| murine gammaherpesvirus-68 expands, but does not activate, cd11b+ gr-1+ splenocytes in vivo. | murine gammaherpesvirus 68 (hv-68) is an efficient pathogen, capable of infecting and establishing lifelong latency in rodents. while many studies have demonstrated the ability of this viral infection to modulate immune responses, a unifying mechanism for hv-68-induced subversion of a protective host response remains elusive. we questioned whether infection with hv-68 could expand a population of myeloid derived suppressor cells (mdsc) as one mechanism for altering protective immunity. | 2012 | 22507226 |
| murine gammaherpesvirus 68 infection protects lupus-prone mice from the development of autoimmunity. | gammaherpesvirus infections, such as those caused by ebv, have been suggested to promote the development of autoimmunity. to test this idea, we infected healthy wt and lupus-prone b6.sle123 mice with an ebv-related and rodent-specific gammaherpesvirus, γhv68. although acute γhv68 infection increased autoantibody levels for 4 to 6 wk, latent infection inhibited these responses for 1 y. the inhibition of autoantibody expression was only observed in b6.sle123 females and not in males, which already ... | 2012 | 22474381 |
| tracking murine gammaherpesvirus 68 infection of germinal center b cells in vivo. | infection of mice with murine gammaherpesvirus 68 (mhv68) provides a tractable small animal model to study various aspects of persistent gammaherpesvirus infection. we have previously utilized a transgenic mhv68 that expresses enhanced yellow fluorescent protein (eyfp) to identify infected cells. while this recombinant mhv68 has been useful for identifying infected cell populations by flow cytometry, it has been suboptimal for identification of infected cells in tissue sections due to the high s ... | 2012 | 22427999 |
| virion endocytosis is a major target for murid herpesvirus-4 neutralization. | herpesviruses consistently transmit from immunocompetent carriers, implying that their neutralization is hard to achieve. murid herpesvirus-4 (muhv-4) exploits host igg fc receptors to bypass blocks to cell binding, and ph-dependent protein conformation changes to unveil its fusion machinery only after endocytosis. nevertheless, neutralization remains possible by targeting the virion glycoprotein h (gh)-gl heterodimer, and the neutralizing antibody responses of muhv-4 carriers are improved by bo ... | 2012 | 22377583 |
| viral cyclins mediate separate phases of infection by integrating functions of distinct mammalian cyclins. | gammaherpesvirus cyclins have expanded biochemical features relative to mammalian cyclins, and promote infection and pathogenesis including acute lung infection, viral persistence, and reactivation from latency. to define the essential features of the viral cyclin, we generated a panel of knock-in viruses expressing various viral or mammalian cyclins from the murine gammaherpesvirus 68 cyclin locus. viral cyclins of both gammaherpesvirus 68 and kaposi's sarcoma-associated herpesvirus supported a ... | 2012 | 22319441 |
| tiled microarray identification of novel viral transcript structures and distinct transcriptional profiles during two modes of productive murine gammaherpesvirus 68 infection. | we applied a custom tiled microarray to examine murine gammaherpesvirus 68 (mhv68) polyadenylated transcript expression in a time course of de novo infection of fibroblast cells and following phorbol ester-mediated reactivation from a latently infected b cell line. during de novo infection, all open reading frames (orfs) were transcribed and clustered into four major temporal groups that were overlapping yet distinct from clusters based on the phorbol ester-stimulated b cell reactivation time co ... | 2012 | 22318145 |
| herpesvirus glycoproteins undergo multiple antigenic changes before membrane fusion. | herpesvirus entry is a complicated process involving multiple virion glycoproteins and culminating in membrane fusion. glycoprotein conformation changes are likely to play key roles. studies of recombinant glycoproteins have revealed some structural features of the virion fusion machinery. however, how the virion glycoproteins change during infection remains unclear. here using conformation-specific monoclonal antibodies we show in situ that each component of the murid herpesvirus-4 (muhv-4) ent ... | 2012 | 22253913 |
| role of endoplasmic reticulum stress in age-related susceptibility to lung fibrosis. | the incidence of idiopathic pulmonary fibrosis (ipf) increases with age. the mechanisms that underlie the age-dependent risk for ipf are unknown. based on studies that suggest an association of ipf and γherpesvirus infection, we infected young (2-3 mo) and old (≥18 mo) c57bl/6 mice with the murine γherpesvirus 68. acute murine γherpesvirus 68 infection in aging mice resulted in severe pneumonitis and fibrosis compared with young animals. progressive clinical deterioration and lung fibrosis in th ... | 2012 | 22227563 |
| unsupervised learning techniques reveal heterogeneity in memory cd8(+) t cell differentiation following acute, chronic and latent viral infections. | cd8(+) t lymphocytes are critical for the control of gammaherpesvirus latency. to determine how memory cd8(+) t cells generated during latency differ from those primed during acute or chronic viral infection, we adoptively transferred naive p14 cd8(+) t cells into uninfected recipients, and examined surface proteins, cytokines and transcription factors following infection with the armstrong (acute) or clone 13 (chronic) strains of lymphocytic choriomeningitis virus (lcmv), or murine gammaherpesv ... | 2017 | 28689040 |
| transformation of cells by photoinactivated murine gamma-herpesvirus 68 during nonproductive and quiescent infection. | infection of human mrc-5 cells and mouse nih-3t3 cells with a murine gamma-herpesvirus (muhv-4 strain 68; mhv-68) photoinactivated by visible light in the presence of methylene blue (mb) resulted in nonproductive infection and the appearance of morphologically transformed cells. two stably transformed cell lines were derived from both of these cell types and were confirmed to contain both viral dna and antigen. next, a quiescent mhv-68 infection in mrc-5 and nih-3t3 cells was established after c ... | 2017 | 28848176 |
| the replication and transcription activator of murine gammaherpesvirus 68 cooperatively enhances cytokine-activated, stat3-mediated gene expression. | gammaherpesviruses (γηvs) have a dynamic strategy for life-time persistence, involving productive infection, latency, and intermittent reactivation. in latency reservoirs, such as b lymphocytes, γηv exists as a viral episome and expresses few viral genes. although the ability of γhv to reactivate from latency and re-enter the lytic phase is challenging to investigate and control, it is known that the γηv replication and transcription activator, rta, can promote lytic reactivation. in this study, ... | 2017 | 28821622 |
| murine gammaherpesvirus m2 antigen modulates splenic b cell activation and terminal differentiation in vivo. | murine gammaherpesvirus 68 (mhv68) infection of laboratory strains of mice has provided a tractable small animal model for dissecting gammaherpesvirus pathogenesis. the mhv68 latency associated antigen m2 promotes viral latency establishment in germinal center (gc) b cells and plays an important role in virus infection of plasma cells (pcs), which is linked to virus reactivation. more recently, m2 has been highlighted as a potent immunomodulatory molecule capable of hindering both cell-mediated ... | 2017 | 28767707 |
| mhv68 expressing kshv lana reveals both functional conservation and divergence in lana homologs. | latency-associated nuclear antigen (lana) is a multifunctional protein encoded by members of the rhadinovirus genus of gammaherpesviruses. studies using murine gammaherpesvirus 68 (mhv68) demonstrated that lana is important for acute replication, latency establishment, and reactivation in vivo despite structural similarities in their dna-binding domains (dbds), lana homologs from kaposi sarcoma-associated herpesvirus (kshv) and mhv68 exhibit considerable sequence divergence. we sought to determi ... | 2017 | 28747501 |
| the major envelope glycoprotein of murid herpesvirus 4 promotes sexual transmission. | gammaherpesviruses are important human and animal pathogens. infection control has proven difficult because the key process of transmission is ill understood. murid herpesvirus 4 (muhv-4), a gammaherpesvirus of mice, is transmitted sexually. we show that this depends on the major virion envelope glycoprotein gp150. gp150 is redundant for host entry, and in vitro, it regulates rather than promotes cell binding. we show that gp150-deficient muhv-4 reaches and replicates normally in the female geni ... | 2017 | 28424280 |
| cd8+ t cell evasion mandates cd4+ t cell control of chronic gamma-herpesvirus infection. | gamma-herpesvirus infections are regulated by both cd4+ and cd8+ t cells. however clinical disease occurs mainly in cd4+ t cell-deficient hosts. in cd4+ t cell-deficient mice, cd8+ t cells control acute but not chronic lung infection by murid herpesvirus-4 (muhv-4). we show that acute and chronic lung infections differ in distribution: most acute infection was epithelial, whereas most chronic infection was in myeloid cells. cd8+ t cells controlled epithelial infection, but cd4+ t cells and ifnγ ... | 2017 | 28394921 |
| gamma-herpesvirus colonization of the spleen requires lytic replication in b cells. | gamma-herpesviruses infect lymphocytes and cause lymphocytic cancers. murid herpesvirus-4 (muhv-4), epstein-barr virus and the kaposi's sarcoma-associated herpesvirus all infect b cells. latent infection can spread by b cell recirculation and proliferation, but whether this alone achieves systemic infection is unclear. to test the need of muhv-4 for lytic infection in b cells we flanked its essential orf50 lytic transactivator with loxp sites, then infected mice with b cell-specific cre expressi ... | 2018 | 29343572 |
| tick-borne transmission of murine gammaherpesvirus 68. | herpesviruses are a large group of dna viruses infecting mainly vertebrates. murine gammaherpesvirus 68 (mhv68) is often used as a model in studies of the pathogenesis of clinically important human gammaherpesviruses such as epstein-barr virus and kaposi's sarcoma-associated herpesvirus. this rodent virus appears to be geographically widespread; however, its natural transmission cycle is unknown. following detection of mhv68 in field-collected ticks, including isolation of the virus from tick sa ... | 2017 | 29164067 |
| murine gammaherpesvirus 68: a small animal model for gammaherpesvirus-associated diseases. | murine gammaherpesvirus 68 (mhv68) is a naturally occurring pathogen of murid rodents that is genetically related to the human gammaherpesviruses epstein-barr virus (ebv) and kaposi sarcoma-associated herpesvirus (kshv). viral, immunologic, and disease parameters following experimental infection of laboratory mice with mhv68 closely resemble what occurs during primary ebv infection of humans, which suggests that mhv68 infection of mice offers a small animal model to study in general the pathogen ... | 2017 | 29052141 |
| epstein-barr virus bkrf4 gene product is required for efficient progeny production. | epstein-barr virus (ebv), a member of human gammaherpesvirus, infects mainly b cells. ebv has two alternative life cycles, latent and lytic, and is reactivated occasionally from the latent stage to the lytic cycle. to combat ebv-associated disorders, understanding the molecular mechanisms of the ebv lytic replication cycle is also important. here, we focused on an ebv lytic gene, bkrf4. using our anti-bkrf4 antibody, we revealed that the bkrf4 gene product is expressed during the lytic cycle wit ... | 2017 | 28904200 |
| antiviral activity of 20(r)-ginsenoside rh2 against murine gammaherpesvirus. | ginsenosides are the major components of panax ginseng meyer, an herbal medicine used for the treatment of various diseases. different ginsenosides contribute to the biological properties of ginseng, such as antimicrobial, anticancer, and immunomodulatory properties. in this study, we investigated the antiviral effects of 15 ginsenosides and compound k on gammaherpesvirus. | 2017 | 29021696 |
| conditional mutagenesis in vivo reveals cell type- and infection stage-specific requirements for lana in chronic mhv68 infection. | gammaherpesvirus (ghv) pathogenesis is a complex process that involves productive viral replication, dissemination to tissues that harbor lifelong latent infection, and reactivation from latency back into a productive replication cycle. traditional loss-of-function mutagenesis approaches in mice using murine gammaherpesvirus 68 (mhv68), a model that allows for examination of ghv pathogenesis in vivo, have been invaluable for defining requirements for specific viral gene products in ghv infection ... | 2018 | 29364981 |
| first detection of murine herpesvirus 68 in adult ixodes ricinus ticks. | murine herpesvirus 68 (mhv-68) is a natural pathogen that infects murid rodents, which serves as hosts for ixodes ricinus ticks. for the first time, mhv-68 was detected in immature i. ricinus ticks feeding on lacerta viridis lizards trapped in slovakia, which supports the idea that ticks can acquire the virus from feeding on infected hosts. the recent discovery of mhv-68 infection and mhv-68 m3 gene transcripts in dermacentor reticulatus ticks collected in slovakia also supports this suggestion. ... | 2018 | 29352410 |
| regulation of gammaherpesvirus lytic replication by endoplasmic reticulum stress-induced transcription factors atf4 and chop. | the stress-induced unfolded protein response (upr) in the endoplasmic reticulum (er) involves various signaling crosstalks and controls cell fate. b-cell receptor (bcr) signaling, which can trigger upr, induces gammaherpesvirus lytic replication and serves as a physiological mechanism for gammaherpesvirus reactivation in vivo. however, how the upr regulates bcr-mediated gammaherpesvirus infection is unknown. here, we demonstrate that the er stressors tunicamycin and thapsigargin inhibit bcr-medi ... | 2018 | 29305424 |
| host tumor suppressor p18ink4c functions as a potent cell-intrinsic inhibitor of γhv68 reactivation and pathogenesis. | gammaherpesviruses are common viruses associated with lifelong infection and increased disease risk. reactivation from latency aids the virus in maintaining infection throughout the life of the host and is responsible for a wide array of disease outcomes. previously, we demonstrated that the virus encoded cyclin (v-cyclin) of murine gammaherpesvirus 68 (γhv68) is essential for optimal reactivation from latency in normal mice but not in mice lacking the host tumor suppressor, p18ink4c (p18). whet ... | 2018 | 29298882 |
| recognizing the sines of infection: regulation of retrotransposon expression and modulation of host cell processes. | short interspersed elements (sines) are a family of retrotransposons evolutionarily derived from cellular rna polymerase iii transcripts. over evolutionary time, sines have expanded throughout the human genome and today comprise ~11% of total chromosomal dna. while generally transcriptionally silent in healthy somatic cells, sine expression increases during a variety of types of stresses, including dna virus infection. the relevance of sine expression to viral infection was largely unexplored, h ... | 2017 | 29258254 |
| a gammaherpesvirus provides protection against allergic asthma by inducing the replacement of resident alveolar macrophages with regulatory monocytes. | the hygiene hypothesis postulates that the recent increase in allergic diseases such as asthma and hay fever observed in western countries is linked to reduced exposure to childhood infections. here we investigated how infection with a gammaherpesvirus affected the subsequent development of allergic asthma. we found that murid herpesvirus 4 (muhv-4) inhibited the development of house dust mite (hdm)-induced experimental asthma by modulating lung innate immune cells. specifically, infection with ... | 2017 | 29035391 |
| cross-species conservation of episome maintenance provides a basis for in vivo investigation of kaposi's sarcoma herpesvirus lana. | many pathogens, including kaposi's sarcoma herpesvirus (kshv), lack tractable small animal models. kshv persists as a multi-copy, nuclear episome in latently infected cells. kshv latency-associated nuclear antigen (klana) binds viral terminal repeat (ktr) dna to mediate episome persistence. model pathogen murine gammaherpesvirus 68 (mhv68) mlana acts analogously on mtr dna. klana and mlana differ substantially in size and ktr and mtr show little sequence conservation. here, we find klana and mla ... | 2017 | 28910389 |
| type i interferon signaling to dendritic cells limits murid herpesvirus 4 spread from the olfactory epithelium. | murid herpesvirus 4 (muhv-4) is a b cell-tropic gammaherpesvirus that can be studied in vivo despite viral evasion, type i interferons (ifn-i) limit its spread. after muhv-4 inoculation into footpads, ifn-i protect lymph node subcapsular sinus macrophages (ssm) against productive infection; after peritoneal inoculation, they protect splenic marginal zone macrophages, and they limit muhv-4 replication in the lungs. while invasive infections can be used to test specific aspects of host colonizatio ... | 2017 | 28904198 |
| common vole (microtus arvalis) and bank vole (myodes glareolus) derived permanent cell lines differ in their susceptibility and replication kinetics of animal and zoonotic viruses. | pathogenesis and reservoir host adaptation of animal and zoonotic viruses are poorly understood due to missing adequate cell culture and animal models. the bank vole (myodes glareolus) and common vole (microtus arvalis) serve as hosts for a variety of zoonotic pathogens. for a better understanding of virus association to a putative animal host, we generated two novel cell lines from bank voles of different evolutionary lineages and two common vole cell lines and assayed their susceptibility, rep ... | 2019 | 31513859 |
| birds belonging to the family paridae as another potential reservoir of murine gammaherpesvirus 68. | ecology and epidemiology of murine gammaherpesvirus 68 (mhv-68) have been intensively studied since the isolation of the virus from murid rodents in 1976. this virus was detected in various mammalian species that share the biotope with rodent reservoirs of mhv-68. however, a survey of mhv-68 in birds has not so far been performed. therefore, the aim of this study was to investigate the presence of mhv-68 in blood samples from two bird species captured at four localities in slovakia. using the ne ... | 2021 | 34339313 |