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latent and herpesvirus

Ahmed El-Sharkawy, Lobna Al Zaidan, Ahmed Malki
The Epstein-Barr virus (EBV) is the first herpesvirus identified to be associated with human cancers known to infect the majority of the world population. EBV-associated malignancies are associated with a latent form of infection, and several of the EBV-encoded latent proteins are known to mediate cellular transformation. These include six nuclear antigens and three latent membrane proteins (LMPs). In lymphoid and epithelial tumors, viral latent gene expressions have distinct pattern. In both primary and metastatic tumors, the constant expression of latent membrane protein 2A (LMP2A) at the RNA level suggests that this protein is the key player in the EBV-associated tumorigenesis...
2018: Frontiers in Oncology
Stephanie J Wilson, Alex Woody, Avelina C Padin, Jue Lin, William B Malarkey, Janice K Kiecolt-Glaser
Background: Lonely people's heightened risks for chronic health conditions and early mortality may emerge in part through cellular aging. Lonelier people have more severe sympathetic responses to acute stress, increasing their risk for herpesvirus reactivation, a possible path to shorter telomeres. Parasympathetic function may modulate this risk. Purpose: The current study aimed to examine the associations among loneliness, herpesvirus reactivation, and telomere length, with parasympathetic activity as a moderator, in healthy middle-aged and older adults...
August 13, 2018: Annals of Behavioral Medicine: a Publication of the Society of Behavioral Medicine
Claudette L Poole, Scott H James
PURPOSE: The objective of this review was to summarize the recent literature describing the current burden of disease due to herpesviruses in the antiviral and transplant era; describe mechanisms of action of antiviral agents and the development of resistance; summarize the literature of recent antiviral agents brought to market as well as agents under development; and to present literature on future strategies for herpesvirus therapeutics. METHODS: An extensive search of the medical literature related to antiherpesviral therapy was conducted to compose this narrative review...
August 10, 2018: Clinical Therapeutics
Michael A Rak, Jason Buehler, Sebastian Zeltzer, Justin Reitsma, Belen Molina, Scott Terhune, Felicia Goodrum
Human cytomegalovirus, HCMV, is a beta-herpesvirus that establishes a life-long latent infection in its host that is marked by recurrent episodes of reactivation. The molecular mechanisms by which the virus and host regulate entry into and exit from latency remain poorly understood. We have previously reported that UL135 is critical for reactivation, functioning in part by overcoming suppressive effects of the latency determinant UL138 We have demonstrated a role for UL135 in diminishing cell surface levels and inhibiting the return of epidermal growth factor receptor (EGFR) to the cell surface...
August 8, 2018: Journal of Virology
Yan Zhang, Wen Zhang, Wen Liu, Hong Liu, Yong Zhang, Bing Luo
Epstein-Barr virus (EBV) is a ubiquitous oncogenic herpesvirus associated with various human tumors. Latent membrane protein (LMP) 1 is considered a key oncoprotein in some EBV-associated tumors, while it is absent in EBV-associated gastric carcinoma (EBVaGC). In the present study, we did not detect the mRNA or the protein expression of LMP1 in 10 EBVaGC tissue samples, but we found that miRNA-BART16 was more abundantly expressed in EBVaGC primary tissues than in cell lines. It has been reported that EBV-encoded miRNA-BART16 can target the 3'-untranslated regions of LMP1 and negatively regulate its expression...
August 2, 2018: Virus Research
Imane Boumart, Thomas Figueroa, Ginette Dambrine, Benoit Muylkens, Srdan Pejakovic, Denis Rasschaert, Catherine Dupuy
Herpesviruses have a lifecycle consisting of successive lytic, latent and reactivation phases. Only three infected cell proteins (ICPs) have been described for the oncogenic Marek's disease virus (or Gallid herpes virus 2, GaHV-2): ICP4, ICP22 and ICP27. We focus here on ICP22, confirming its cytoplasmic location and showing that ICP22 is expressed during productive phases of the lifecycle, via a bicistronic transcript encompassing the US10 gene. We also identified the unique promoter controlling ICP22 expression, and its core promoter, containing functional responsive elements including E-box, ETS-1 and GATA elements involved in ICP22 transactivation...
August 1, 2018: Journal of General Virology
Anirban Sanyal, Nina Wallaschek, Mandy Glass, Louis Flamand, Darren J Wight, Benedikt B Kaufer
Human herpesvirus 6A (HHV-6A) replicates in peripheral blood mononuclear cells (PBMCs) and various T-cell lines in vitro. Intriguingly, the virus can also establish latency in these cells, but it remains unknown what influences the decision between lytic replication and the latency of the virus. Incoming virus genomes are confronted with the nuclear domain 10 (ND10) complex as part of an intrinsic antiviral response. Most herpesviruses can efficiently subvert ND10, but its role in HHV-6A infection remains poorly understood...
July 29, 2018: Viruses
Asuka Nanbo, Harutaka Katano, Michiyo Kataoka, Shiho Hoshina, Tsuyoshi Sekizuka, Makoto Kuroda, Yusuke Ohba
Infection of Epstein⁻Barr virus (EBV), a ubiquitous human gamma herpesvirus, is associated with various malignancies in B lymphocytes and epithelial cells. EBV encodes 49 microRNAs in two separated regions, termed the BART and BHRF1 loci. Although accumulating evidence demonstrates that EBV infection regulates the profile of microRNAs in the cells, little is known about the microRNAs in exosomes released from infected cells. Here, we characterized the expression profile of intracellular and exosomal microRNAs in EBV-negative, and two related EBV-infected Burkitt lymphoma cell lines having type I and type III latency by next-generation sequencing...
July 19, 2018: Cancers
Zunlin Yang, Tomoyuki Honda, Keiji Ueda
Kaposi's sarcoma (KS)-associated herpesvirus (KSHV) vFLIP, a latent gene of KSHV, was first identified as a FLICE-inhibitory protein (FLIP) protecting cells from apoptosis. The vFLIP protein has been shown to activate the NF-κB signaling involved in spindle morphology formation both in HUVECs infected with KSHV and Kaposi's sarcoma (KS) itself. In this study, we independently established stably vFLIP-expressing cells and showed that they exhibited upregulated NF-κB family protein expression independent of the ability of IKKs to bind vFLIP...
September 2018: Virology
Sang-Hoon Sin, Anthony B Eason, Rachele Bigi, Yongbaek Kim, SunAh Kang, Kelly Tan, Tischan A Seltzer, Raman Venkataramanan, Hyowon An, Dirk P Dittmer
Kaposi Sarcoma-associated herpesvirus (KSHV) KSHV induces B cell hyperplasia and neoplasia such as multicentric Castleman's disease (MCD) and primary effusion lymphoma (PEL). To explore KSHV-induced B cell reprogramming in vivo , we expressed the KSHV latency locus, inclusive of all viral miRNAs, in B cells of transgenic mice in the absence of the inhibitory FcγRIIB receptor. The BALB/c strain was chosen as this is the preferred model to study B cell differentiation. The mice developed hyperglobulinemia, plasmacytosis, and B lymphoid hyperplasia...
July 18, 2018: Journal of Virology
Brian E Crucian, Alexander Choukèr, Richard J Simpson, Satish Mehta, Gailen Marshall, Scott M Smith, Sara R Zwart, Martina Heer, Sergey Ponomarev, Alexandra Whitmire, Jean P Frippiat, Grace L Douglas, Hernan Lorenzi, Judith-Irina Buchheim, George Makedonas, Geoffrey S Ginsburg, C Mark Ott, Duane L Pierson, Stephanie S Krieger, Natalie Baecker, Clarence Sams
Recent studies have established that dysregulation of the human immune system and the reactivation of latent herpesviruses persists for the duration of a 6-month orbital spaceflight. It appears certain aspects of adaptive immunity are dysregulated during flight, yet some aspects of innate immunity are heightened. Interaction between adaptive and innate immunity also seems to be altered. Some crews experience persistent hypersensitivity reactions during flight. This phenomenon may, in synergy with extended duration and galactic radiation exposure, increase specific crew clinical risks during deep space exploration missions...
2018: Frontiers in Immunology
Derek J Hanson, Joshua A Hill, David M Koelle
Human herpesvirus (HHV) 6 is thought to remain clinically latent in most individuals after primary infection and to reactivate to cause disease in persons with severe immunosuppression. In allogeneic hematopoietic stem cell transplant recipients, reactivation of HHV-6 species B is a considerable cause of morbidity and mortality. HHV-6B reactivation is the most frequent cause of infectious meningoencephalitis in this setting and has been associated with a variety of other complications such as graft rejection and acute graft versus host disease...
2018: Frontiers in Immunology
William Dunker, Yu Song, Yang Zhao, John Karijolich
Kaposi’s sarcoma-associated herpesvirus (KSHV) is a human gammaherpesvirus and the etiological agent of Kaposi’s sarcoma. KSHV is also causally associated with the development of lymphoproliferative diseases, including primary effusion lymphoma (PEL). KSHV reactivation from latency plays an integral role in the progression to KSHV-associated disease as several lytic proteins have angiogenic and anti-apoptotic functions essential to the tumor microenvironment. Thus, restriction of KSHV reactivation represents an attractive therapeutic target...
July 6, 2018: Viruses
Teresa Frisan, Noemi Nagy, Dimitrios Chioureas, Marie Terol, Francesca Grasso, Maria G Masucci
We have addressed the role of bacterial co-infection in viral oncogenesis using as model Epstein-Barr virus (EBV), a human herpesvirus that causes lymphoid malignancies and epithelial cancers. Infection of EBV carrying epithelial cells with the common oral pathogenic Gram-negative bacterium Aggregatibacter actinomycetemcomitans (Aa) triggered reactivation of the productive virus cycle. Using isogenic Aa strains that differ in the production of the cytolethal distending toxin (CDT) and purified catalytically active or inactive toxin, we found that the CDT acts via induction of DNA double strand breaks and activation of the Ataxia Telangectasia Mutated (ATM) kinase...
July 6, 2018: International Journal of Cancer. Journal International du Cancer
Orkide O Koyuncu, Margaret A MacGibeny, Lynn W Enquist
Alpha herpesviruses are common pathogens of mammals. They establish a productive infection in many cell types, but a life-long latent infection occurs in PNS neurons. A vast majority of the human population has latent HSV-1 infections. Currently, there is no cure to clear latent infections. Even though HSV-1 is among the best studied viral pathogens, regulation of latency and reactivation is not well understood due to several challenges including a lack of animal models that precisely recapitulate latency/reactivation episodes; a difficulty in modeling in vitro latency; and a limited understanding of neuronal biology...
May 2018: Future Virology
Maria K Smatti, Duaa W Al-Sadeq, Nadima H Ali, Gianfranco Pintus, Haissam Abou-Saleh, Gheyath K Nasrallah
The Epstein-Barr virus (EBV) is a DNA lymphotropic herpesvirus and the causative agent of infectious mononucleosis. EBV is highly prevalent since it affects more than 90% of individuals worldwide and has been linked to several malignancies including PTLDs, which are one of the most common malignancies following transplantation. Among all the EBV genes, most of the recent investigations focused on studying the LMP-1 oncogene because of its high degree of polymorphism and association with tumorigenic activity...
2018: Frontiers in Oncology
Hosni A M Hussein, Ikenna B Okafor, Lia R Walker, Usama M Abdel-Raouf, Shaw M Akula
Oncogenic viruses carry an extensive arsenal of oncogenes for hijacking cellular pathways. Notably, variations in oncogenes among tumor-producing viruses give rise to different mechanisms for cellular transformation. Specifically, Kaposi's sarcoma-associated herpesvirus (KSHV) is an oncogenic virus able to infect and transform a variety of cell types. The oncogenicity of KSHV disseminates from the virus' ability to induce and encode a wide variety of both cellular and viral oncogenes. Such an array of cellular and viral oncogenes enables KSHV to induce the malignant phenotype of a KSHV-associated cancer...
June 23, 2018: Archives of Virology
Richard B Tunnicliffe, Richard F Collins, Hilda D Ruiz Nivia, Rozanne M Sandri-Goldin, Alexander P Golovanov
The UL69 protein from human cytomegalovirus (HCMV) is a multifunctional regulatory protein and a member of the ICP27 protein family conserved throughout herpesviruses. UL69 plays many roles during productive infection, including the regulation of viral gene expression, nuclear export of intronless viral RNAs, and control of host cell cycle progression. Throughout the ICP27 protein family, an ability to self-associate is correlated with the functions of these proteins in transactivating certain viral genes. Here, we determined the domain boundaries of a globular ICP27 homology domain of UL69, which mediates self-association, and characterized the oligomeric state of the isolated domain...
June 19, 2018: MBio
Kaelin M Bernier, Lynda A Morrison
Herpes simplex virus (HSV)-1 and HSV-2 cause painful blisters and shallow ulcers in exposed skin and mucosae during primary or recurrent infection. In addition, recurrent and potentially blinding HSV-1 infections of the eye afflict nearly half a million persons in the U.S. Current clinical therapies rely on nucleoside analog drugs such as acyclovir (ACV) or ganciclovir to ameliorate primary infections and reduce the frequency and duration of reactivations. However, these treatments do not fully suppress viral shedding and drug-resistant mutants develop in the eye and in vulnerable, immunosuppressed patients...
August 2018: Antiviral Research
Alexander L Greninger, Pavitra Roychoudhury, Hong Xie, Amanda Casto, Anne Cent, Gregory Pepper, David M Koelle, Meei-Li Huang, Anna Wald, Christine Johnston, Keith R Jerome
Herpes simplex viruses (HSVs) are difficult to sequence due to their large DNA genome, high GC content, and the presence of repeats. To date, most HSV genomes have been recovered from culture isolates, raising concern that these genomes may not accurately represent circulating clinical strains. We report the development and validation of a DNA oligonucleotide hybridization panel to recover nearly complete HSV genomes at abundances up to 50,000-fold lower than previously reported. Using copy number information on herpesvirus and host DNA background via quantitative PCR, we developed a protocol for pooling for cost-effective recovery of more than 50 HSV-1 or HSV-2 genomes per MiSeq run...
June 27, 2018: MSphere
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