Mouse strains are either resistant or susceptible to murine cytomegalovirus (MCMV). Resistance is determined by the Cmv1(r) (Ly49h) gene, which encodes Ly49H NK cell activation receptor. The protein encoded m157 gene of MCMV has been defined as a ligand for Ly49H. To find out whether only MCMV, we constructed deletion mutant and revertant virus. Viruses were tested susceptibility control in Ly49H+ Ly49H- mouse strains. Deletion abolished viral cells, resulting higher virus virulence vivo....

ABSTRACT Human cytomegalovirus (HCMV), a ubiquitous human pathogen, is the leading cause of birth defects and morbidity in immunocompromised patients potential trigger for vascular disease. HCMV replicates endothelial cells drives leukocyte-mediated viral dissemination through close endothelium- leukocyte interaction. However, genetic basis growth transfer to leukocytes unknown. We show here that UL131-128 gene locus indispensable both productive infection transmission leukocytes. The...

Abstract CD8+ T lymphocytes play an important role in the control of intracellular pathogens during both acute and persistent infections. This is particularly true case herpesviruses such as human CMV, which are typified by large virus-specific cell populations viral latency. To understand origin these factors shaping them over time, we investigated response after murine CMV (MCMV) infection. The kinetics were characterized rapid expansion activated cells, followed a contraction phase....

ABSTRACT Gammaherpesviruses cause important infections of humans, in particular immunocompromised patients. Recently, murine gammaherpesvirus 68 (MHV-68) infection mice has been developed as a small animal model pathogenesis. Efficient generation mutants MHV-68 would significantly contribute to the understanding viral gene functions virus-host interaction, thereby further enhancing potential this model. To end, we cloned genome bacterial artificial chromosome (BAC) Escherichia coli . During...

Recently the mouse cytomegalovirus (MCMV) genome was cloned as an infectious bacterial artificial chromosome (BAC) (M. Messerle, I. Crnkovic, W. Hammerschmidt, H. Ziegler, and U. Koszinowski, Proc. Natl. Acad. Sci. USA 94:14759-14763, 1997). The virus obtained from this construct is attenuated in vivo due to deletion of viral sequences insertion BAC vector. We reconstituted full-length MCMV flanked vector with identical sequences. This new represents a versatile basis for construction...

The passage of large-sized herpesviral capsids through the nuclear lamina and inner membrane to leave nucleus requires a dissolution lamina. Here, we report on functions M50/p35, β-herpesviral protein murine cytomegalovirus. M50/p35 inserts into is aggregated by second viral protein, M53/p38, form capsid docking site. recruits cellular kinase C for phosphorylation lamina, suggesting that herpesviruses target critical element architecture.

Cellular receptors for the Fc domain of immunoglobulin G (IgG) (FcgammaRs) comprise a family surface on immune cells connecting humoral and cellular responses. Several herpesviruses induce FcgammaR activities in infected cells. Here we identify two distinct human cytomegalovirus (HCMV)-encoded vFcgammaR glycoproteins 34 68 kDa. A panel HCMV strains exhibited slight molecular microheterogeneity between Fcgamma-binding proteins, suggesting their viral origin. To locate responsible genes within...

Cytomegaloviruses (CMVs) deploy a set of genes for interference with antigen presentation in the major histocompatibility complex (MHC) class I pathway. In murine CMV (MCMV), three were identified so far: m04/gp34, m06/gp48, and m152/gp40. While their function as immunoevasins was originally defined after selective expression, this may not necessarily reflect biological role during infection. The might act synergistically, but they also compete common substrate, MHC complexes. To approach...

The large cytomegalovirus (CMV) US22 gene family, found in all betaherpesviruses, comprises 12 members both human (HCMV) and murine (MCMV). Conserved sequence motifs suggested a common ancestry related functions for these products. Two of this m140 m141, were recently shown to affect MCMV replication on macrophages. To test the role cell tropism, we analyzed growth properties different types mutants carrying transposon insertions family members. When necessary, additional targeted with...

A mouse cytomegalovirus (MCMV) gene conferring interferon (IFN) resistance was identified. This gene, M27, encodes a 79-kD protein that selectively binds and down-regulates for signal transducer activator of transcription (STAT)-2, but it has no effect on STAT1 activation signaling. The absence pM27 conferred MCMV susceptibility to type I IFNs (α/β), had much more dramatic II (γ) in vitro vivo. comparative analysis M27+ M27− revealed the antiviral efficiency IFN-γ partially dependent...

ABSTRACT Proteins associated with the murine cytomegalovirus (MCMV) viral particle were identified by a combined approach of proteomic and genomic methods. Purified MCMV virions dissociated complete denaturation subjected to either separation sodium dodecyl sulfate-polyacrylamide gel electrophoresis in-gel digestion or treated directly in-solution tryptic digestion. Peptides separated nanoflow liquid chromatography analyzed tandem mass spectrometry (LC-MS/MS). The MS/MS spectra obtained...

Cytomegaloviruses (CMVs) code for several proteins that inhibit the presentation of antigenic peptides to CD8 T cells. Although molecular mechanisms CMV interference with major histocompatibility complex class I pathway are long understood, surprisingly little evidence exists support a role in vivo. Here we document first example an peptide being blocked by immune evasion protein organs relevant disease. this Db-restricted peptide, which is derived from antiapoptotic M45 murine (mCMV),...

ABSTRACT CD8 + T cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis C Epstein-Barr and cytomegalovirus (CMV). In most large -T-cell populations induced early but then contract maintained thereafter at lower levels. contrast, specific murine CMV (MCMV) have been shown to gradually accumulate after resolution primary infection. This unique behavior is restricted certain epitopes, including an immunodominant epitope derived...

Both human cytomegaloviruses (HCMVs) and murine (MCMVs) encode multiple genes that interfere with antigen presentation by major histocompatibility complex (MHC) class I, thus protect infected targets from lysis virus-specific cytotoxic T lymphocytes (CTLs). HCMV has been shown to four such MCMV two. m152 blocks the export of I a pre-Golgi compartment, m6 directs lysosome for degradation. A third gene, m4, encodes glycoprotein which is expressed at cell surface in association I. Here we here...

Abstract Although in vitro studies have shown that herpesviruses, including murine CMV (MCMV), encode genes interfere with the MHC class I pathway, their effects on CTL response vivo is unclear. We identified a Db-restricted epitope from MCMV M45 by screening an genomic library using clones isolated mice infected lacking m152. Because m152 severely inhibits recognition of vitro, we questioned whether M45-specific would be generated wild-type expressing Mice or MCMVΔm152 made similar...

Essential viral proteins perform vital functions during morphogenesis via a complex interaction with other and cellular gene products. Here, we present novel approach to comprehensive mutagenesis of essential cytomegalovirus genes biological analysis in the 230-kbp-genome context. A random Tn7-based procedure at single-gene level was combined site-specific recombination FLP/FLP recognition target site system for genome reconstitution. We show function more than 100 mutants from larger...

Abstract As with most herpesviruses, CMVs encode viral genes that inhibit Ag presentation to CD8 T cells (VIPRs). VIPR function has been assumed be essential for CMV establish its characteristic lifetime infection of host. We compared C57BL/6 mice wild-type murine (MCMV) and a virus lacking each MCMV’s three known VIPRs: m4, m6, m152. During acute infection, there was very little difference between the two viruses respect kinetics replication clearance, or in size virus-specific cell...

ABSTRACT Murine cytomegalovirus encodes three regulators of antigen presentation to antiviral CD8 T cells. According current paradigms, all are committed the inhibition antigenic peptides. Whereas m152/gp40 catalyzes retention peptide-loaded major histocompatibility complex (MHC) class I molecules in a cis -Golgi compartment, m06/gp48 binds stably and directs them into cellular cargo-sorting pathway lysosomal degradation. Regulator m04/gp34 also molecules, but unlike m152 m06, it does not...

MHC class I and II molecules are essential for intrathymic maturation of a normal repertoire alpha beta T cells. The development gamma delta cells may similarly require exposure to conventional or MHC-like appropriate negative positive selection. availability mice that devoid cell surface expression allowed us test directly the hypothesis play role in proportions thymus, lymph nodes, spleens were indistinguishable between II-deficient littermate controls by FACS analysis. from proliferated...

The role of the products UL10 and UL49.5 homologous genes Marek's disease virus serotype 1 (MDV-1) in replication was investigated. Deletion either open reading frame an infectious bacterial artificial chromosome clone (BAC20) MDV-1 resulted progeny viruses that were unable to spread from cell cell. After transfection UL10- or UL49.5-negative BAC20 DNA into chicken quail cells, only single infected cells observed by indirect immunofluorescence analysis. In contrast, plaque formation restored...

We and others have shown that infection of dendritic cells with murine cytomegalovirus (MCMV) leads to severe functional impairment these antigen-presenting (D. M. Andrews, C. E. Andoniou, F. Granucci, P. Ricciardi-Castagnoli, A. Degli-Esposti, Nat. Immunol. 2:1077-1084, 2001; S. Mathys, T. Schroeder, J. Ellwart, U. H. Koszinowski, Messerle, Just, Infect. Dis. 187:988-999, 2003). Phenotypically, reduced surface expression costimulatory molecules major histocompatibility complex was detected....