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latent and herpesvirus

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
Alex Evilevitch
The cell decision between lytic and lysogenic infection is strongly influenced by dynamics of DNA injection into a cell from a phage population, as phages compete for limited resources and progeny. However, what controls the timing of viral DNA ejection events was not understood. This in vitro study reveals that DNA ejection dynamics for phages can be synchronized (occurring within seconds) or desynchronized (displaying minutes-long delays in initiation) based on mobility of encapsidated DNA, which in turn is regulated by environmental factors, such as temperature and extra-cellular ionic conditions...
September 4, 2018: ELife
Mathieu Mancini, Silvia M Vidal
A majority of the world population is infected with herpes simplex viruses (HSV; human herpesvirus types 1 and 2). These viruses, perhaps best known for their manifestation in the genital or oral mucosa, can also cause herpes simplex encephalitis, a severe and often fatal disease of the central nervous system. Antiviral therapies for HSV are only partially effective since the virus can establish latent infections in neurons, and severe pathological sequelae in the brain are common. A better understanding of disease pathogenesis is required to develop new strategies against herpes simplex encephalitis, including the precise viral and host genetic determinants that promote virus invasion into the central nervous system and its associated immunopathology...
August 2018: Mammalian Genome: Official Journal of the International Mammalian Genome Society
Donna Collins-McMillen, Jason Buehler, Megan Peppenelli, Felicia Goodrum
Human cytomegalovirus (HCMV) is a beta herpesvirus that establishes a life-long persistence in the host, like all herpesviruses, by way of a latent infection. During latency, viral genomes are maintained in a quieted state. Virus replication can be reactivated from latency in response to changes in cellular signaling caused by stress or differentiation. The past decade has brought great insights into the molecular basis of HCMV latency. Here, we review the complex persistence of HCMV with consideration of latent reservoirs, viral determinants and their host interactions, and host signaling and the control of cellular and viral gene expression that contributes to the establishment of and reactivation from latency...
August 20, 2018: Viruses
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 2018: Clinical Therapeutics
Michael A Rak, Jason Buehler, Sebastian Zeltzer, Justin Reitsma, Belen Molina, Scott Terhune, Felicia Goodrum
Human cytomegalovirus, HCMV, is a betaherpesvirus that establishes a lifelong 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 targeting epidermal growth factor receptor (EGFR) for turnover...
October 15, 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...
September 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...
September 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
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