011-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29799843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating herpes simplex type 1 (HSV-1)-specific CD8+ T cells do not access HSV-1 latently infected trigeminal ganglia.","authors":"Susanne Himmelein,&nbsp;Anthony J St Leger,&nbsp;Jared E Knickelbein,&nbsp;Alexander Rowe,&nbsp;Michael L Freeman,&nbsp;Robert L Hendricks","doi":"10.1186/2042-4280-2-5","DOIUrl":"https://doi.org/10.1186/2042-4280-2-5","url":null,"abstract":"<p><strong>Background: </strong>Therapeutic vaccines can be designed to enhance existing T cell memory populations for increased protection against re-infection. In the case of herpes simplex virus type 1, recurrent disease results from reactivation of latent virus in sensory ganglia, which is controlled in part by a ganglia-resident HSV-specific memory CD8+ T cell population. Thus, an important goal of a therapeutic HSV-1 vaccine would be to enhance this population.</p><p><strong>Methods: </strong>HSV-1-infected mice were treated with TAK-779 to block CCR5- and CXCR3-mediated CD8+ T cell migration during both acute and latent infections. Additionally, HSV-1-specific CD8+ T cells were transferred into HSV-1 latently infected mice to mimic the effect of a therapeutic vaccine, and their migration into trigeminal ganglia (TG) was traced during steady-state latency, or during recovery of the TG-resident memory CD8+ T cell population following stress-, and corticosterone-induced depletion and HSV-1 reactivation from latency. Bromodeoxy uridine (BrdU) incorporation measured cell proliferation in vivo.</p><p><strong>Results: </strong>TAK-779 treatment during acute HSV-1 infection reduced the number of infiltrating CD8+ T cells but did not alter the number of viral genome copies. TAK-779 treatment during HSV latency did not affect the size of the TG-resident memory CD8+ T cell population. Transferred HSV-specific CD8+ T cells failed to access latently infected TG during steady-state latency, or during recovery of the TG resident HSV-specific CD8+ T cell population following exposure of latently infected mice to stress and corticosterone. Recovery of the HSV-specific CD8+ T cell population after stress and corticosterone treatment occurred with homeostatic levels of cell division and did not require CD4+ T cell help.</p><p><strong>Conclusions: </strong>Our findings are consistent with the notion that the CD8+ T cells in latently infected TG are a tissue-resident memory (Trm) population that is maintained without replenishment from the periphery, and that when this population is disrupted, it recovers without proliferation or detectable recruitment of HSV-specific CD8+ T cells from the blood. The compartmentalization of the HSV-specific CD8+ memory T cell population in latently infected TG will complicate the design of therapeutic vaccines.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"5"},"PeriodicalIF":0.0,"publicationDate":"2011-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29761756","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cytolytic T lymphocytes from HLA-B8+ donors frequently recognize the Hodgkin's lymphoma associated latent membrane protein 2 of Epstein Barr virus.","authors":"Ming L Tsang,&nbsp;Christian Münz","doi":"10.1186/2042-4280-2-4","DOIUrl":"https://doi.org/10.1186/2042-4280-2-4","url":null,"abstract":"<p><p> Epstein Barr virus (EBV) is a lymphotrophic γ-herpesvirus that infects more than 90% of the adult human population. It transforms B cells in vitro and is associated with lymphomas in vivo. In most EBV carriers the emergence of these malignancies, however, is prevented by T cell mediated immune control. Part of this control is mediated by CD8+ T cells, which mainly target a subset of viral nuclear antigens, EBNA3A, B and C, in healthy EBV carriers. In HLA-B8 positive individuals, the dominant CTL response is biased towards recognition of EBNA3A. However, spontaneously arising EBV-associated malignancies, such as Hodgkin's lymphoma and nasopharyngeal carcinoma do not express EBNA3s and instead express latent membrane protein 2 (LMP2) as well as LMP1 and EBNA1. Here we describe the new HLA-B8 restricted, LMP2 derived CD8+ T cell epitope, LMP2345-352. Although the frequency of LMP2345-352 specific CD8+ T cells is usually lower than immunodominant EBNA3A specific CD8+ T cells in fresh blood, the former can be expanded in the majority of HLA-B8+ EBV carriers after 1 week co-culture with peptide pulsed dendritic cells. We demonstrate that LMP2345-352 specific CD8+ T cells secrete IFN-γ and kill both peptide pulsed targets as well as HLA-B8 matched LCL and LMP2 expressing Hodgkin's lymphoma cells. We suggest that cytotoxic CD8+ T cell responses against LMP2 coexist with the immunodominant EBNA3 specific responses in healthy EBV carriers and help to resist EBV associated malignancies.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"4"},"PeriodicalIF":0.0,"publicationDate":"2011-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29761761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tegument protein control of latent herpesvirus establishment and animation.","authors":"Rhiannon R Penkert,&nbsp;Robert F Kalejta","doi":"10.1186/2042-4280-2-3","DOIUrl":"https://doi.org/10.1186/2042-4280-2-3","url":null,"abstract":"<p><p> Herpesviruses are successful pathogens that infect most vertebrates as well as at least one invertebrate species. Six of the eight human herpesviruses are widely distributed in the population. Herpesviral infections persist for the life of the infected host due in large part to the ability of these viruses to enter a non-productive, latent state in which viral gene expression is limited and immune detection and clearance is avoided. Periodically, the virus will reactivate and enter the lytic cycle, producing progeny virus that can spread within or to new hosts. Latency has been classically divided into establishment, maintenance, and reactivation phases. Here we focus on demonstrated and postulated molecular mechanisms leading to the establishment of latency for representative members of each human herpesvirus family. Maintenance and reactivation are also briefly discussed. In particular, the roles that tegument proteins may play during latency are highlighted. Finally, we introduce the term animation to describe the initiation of lytic phase gene expression from a latent herpesvirus genome, and discuss why this step should be separated, both molecularly and theoretically, from reactivation.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"3"},"PeriodicalIF":0.0,"publicationDate":"2011-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29761766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy in herpesvirus immune control and immune escape.","authors":"Graham S Taylor,&nbsp;Josef Mautner,&nbsp;Christian Münz","doi":"10.1186/2042-4280-2-2","DOIUrl":"https://doi.org/10.1186/2042-4280-2-2","url":null,"abstract":"<p><p> Autophagy delivers cytoplasmic constituents for lysosomal degradation, and thereby facilitates pathogen degradation and pathogen fragment loading onto MHC molecules for antigen presentation to T cells. Herpesviruses have been used to demonstrate these novel functions of autophagy, which previously has been primarily appreciated for its pro-survival role during starvation. In this review, we summarize recent findings how macroautophagy restricts herpesvirus infections directly, how macroautophagy and chaperone mediated autophagy contribute to herpesviral antigen presentation on MHC molecules, and which mechanisms herpesviruses have developed to interfere with these pathways. These studies suggest that herpesviruses significantly modulate autophagy to escape from its functions in innate and adaptive immunity.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2011-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29761760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immune modulation in EBV infection.","authors":"Shunbin Ning","doi":"10.1186/2042-4280-2-1","DOIUrl":"https://doi.org/10.1186/2042-4280-2-1","url":null,"abstract":"<p><p> Epstein-Barr Virus (EBV) belongs to the gammaherpesvirus family, members of which are oncogenic. Compared with other closely related herpesviruses, EBV has developed much more elaborate and sophisticated strategies for subverting host immune system, which may account for its high prevalence in immune competent hosts. Thus, study of EBV-specific immune dysregulation is important for understanding EBV latency and oncogenesis, and will identify potential molecular targets for immunotherapeutic interventions. Here I summarize the recent findings of individual EBV products in regulating host immune responses, with emphasis on the innate immune modulation.</p>","PeriodicalId":89143,"journal":{"name":"Herpesviridae","volume":"2 1","pages":"1"},"PeriodicalIF":0.0,"publicationDate":"2011-01-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/2042-4280-2-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29761759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}