Publications

murine gammaherpesvirus 68: a model for the study of gammaherpesvirus pathogenesis.	murine gammaherpesvirus 68 (mhv-68) is a naturally occurring herpesvirus of wild rodents and is genetically related to human herpesvirus 8 and epstein-barr virus. the ability of mhv-68 to establish acute and persistent infection within laboratory mice offers a unique opportunity to investigate immunological and virological aspects of gammaherpesvirus pathogenesis.	1998	9717216
kinetic analysis of the specific host response to a murine gammaherpesvirus.	respiratory infection of balb/c mice with the murine gammaherpesvirus 68 (mhv-68) induces the clonal expansion of virus-specific cytotoxic t-lymphocyte (ctl) precursors (ctlp) in the regional, mediastinal lymph nodes (mln). some of these ctlps differentiate to become fully functional ctl effectors, which can be detected in both the lymphoid tissue and in the site of pathology in the lung. though the lymph nodes and spleen harbor substantial populations of latently infected b cells for life, the ...	1998	9444986
lung epithelial cells are a major site of murine gammaherpesvirus persistence.	it is currently believed that latently infected, resting b lymphocytes are central to gammaherpesvirus persistence, whereas mucosal epithelial cells are considered nonessential. we have readdressed the question of nonlymphoid persistence using murine gammaherpesvirus 68 (mhv-68). to dissect lymphoid from nonlymphoid persistence, we used micromt transgenic mice that are defective in b cells. mhv-68 dna persisted in the lungs of intact and b cell-deficient mice. both episomal and linear forms of t ...	1998	9625754
four trna-like sequences and a serpin homologue encoded by murine gammaherpesvirus 68 are dispensable for lytic replication in vitro and latency in vivo.	experimental infection of inbred strains of laboratory mice with murine herpesvirus 68 (mhv-68), a natural pathogen of wild rodents, results in acute productive infection of the lung followed by a latent infection of b lymphocytes. we have previously shown that mhv-68 encodes an open reading frame with similarity to poxvirus serpins, designated orf1, and eight novel trna-like sequences. the latter are processed into mature, uncharged trnas and are abundantly expressed during both lytic and laten ...	1998	9460936
pathogenesis of murine gammaherpesvirus-68 infection in interleukin-6-deficient mice.	murine gammaherpesvirus-68 (mhv-68) induces high levels of interleukin (il)-6 production in both naive and primed lymphocyte populations. mice that are homozygous (-/-) for deletion of the il-6 gene were used to investigate the role of this cytokine in mhv-68 infection. the results showed that il-6 is not essential for clearance of infectious mhv-68 from the lung or for the establishment, or control, of viral latency. both il-6 +/+ and -/- mice eliminated replicating virus from the respiratory t ...	1998	9791027
lymphoproliferative disease induced by murine herpesvirus-68.		1998	10090040
complete sequence and genomic analysis of murine gammaherpesvirus 68.	murine gammaherpesvirus 68 (gammahv68) infects mice, thus providing a tractable small-animal model for analysis of the acute and chronic pathogenesis of gammaherpesviruses. to facilitate molecular analysis of gammahv68 pathogenesis, we have sequenced the gammahv68 genome. the genome contains 118,237 bp of unique sequence flanked by multiple copies of a 1,213-bp terminal repeat. the gc content of the unique portion of the genome is 46%, while the gc content of the terminal repeat is 78%. the uniq ...	1997	9223479
gamma interferon is not essential for recovery from acute infection with murine gammaherpesvirus 68.	murine gammaherpesvirus 68 (mhv-68) when administered intranasally induces high levels of gamma interferon (ifn-gamma) in the lymphoid tissues of infected mice. in order to investigate the role of this cytokine in the immune response to mhv-68, mice which were congenitally deficient in the ifn-gamma gene (ifn-gamma knockout mice) were infected with the virus. comparison of the courses of the disease in wild-type control and ifn-gamma knockout mice revealed surprisingly little difference. both gr ...	1997	9094668
genetic content and preliminary transcriptional analysis of a representative region of murine gammaherpesvirus 68.	murine gammaherpesvirus 68 (mhv-68) is a relatively recently discovered pathogen of wild rodents and provides a unique opportunity to explore in detail the interactions of a gammaherpesvirus with its natural host. it may also provide a much needed small animal model for human gammaherpesviruses. as a step in the detailed analysis of virus gene structure and expression we have sequenced over 20 kb of the mhv-68 genome and mapped gene transcripts by northern blot hybridization. the region we chose ...	1997	9191940
glycoprotein b of bovine herpesvirus 4 is a major component of the virion, unlike that of two other gammaherpesviruses, epstein-barr virus and murine gammaherpesvirus 68.	this study reports that in bovine herpesvirus 4, glycoprotein b (gb) is a heterodimer and a major component of the virion, unlike gbs of epstein-barr virus (gp110) and murine gammaherpesvirus 68, two other gammaherpesviruses. these are new characteristics with regard to the general features of gb in the gammaherpesvirinae subfamily.	1997	9060705
identification of ovine herpesvirus-2 infection in sheep.	a polymerase chain reaction test for the detection of ovine herpesvirus-2 (ohv-2) dna was used to identify sites of ohv-2 infection in peri-natal lambs and in adult sheep. ohv-2 was detected in the nasal secretions from all lambs within a period of two months following birth. subsequently, ohv-2 dna was identified in a number of epithelial tissues including the cornea, turbinates and pharynx. in addition, ohv-2 dna was detected exclusively in b-lymphocytes from six of ten adult sheep tested. an ...	1997	9170507
pathological changes in the spleens of gamma interferon receptor-deficient mice infected with murine gammaherpesvirus: a role for cd8 t cells.	murine gammaherpesvirus is a natural rodent pathogen which causes a primary infection in the lungs and establishes a persistent infection in b lymphocytes. during the primary infection, large amounts of gamma interferon (ifn-gamma) are produced by spleen, mediastinal, and cervical lymph node cells. to investigate the role of ifn-gamma in control of the virus infection, mice lacking the cellular receptor for ifn-gamma (ifn-gamma r-/- mice) were infected with murine gammaherpesvirus 68 (mhv68). if ...	1997	9151815
murine gammaherpesvirus 68 encodes trna-like sequences which are expressed during latency.	murine gammaherpesvirus 68 (mhv-68) is a virus of wild rodents and is a convenient small animal model for studies of gammaherpesvirus pathogenesis. we have sequenced 6162 bp at the left end of the mhv-68 genome and identified two unique open reading frames (orfs) (orf2 and orf3) and an orf (orf1) which displays similarity to poxvirus members of the serpin family. interspersed with the orfs is a family of eight novel trna-like sequences sharing trna-like predicted secondary structures and rna pol ...	1997	9225045
identification and characterization of murine gammaherpesvirus 68 gp150: a virion membrane glycoprotein.	murine gammaherpesvirus 68 (mhv-68) is a naturally occurring virus of murid rodents which displays pathobiological characteristics similar to those of other gammaherpesviruses, including epstein-barr virus (ebv). however, unlike ebv and many other gammaherpesviruses, mhv-68 replicates in epithelial cells in vitro and infects laboratory strains of mice and therefore provides a good model for the study of gammaherpesviruses. studies of sequences around the center of the mhv-68 genome identified a ...	1996	8648686
cytokine production in the immune response to murine gammaherpesvirus 68.	cytokine profiles were determined following intranasal infection of c57bl/6j mice with murine gammaherpesvirus 68 (mhv-68). spleen, mediastinal, and cervical lymph node cells from infected mice produced high levels of interleukin 6 (il-6) and gamma interferon (ifn-gamma) and lower levels of il-2 and il-10 following in vitro restimulation. little or no il-4 or il-5 was detected. cytokine production was generally maximal at 10 days after infection, correlating with viral clearance from the lung, a ...	1996	8627809
murine gammaherpesvirus-68 encodes homologues of thymidine kinase and glycoprotein h: sequence, expression, and characterization of pyrimidine kinase activity.	we have sequenced a 4.5-kb fragment of dna spanning the junction of the bamhi d and e fragments of murine gammaherpesvirus-68 (mhv-68). this sequence was found to code for two major open reading frames (orfs) of 1934 and 2192 bp which showed significant homology to the thymidine kinase (tk) and glycoprotein h (gh) sequences of other gammaherpesviruses. upstream from the tk gene another orf was found which showed amino acid sequence homology to the hsv1 ul24 gene. analysis of the 1934-bp orf reve ...	1996	8638414
mature b cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68.	murine gammaherpesvirus 68 (gamma hv-68; also referred to as mhv-68) is a gammaherpesvirus which infects murid rodents. previous studies showed that cd8 t cells are important for controlling gamma hv-68 replication during the first 2 weeks of infection and suggested a role for b cells in latent or persistent gamma hv-68 infection. to further define the importance of b cells and cd8 t cells during acute and chronic gamma hv-68 infection, we examined splenic infection in mice with null mutations i ...	1996	8794315
characterization of tumor cell lines derived from murine gammaherpesvirus-68-infected mice.	cell lines were derived from mice with murine gammaherpesvirus-68 (mhv-68)-associated lymphoproliferative disease. four were of an ambiguous phenotype and were mhv-68 negative. one, s11, was a b lymphocyte that contained mhv-68 genomes in both linear and episomal forms and released virus. the line was clonable and grew into tumors in nude mice. this is the first naturally occurring mhv-68-positive b-cell line to be generated, and it will be an invaluable tool for the study of mhv-68 latency.	1996	8709292
progressive loss of cd8+ t cell-mediated control of a gamma-herpesvirus in the absence of cd4+ t cells.	a unique experimental model has been developed for dissecting the integrity of cd8+ t cell-mediated immunity to a persistent gammaherpesvirus under conditions of cd4+ t cell deficiency. respiratory challenge of major histocompatibility complex class ii -/- and +/+ c57bl/6j mice with the murine gammaherpesvirus 68 (mhv-68) leads to productive infection of both lung and adrenal epithelial cells. virus titers peak within 5-10 d, and are no longer detected after day 15. persistent, latent infection ...	1996	9064346
absence of splenic latency in murine gammaherpesvirus 68-infected b cell-deficient mice.	murine gammaherpesvirus 68 (mhv-68) is a natural pathogen of mice which causes an acute lung infection and establishes a latent infection in b lymphocytes. in this paper we describe the infection in transgenic b cell-deficient (mumt) mice, to determine whether a latent infection can be established in a mouse lacking circulating b lymphocytes. little difference was observed in the acute lung infection, although there was a slight delay in virus clearance in the mumt mice. this indicates that anti ...	1996	8922476
lymphoproliferative disease in mice infected with murine gammaherpesvirus 68.	murine gammaherpesvirus is a natural pathogen of wild rodents. in the laboratory it establishes an infection of epithelial cells and persists in b lymphocytes in a latent form. inbred mice chronically infected with the virus develop a lymphoproliferative disease (lpd) similar to that seen in patients infected with epstein-barr virus. the frequency of lpd over a period of 3 years was 9% of all infected animals, with 50% of these displaying high grade lymphomas. the incidence of lpd was greatly in ...	1994	7943173
characterization of murine gammaherpesvirus 68 glycoprotein b (gb) homolog: similarity to epstein-barr virus gb (gp110).	murine gammaherpesvirus 68 (mhv-68) is a natural pathogen of murid rodents and displays similar pathobiological characteristics to those of the human gammaherpesvirus epstein-barr virus (ebv). however, in contrast to ebv, mhv-68 will replicate in epithelial cells in vitro. it has therefore been proposed that mhv-68 may be of use as a model for the study of gammaherpesviruses, ebv in particular, both in vitro and in vivo. the ebv homolog of herpes simplex virus glycoprotein b (gb), termed gp110, ...	1994	8083987
interactions of the murine gammaherpesvirus with the immune system.	our understanding of the host response to gammaherpesviruses comes largely from studies on epstein-barr virus. a recent addition to this family is murine herpesvirus-68 which, like epstein-barr virus, establishes a latent infection in b lymphocytes and is associated with lymphoproliferative disease. this virus provides a unique opportunity to explore the relationship between gammaherpesviruses and the immune system.	1994	7946042
interactions of murine gammaherpesvirus 68 with b and t cell lines.	murine gammaherpesvirus is a natural pathogen of wild rodents. we have established that in vivo the virus persists in b lymphocytes in a latent form and therefore has similar biological properties to epstein-barr virus and related gamma-i-herpesviruses. in this report we have established a persistent infection in mouse myeloma (b) cells (nso cell line), but not in mouse thymoma (t) cells (bw 5147 cell line). the virus persists indefinitely in myeloma cells, without any apparent cytopathic effect ...	1993	8460488
pathogenesis of murine gammaherpesvirus infection in mice deficient in cd4 and cd8 t cells.	murine gammaherpesvirus is a natural pathogen of wild mice. the virus infects alveolar cells and spleen cells during the primary infection and establishes a latent/persistent infection in b lymphocytes. little is known about the immunological response to gammaherpesviruses during a primary infection. to address this issue, we investigated the pathogenesis of murine herpesvirus 68 (mhv-68) infection in mice deficient in cd4 or cd8 t-cell populations. infection of the lung and spleen were greatly ...	1993	8394447
virological and pathological features of mice infected with murine gamma-herpesvirus 68.	the primary infection of balb/c mice with murine herpesvirus 68 (mhv-68) was investigated. when the virus was introduced intranasally, the lung was the main tissue infected, the virus being associated with alveolar epithelium and mononuclear cells. a productive infection lasted for 10 days, after which viral dna could be detected by in situ hybridization up to 30 days after infection. at that time lymphoproliferative accumulations were also observed in the lung, with formation of germinal centre ...	1992	1328491
murine gammaherpesvirus 68 establishes a latent infection in mouse b lymphocytes in vivo.	murine gammaherpesvirus 68 (mhv-68) is able to persist in spleen cells of infected mice. to determine the cell type harbouring persistent virus, spleen cells from infected animals were separated into immunoglobulin (ig)-positive (b cell-enriched), ig-negative (t cell-enriched) and plastic-adherent (macrophage-enriched) fractions. these cells were co-cultivated with permissive bhk-21 cells in an infectious centre assay. the consistent recovery and enrichment of infectious centres in the ig-positi ...	1992	1469366
cloning and molecular characterization of the murine herpesvirus 68 genome.	murine herpesvirus 68 (mhv-68) is a naturally occurring herpesvirus of small free-living rodents. in order to facilitate the molecular characterization of the virus genome, a library of cloned restriction fragments has been produced and restriction enzyme cleavage maps deduced for the enzymes bamhi, ecori and hindiii. the mhv-68 genome comprises a region of unique dna of approximately 118 kbp which is flanked by variable numbers of a 1.23 kb repeat unit. the organization of the mhv-68 genome is, ...	1990	2351958
murine herpesvirus 68 is genetically related to the gammaherpesviruses epstein-barr virus and herpesvirus saimiri.	short nucleotide sequence analysis of seven restriction fragments of murine herpesvirus 68 (mhv-68) dna has been undertaken and used to determine the overall genome organization and relatedness of this virus to other well characterized representatives of the alpha-, beta- and gammaherpesvirus subgroups. nine genes have been identified which encode amino acid sequences with greater similarity to proteins of the gammaherpesvirus epstein-barr virus (ebv) than to the homologous products of the alpha ...	1990	2161903
autophagy genes enhance murine gammaherpesvirus 68 reactivation from latency by preventing virus-induced systemic inflammation.	host genes that regulate systemic inflammation upon chronic viral infection are incompletely understood. murine gammaherpesvirus 68 (mhv68) infection is characterized by latency in macrophages, and reactivation is inhibited by interferon-γ (ifn-γ). using a lysozyme-m-cre (lysmcre) expression system, we show that deletion of autophagy-related (atg) genes fip200, beclin 1, atg14, atg16l1, atg7, atg3, and atg5, in the myeloid compartment, inhibited mhv68 reactivation in macrophages. atg5 deficiency ...	0	26764599