virus activation

..Elucidating the molecular mechanism of virus activation, we could show that catecholamines directly stimulate the HCMV immediate-early (IE) enhancer/promoter in ..

....

..Our findings have broad implications for physiological triggers of latent viral infections, such as herpesviral reactivation and persistence in the host...

....

..We are currently investigating other signals, such as the endoplasmic reticulum stress response proteins, which act upstream of XBP-1s, to identify other interacting factors that initiate and/or amplify the lytic switch...

..By showing that HIV-1 infection directly reactivates latent KSHV, our results suggest a direct role of HIV-1 in the onset of KS in coinfected individuals...

..These data demonstrate that HCMV can activate KSHV lytic replication and suggest that HCMV could influence KSHV pathogenesis...

....

..Our data suggest that the induction of most of the KSHV lytic cycle genes requires additional protein expression after the expression of Rta...

..Therefore, manipulation of the stability and function of IRF7 by the KSHV RTA transcription factor provides an unexpected regulatory strategy for circumventing the innate immune defence system...

..Thus there is a crucial link between the differentiation of myeloid cells and transcriptional reactivation of latent virus which is likely to play a key role in viral pathogenesis...

..Cytomegalovirus is the most common viral opportunistic infection in immunocompromised patients. However, recent studies have demonstrated active cytomegalovirus infection in nonimmunosuppressed intensive care unit patients...

....

....

..Reactivation of CMV from latency results in serious morbidity and mortality in immunocompromised transplant recipients. The mechanism by which CMV reactivates from latency has not been well understood...

..Together, these findings suggest that MAPK pathways might have general roles in regulating the life cycle of KSHV by mediating both viral infection and switch from viral latency to lytic replication...

..The persistence and enrichment of HIV receptor-positive inflammatory cells in the genitalia help explain the inability of anti-HSV-2 therapy to reduce HIV acquisition...

....

..The precise role of cytomegalovirus (CMV) infection in contributing to outcomes in critically ill immunocompetent patients has not been fully defined...

....

....

....

..These results suggest that potent, selective HDAC inhibitors may allow improved targeting of persistent proviral HIV infection, and define parameters for in vivo studies using SAHA...

..Mitomycin C-stimulated N15 induction required RecA-dependent autocleavage of LexA and expression of AntC protein. Thus, a cellular repressor whose activity is regulated by DNA damage controls N15 prophage induction...

..In addition, such cell lines may be of value in evaluating targeted therapies to gammaherpesvirus-related tumors...

..05). The number of URS increased along with the EBV-DNA expression and decrease of SIgA levels. These results suggest that the appearance of URS is associated with reactivation of EBV and reduction of SIgA during training...

..EBV reactivation should be confirmed by measuring salivary EBV DNA or infectious virus...

..It was found that the UL112-113 locus was able to activate the complete KSHV lytic cycle, while the UL122-123 locus, encoding the IE1 and IE2 proteins, known to be strong transactivators, did not...

..Thus, phages may participate in a far more expansive network of genetic information exchange among bacteria of different species than originally thought, with important implications for the evolution of human pathogens...

..Thus, the various drugs now available for treatment of HCMV disease (e.g. ganciclovir, acyclovir and foscarnet), may also prove to be useful in the treatment of other, more widespread diseases...

..1 expression was not detected in TPA-induced BAC36Delta50-containing cells. These results showed that K-Rta is essential for lytic viral reactivation and transactivation of viral genes contributing to DNA replication...

..Here we discuss the Rta/Orf50 of KSHV in comparison to the Rta/Orf50s of other gammaherpesviruses in an effort to identify structural motifs, mechanisms of action, and modulating host factors...

..This links B-cell terminal differentiation to KSHV lytic reactivation...

....

..UL kinases of alpha- and betaherpesviruses also induce the disassembly of the nuclear lamina through similar sites on lamin A/C, suggesting a conserved mechanism for the nuclear egress of herpesviruses...

..Rather, the most consistent models of action involve LAT expression playing a cis-acting role in a very early stage of the reactivation process...

..In the latter subset, LG appear to provide a nonlethal block of viral reactivation...

..These results demonstrate the potential of a memory immune response against gammaherpesviruses to alter long-term latency and suggest that limiting long-term latent infection in a clinically relevant situation is an attainable goal...

..These data suggest that human studies using antiviral agents during critical illness are warranted...

....

..Whether this variability in the CD8(+) T-cell response within individuals is associated with the frequency of viral reactivation warrants further study...

..These findings may have important implications in the development of CMV-specific adoptive immunotherapy strategies...

..Because TSA overcomes the block, viral gene silencing may involve histone deacetylase-based modification of viral chromatin, which might account for the covalently closed circular conformation of quiescent HCMV genomes...

..Finally, the prophylactic use of lamivudine in inactive HBV carriers with haemato-oncological malignancy prevents interruptions in their treatment for primary disease as a result of HBV reactivation...

..These last results strongly suggest that there is a posttranscriptional constraint on the expression of ICP0 protein during reactivation from latency and that this constraint is mediated by LAT...

....

..This provides a new model for analysis of the interrelationships among herpesvirus latency, the immune system, and chronic disease of the great vessels...

..Such information may be useful in determining which patients would benefit most from prophylactic antiviral therapy during cytotoxic chemotherapy...

..Taken together, these findings are consistent with a model in which chronic virus infection of CD40(-/-) mice is maintained through virus reactivation in the lungs and reseeding of latency reservoirs...

..The presence of Th2-type cytokines (IL-4 and IL-6) indicates a role for antibody. Thus, several clearance mechanisms may be at work...

..However, the induction mechanism of HMB is still unclear...

..219 at the epithelial surface. These findings demonstrate that KSHV lytic activation occurs as keratinocytes differentiate into a mature epithelium, and it may be responsible for the presence of infectious KSHV in saliva...

..A more detailed understanding of the basic mechanisms underlying the establishment and long-term maintenance of HIV-1 reservoirs will be critical in developing new eradication approaches...

..In contrast, 2 of 5 control patients had HBV reactivation. Lamivudine prophylaxis in HBsAg carriers receiving immunosuppressive therapy may prevent HBV reactivation and hepatic failure...

..As gamma-herpesviruses primarily cause human disease during chronic infection, these chronic disease genes may be important targets for therapeutic intervention...

..A high HBV DNA level (>10(5) copies/mL) was the most important risk factor for HBV reactivation, and its lowering by administration of nucleoside analogues before transplantation should be considered...

....

..Taken together, these analyses will aide future studies for identifying M2 interacting partners and B-cell signaling pathways that are manipulated by the M2 protein...

..B cells themselves may also play a subtle role in modulating pathogenesis by influencing tropism...

..Collectively, these findings demonstrate that ICP0 is required to induce efficient reactivation of HSV-1 from neuronal latency...

..We propose that one molecular mechanism of Mta-mediated transactivation is a direct effect on transcription by direct and indirect promoter association...

....

..To investigate the effect of acetylsalicylic acid on ocular shedding of herpes simplex virus type 1 (HSV-1)...

..To our knowledge, this is the first report to show that a microbial protein can drive a latently infected B cell into EBV replication...

..The ability to provoke slow reactivation of quiescent genomes, in conjunction with cell survival, represents a novel property for a viral structural protein...

..Both of the small LAT-specific RNAs have the potential to base pair with the ICP4 mRNA. These two small LAT RNAs may play a role in the latency-reactivation cycle by reducing apoptosis and/or by reducing ICP4 RNA expression...

..The process of switching from latency to replication is not well understood, particularly in response to DNA stress; hence, the focus of this study is on an EBV-positive NPC model...

..The timing of virus recovery from all sites suggests that MCMV observed in the injected eye is from in situ reactivation of virus and not from spread of virus from extraocular sites via infected PBLs...

..Latency-like infection in nonneural cell types may potentially reactivate, leading to multifocal necrosis, fibrosis, and dystrophic calcifications, as observed in advanced congenital varicella syndrome...

..We conclude that while ICP0 is important and perhaps essential for infectious virus production during reactivation in vivo, this protein is not required and appears to play no major role in the initiation of reactivation in vivo...

..The presence of HIV-1 preintegration reservoir was assessed in an in vitro experimental model of latent HIV-1 infection, and in patients treated or not with highly active antiretroviral therapy (HAART)...

..Taken together, our data suggest that open chromatin at EBV BZLF1 and BRLF1 promoters is not sufficient to activate EBV lytic cycle gene expression...

..These findings suggest a new model with a number of challenges towards our understanding, molecular targeting and therapeutic intervention in NPC...

..Even so, TK(+) virus could still confer the pathogenic phenotype to a TK(-) mutant, somehow providing sufficient TK activity in trans to permit a TK(-) mutant to reactivate from latently infected ganglia...

..Production of RA during the lytic form of EBV infection may enhance viral replication by promoting keratinocyte differentiation...

..The aim of this study was to investigate the short-term effect of infliximab on reactivation of several harmful latent viruses...

..This new model contributes fresh insight into the natural history of EBV infection and the pathogenesis of EBV-associated epithelial disease...

....

..Regardless, the results presented in this study strongly support the hypothesis that LAT's antiapoptosis activity is the dominant function that enhances HSV-1's spontaneous reactivation phenotype...

..Neonatal HSV-1 infection therefore appears to be mainly caused by hematogenous vertical transmission, and the viruses that colonize the offspring CNS are capable of molecular reactivation after a period of latency...

..The efficacy of this virus in cultured human glioma cell lines, its safety, confirmed by its inability to reactivate, and its attenuated neurovirulence make DM33 a promising oncolytic agent for tumor therapy...

..Viral genes expressed during the establishment phase may serve as targets for therapies to interrupt this process...

..These potent 6-aminoquinolones were further evaluated for their broad-spectrum antiviral properties...

....

..We suggest that incorporation of the LR gene mutation into existing modified live vaccines would prevent reactivation from latency in neural and nonneural sites and would thus prevent transmission to other animals...

..The ELISPOT approach to targeting the HIV-1-Ag-SCs could be a useful method for identifying latently HIV-1-infected CD4(+) T cells carrying replication-competent HIV-1 in patients responding to HAART...

..Given that the expression of these genes may be important for tumor development, MTX could play a role in the future management of KSHV-associated malignancies...

....

....

..Utilizing a viral CXCR2 homologue to enhance replication and reactivation from latency represents a novel mechanism by which gammaherpesviruses can subvert the immune response...

..To review our previous studies regarding herpes simplex virus type 1 (HSV-1) corneal latency in the rabbit lamellar keratoplasty (LK) and penetrating keratoplasty (PKP) models...

..The relevance to the virus life-cycle in neurones in vivo is discussed...

..5 gene appeared to be at least partially responsible for the reduced neurovirulence of KOS compared with McKrae. However, there appeared to be no 'defect' in the KOS ICP34.5 function required for efficient spontaneous reactivation...

..We will discuss immunological implications of ie1 gene expression during latency and will speculate a bit on how CD8 T cells might trigger latency-associated ie1 gene expression in a regulatory circuit...

..Late expression of the LMP1 protein may account for this...

....

..Furthermore, although the ORF 50 proteins of HVS strains A11 and C488 are structurally divergent, they were both capable of inducing the lytic replication cycle in this model of HVS latency...

..The results raise a question as to the role of LMP2A in inhibition of disruption of virus latency in vivo, where LMP2A expression has been expected to be low as in Akata cells...

..the control of HIV transcription by the dominant-negative form of C/EBPbeta protein and inhibit resurgent virus activation in the lung and the development of associated lesions...

..A detailed understanding of the activation of this pathway may provide new opportunities for treatment of EBV-associated cancers and also of similar cancers considered EBV-negative, that develop in the immunosuppressed. ..

..tea used by healers in Samoa and now in preclinical development for eradicating HIV/AIDS virus through latent virus activation, and at evaluation of the promising anticancer activity of the analogs, their role in PKC signaling, and ..

..In general, these studies will explore the immunobiology of murine allograft acceptance and its relationship to allograft tolerance. ..

..In general, these studies will explore the immunobiology of murine allograft acceptance, and its relationship to allograft tolerance. ..

..Studies will also determine whether LAT encoded proteins inhibit apoptosis, and whether these proteins are necessary for the latency reactivation cycle. ..

..These studies will improve our understanding of the interaction between respiratory viruses and late pulmonary complications after HCT, which will ultimately enable us to formulate more rational treatment strategies. ..

..abstract_text> ..

..abstract_text> ..

..Training in ethics of conduct of research is also provided, as is access to seminars, collaborators and classes in related fields. ..

..These studies will yield information on the molecular basis of viral latency and reactivation which in turn provides the foundation for future studies designed to eradicate neurologic disease in the elderly produced by VZV...

..abstract_text> ..

..An ex vivo model of HSV-1 reactivation in explanted mouse trigeminal ganglia is proposed as an efficient means for determining effective strategies for the delay or inhibition of reactivation. ..

..abstract_text> ..

..These studies will yield information on the molecular basis of viral latency and reactivation which in turn provides the foundation for future studies designed to eradicate neurologic disease in the elderly produced by VZV...

..Novel and specific viral mutants will be constructed based on the results of HSV-DNA binding and transient expression assays. ..

....

..It is anticipated that in achieving this goal, significant insight will be accomplished in the identification of pathways involved in blocking HSV-1 reactivation and spread within the nervous system. ..

....

..Aim 3. What regulates the cell-type specificity of HTLV transformation? What is the role of IL15 in Tax transgenic animals? ..

..This could be particularly important during an influenza pandemic and may be more broadly applicable to other respiratory viruses. ..

..g., vaccine or gene transfer) to reduce the incidence of infection or reduce the capacity of latent virus to reactivate. ..

....

..This application seeks to demonstrate that a vaccine directed against cmvlL-10 should be included as one of the components. ..

....

..The data are likely to lead to a new understanding of how CD8 T cells function in the control of persistent viral infections and mechanisms of CD8 T cell activation. ..

..abstract_text> ..

....

..These studies utilize 2 unique model systems to define the leukemogenic pathway mediated by HTLV-1. ..

..We will investigate the effect of NK activation in secondary lymphoid organs on DC maturation and alloreactive as well as EBV specific T cell polarization. ..

..These studies will allow us to understand better how tumors can be detected by the immune system and how we can enhance immune responses to cancer. ..

....

..These studies should provide information that is important for designing antiviral strategies for HSV and for engineering HSV-2 strains for genital herpes vaccines. ..

..I anticipate that this translational research could lead directly to clinical trials evaluating antigen specific active (vaccines) or passive (adoptive transfer) immunotherapy for AML. ..

..abstract_text> ..

..2c. Characterize the roles of the gammaHV68 M1 protein and v-cyclin in reactivation. 2d. Identify other gammaHV68 genes involved in reactivation. ..