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latent and herpesvirus

Aki Hoji, Susie Xu, Holly Bilben, David T Rowe
The latent state is a critical component of all herpesvirus infections, and its regulation remains one of the most active areas of Epstein-Barr Virus (EBV) research. In particular, identifying environmental factors that trigger EBV reactivation into a virus-productive state has become a central goal in EBV latency research. Recently, a category of chemicals known as inducers of the endoplasmic reticulum unfolded protein response (UPR) have been shown to trigger EBV lytic reactivation in various established EBV-associated lymphoma cell lines...
November 2018: Heliyon
Darren J Wight, Nina Wallaschek, Anirban Sanyal, Sandra K Weller, Louis Flamand, Benedikt B Kaufer
Human herpesvirus-6A and -6B (HHV-6A and -6B) are two closely related betaherpesviruses that infect humans. Upon primary infection they establish a life-long infection termed latency, where the virus genome is integrated into the telomeres of latently infected cells. Intriguingly, HHV-6A/B can integrate into germ cells, leading to individuals with inherited chromosomally-integrated HHV-6 (iciHHV-6), who have the HHV-6 genome in every cell. It is known that telomeric repeats flanking the virus genome are essential for integration; however, the protein factors mediating integration remain enigmatic...
November 21, 2018: Viruses
Richard B Tunnicliffe, Colin Levy, Hilda D Ruiz Nivia, Rozanne M Sandri-Goldin, Alexander P Golovanov
Kaposi's sarcoma-associated herpesvirus (KSHV) transcribes a long noncoding polyadenylated nuclear (PAN) RNA, which promotes the latent to lytic transition by repressing host genes involved in antiviral responses as well as viral proteins that support the latent state. KSHV also expresses several early proteins including ORF57 (Mta), a member of the conserved multifunctional ICP27 protein family, which is essential for productive replication. ORF57/Mta interacts with PAN RNA via a region termed the Mta responsive element (MRE), stabilizing the transcript and supporting nuclear accumulation...
November 20, 2018: Nucleic Acids Research
Takanobu Tagawa, Shaojian Gao, Vishal N Koparde, Mileidy Gonzalez, John L Spouge, Anna P Serquiña, Kathryn Lurain, Ramya Ramaswami, Thomas S Uldrick, Robert Yarchoan, Joseph M Ziegelbauer
Noncoding RNAs have substantial effects in host-virus interactions. Circular RNAs (circRNAs) are novel single-stranded noncoding RNAs which can decoy other RNAs or RNA-binding proteins to inhibit their functions. The role of circRNAs is largely unknown in the context of Kaposi's sarcoma herpesvirus (KSHV). We hypothesized that circRNAs influence viral infection by inhibiting host and/or viral factors. Transcriptome analysis of KSHV-infected primary endothelial cells and a B cell line identified human circRNAs that are differentially regulated upon infection...
November 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
Pavel Dyachenko, Anatoly Dyachenko, Olga Smiianova, Victoria A Kurhanskay, Ruslan Efremin
OBJECTIVE: Introduction: Herpesviruses (HVs) are ubiquitous pathogens that infect humans usually during childhood, followed by a life-long persistence in a latent state in many sites of a body including the nerve cells. After reactivation HVs can affect the Central Nervous System (CNS) becoming a major cause of morbidity and mortality worldwide as well as long-term neurological sequelae. Despite being an important public health problem very few population-based studies were conducted so far in the world and none in Ukraine...
2018: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
Peter A Seeber, Anisha Dayaram, Florian Sicks, Nikolaus Osterrieder, Mathias Franz, Alex D Greenwood
Equid Herpesviruses (EHV) are pathogens of equid and non-equid hosts that can cause disease and fatalities in captivity and in the wild. EHVs establish latent infections but can reactivate, and most EHVs are shed via the nasal passage. Therefore, nasal swabs are generally used for EHV monitoring. However, invasive sampling of wild equids is difficult. While feces is a commonly used substrate for detecting other pathogens, to our knowledge EHVs have never been detected in feces of naturally infected equids. We systematically tested zebra feces for EHV presence by A) establishing nested PCR conditions for fecal DNA extracts, B) controlling for environmental EHV contamination, and C) large-scale testing on a free-ranging zebra population...
November 16, 2018: Applied and Environmental Microbiology
Joshua A Hill, Minako Ikoma, Danielle M Zerr, Ryan S Basom, Vikas Peddu, Meei-Li Huang, Ruth Hall Sedlak, Keith R Jerome, Michael Boeckh, Serge Barcy
Human herpesvirus 6B (HHV-6B) DNA is frequently detected in human samples. Diagnostic assays distinguishing HHV-6B reactivation from latency are limited. This has impaired strategies to diagnose and treat HHV-6B-associated diseases. We used RNA sequencing to characterize and compare the HHV-6B transcriptome in multiple sample types, including 1) whole blood from hematopoietic cell transplant (HCT) recipients with and without HHV-6B plasma viremia; 2) tumor tissue samples from subjects with large B cell lymphoma infected with HHV-6B; 3) lymphoblastoid cell lines (LCLs) from subjects with inherited chromosomally integrated HHV-6B or latent infection with HHV-6B; and 4) HHV-6B Z29 infected SupT1 CD4+ T cells...
November 14, 2018: Journal of Virology
Kendra A Bussey, Sripriya Murthy, Elisa Reimer, Baca Chan, Bastian Hatesuer, Klaus Schughart, Britt Glaunsinger, Heiko Adler, Melanie M Brinkmann
Murine gammaherpesvirus 68 (MHV68) is an amenable small animal model for study of the human pathogens Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus. Here, we have characterized the roles of the endosomal TLR escort protein UNC93B, endosomal TLR7, 9, and 13, and cell surface TLR2 in MHV68 detection. We found that the interferon α (IFNα) response of plasmacytoid dendritic cells (pDC) to MHV68 was reduced in Tlr9-/- cells compared to wildtype (WT), but not completely lost. Tlr7-/- pDC responded similarly to WT...
November 14, 2018: Journal of Virology
Masatoshi Nukui, Christine M O'Connor, Eain A Murphy
Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus for which there is no vaccine or cure. This viral infection, once acquired, is life-long, residing latently in hematopoietic cells. However, latently infected individuals with weakened immune systems often undergo HCMV reactivation, which can cause serious complications in immunosuppressed and immunocompromised patients. Current anti-viral therapies target late stages of viral replication, and are often met with therapeutic resistance, necessitating the development of novel therapeutics...
November 7, 2018: Viruses
Ruoyun Gao, Tingting Li, Brandon Tan, Suzane Ramos da Silva, Jae U Jung, Pinghui Feng, Shou-Jiang Gao
Kaposi's sarcoma-associated herpesvirus (KSHV) has latent and lytic replication phases, both of which contribute to the development of KSHV-induced malignancies. Among numerous factors identified to regulate KSHV life cycle, oxidative stress, caused by imbalanced clearing and production of reactive oxygen species (ROS), has been shown to robustly disrupt KSHV latency and induce viral lytic replication. In this study, we identify an important role of antioxidant defense factor forkhead box protein O1 (FoxO1) in KSHV lifecycle...
November 7, 2018: Journal of Virology
Junqing Guo, Qingmei Li, Clinton Jones
Following acute infection of mucosal surfaces by bovine herpesvirus 1 (BoHV-1), sensory neurons are a primary site for lifelong latency. Stress, as mimicked by the synthetic corticosteroid dexamethasone, consistently induces reactivation from latency. Two viral regulatory proteins (VP16 and bICP0) are expressed within 1 h after calves latently infected with BoHV-1 are treated with dexamethasone. Since the immediate early transcription unit 1 (IEtu1) promoter regulates both BoHV-1 infected cell protein 0 (bICP0) and bICP4 expressions, we hypothesized that the bICP4 protein is also expressed during early stages of reactivation from latency...
November 6, 2018: Journal of Neurovirology
Mara Cirone
Autophagy is a catabolic process strongly involved in the immune response, and its dysregulation contributes to the onset of several diseases including cancer. The human oncogenic gammaherpesviruses, Epstein-Barr virus (EBV) and Kaposi's sarcoma-associated herpesvirus (KSHV), manipulate autophagy, either during the de novo infection or during the lytic reactivation, in naturally latently-infected lymphoma cells. In particular, the gammaherpesvirus infection reduces autophagy in immune cells, such as monocytes, resulting in the impairment of cell survival and cell differentiation into dendritic cells (DCs), which are essential for initiating and regulating the immune response...
October 31, 2018: Viruses
Ming Lo, Jia Zhu, Scott G Hansen, Timothy Carroll, Christina Farr Zuend, Laura Nöel-Romas, Zhong-Min Ma, Linda Fritts, Meei-Li Huang, Sijie Sun, Ying Huang, David Koelle, Louis J Picker, Adam Burgener, Lawrence Corey, Christopher J Miller
Herpes simplex virus-2 (HSV-2) is a common sexually transmitted infection with a highly variable clinical course. Many infections quickly become subclinical, with episodes of spontaneous virus reactivation. To study the host/HSV-2 interactions an animal model of subclinical HSV-2 infection is needed. In an effort to develop a relevant model, rhesus macaques (RM) were inoculated intravaginally with two or three HSV-2 strains (186, 333 and/or G); total dose 1x107 pfu HSV-2 per animal. Infectious HSV-2 and HSV-2 DNA was consistently shed in vaginal swabs for the first 7-14 days after each inoculation...
October 17, 2018: Journal of Virology
Hanna Carolina Campos Ferreira, Mateus Gandra Campos, Pedro Marcus Pereira Vidigal, Marcus Rebouças Santos, Otávio Valério DE Carvalho, Gustavo Costa Bressan, Juliana Lopes Rangel Fietto, Eduardo Paulino DA Costa, Márcia Rogéria Almeida, Abelardo Silva Júnior
Bovine herpesvirus 1 and 5 (BoHV-1 and -5) are antigenically and genetically related and can establish latent infection. We aimed to analyze the applicability of the milk sample to detect latently BoHV-infected cattle. BoHV-1 non-vaccinated clinically healthy cows from five dairy cattle herds (herd 1, n=24; herd 2, n=39; herd 3, n=39; herd 4, n=36; herd 5, n=70) were studied. We confirmed the presence of BoHV-1, and for the first time, BoHV-5 in the milk of naturally infected dairy cattle.
October 2, 2018: Journal of Veterinary Medical Science
Shaohui Wang, Alexander V Ljubimov, Ling Jin, Klaus Pfeffer, Mitchell Kronenberg, Homayon Ghiasi
Recently, we reported that the herpesvirus entry mediator (HVEM; TNFRSF14: CD270) is upregulated by the latency-associated transcript (LAT) of HSV-1 and that the absence of HVEM affects latency-reactivation but not primary infection in ocularly infected mice. gD has been shown to bind to HVEM. LIGHT (TNFSF14), CD160 and BTLA (B- and T-lymphocyte attenuator) also interact with HVEM and can interfere with HSV gD binding. It was not known if LIGHT, CD160 or BTLA affected the level of latency-reactivation in the trigeminal ganglia (TG) of latently infected mice...
October 3, 2018: Journal of Virology
Oliver Manners, James C Murphy, Alex Coleman, David J Hughes, Adrian Whitehouse
Kaposi's Sarcoma-associated herpesvirus (KSHV) and Epstein Barr virus (EBV) are the causative agents of several malignancies. Like all herpesviruses, KSHV and EBV undergo distinct latent and lytic replication programmes. The transition between these states allows the establishment of a lifelong persistent infection, dissemination to sites of disease and the spread to new hosts. Latency-associated viral proteins have been well characterised in transformation and tumourigenesis pathways; however, a number of studies have shown that abrogation of KSHV and EBV lytic gene expression impairs the oncogenesis of several cancers...
September 27, 2018: Current Opinion in Virology
Victoria A Jefferson, Kaley A Barber, Fouad S El-Mayet, Clinton Jones, Bindu Nanduri, Florencia Meyer
Bovine herpesvirus 1 (BoHV-1) is one of several microbes that contributes to the development of the bovine respiratory disease (BRD) and can also induce abortions in cattle. As other alpha- herpesvirinae subfamily members, BoHV-1 efficiently replicates in many cell types and subsequently establishes a life-long latent infection in sensory neurons. BoHV-1 encodes more than 70 proteins that are expressed in a well-defined manner during productive infection. However, in silico open reading frame (ORF) prediction of the BoHV-1 genome suggests that the virus may encode more than one hundred proteins...
September 14, 2018: Viruses
Sharon E Hopcraft, Samantha G Pattenden, Lindsey I James, Stephen Frye, Dirk P Dittmer, Blossom Damania
Kaposi's sarcoma-associated herpesvirus (KSHV) is the etiologic agent of three human malignancies, the endothelial cell cancer Kaposi's sarcoma, and two B cell cancers, Primary Effusion Lymphoma and multicentric Castleman's disease. KSHV has latent and lytic phases of the viral life cycle, and while both contribute to viral pathogenesis, lytic proteins contribute to KSHV-mediated oncogenesis. Reactivation from latency is driven by the KSHV lytic gene transactivator RTA, and RTA transcription is controlled by epigenetic modifications...
September 2018: PLoS Pathogens
Bhupesh K Prusty, Nitish Gulve, Suvagata Roy Chowdhury, Michael Schuster, Sebastian Strempel, Vincent Descamps, Thomas Rudel
Human herpesvirus 6A and 6B frequently acquires latency. HHV-6 activation has been associated with various human diseases. Germ line inheritance of chromosomally integrated HHV-6 makes viral DNA-based analysis difficult for determination of early stages of viral activation. We characterized early stages of HHV-6 activation using high throughput transcriptomics studies and applied the results to understand virus activation under clinical conditions. Using a latent HHV-6A cell culture model in U2OS cells, we identified an early stage of viral reactivation, which we define as transactivation that is marked by transcription of several viral small non-coding RNAs (sncRNAs) in the absence of detectable increase in viral replication and proteome...
2018: NPJ Genomic Medicine
Julie A Hicks, Nares Trakooljul, Hsiao-Ching Liu
A shared feature of herpesviruses is their ability to enter a latent state following an initially lytic infection. Marek's disease virus serotype 1 (MDV-1) is an oncogenic avian herpesvirus. Small RNA profiling studies have suggested that microRNAs (miRNAs) are involved in viral latency. Sodium butyrate treatment is known to induce herpesvirus reactivation. The present study was undertaken to determine transcriptome and miRNome changes induced by sodium butyrate in 2 MDV-transformed cell lines, RP2 and CU115...
August 31, 2018: Poultry Science
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