nanoString evaluation of murine Cytomegalovirus transcription in vivo and in vitro

2021 ◽  
pp. 114436
Author(s):  
Marion Griessl ◽  
Michael Gutknecht ◽  
Vanda Juranic-Lisnic ◽  
Charles H. Cook
Keyword(s):  
Murine Cytomegalovirus

A Novel Peptide Aldehyde with Activity against Human Cytomegalovirus in Two Different in Vivo Models

2000 ◽  
Vol 11 (1) ◽  
pp. 51-59 ◽  
Author(s):  
Olaf Weber ◽  
Jürgen Reefschläger ◽  
Helga Rübsamen-Waigmann ◽  
Siegfried Raddatz ◽  
Matthias Hesseling ◽  
...  
Keyword(s):  
Animal Models ◽  
Antiviral Activity ◽  
Clinical Isolate ◽  
Human Cytomegalovirus ◽  
Murine Cytomegalovirus ◽  
Human Tissues ◽  
In Vivo Models ◽  
Peptide Aldehydes

Novel peptide aldehydes (PAs) were identified as potent inhibitors of human cytomegalovirus (HCMV) in vitro. Although these compounds were highly effective against HCMV, they did not exhibit any activity against murine cytomegalovirus (MCMV). The purpose of this study was to test the antiviral activity of PA 8 as a representative of this novel class of inhibitors against HCMV in vivo. Because of the strict species specificity of HCMV we had to use two artificial animal models. In the first model, HCMV-infected human cells were entrapped into agarose plugs and transplanted into mice. In the second model, SCID mice were transplanted with human tissues that were subsequently infected with a clinical isolate of HCMV. In these two models the antiviral activity of PA 8 was clearly demonstrated, ganciclovir only being slightly superior in its in vivo antiviral activity.

scholarly journals Adoptive transfer of anti-cytomegalovirus effect of interleukin-2- activated bone marrow: potential application in transplantation

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 720-727 ◽  
Author(s):  
R Agah ◽  
BS Charak ◽  
V Chen ◽  
A Mazumder
Keyword(s):  
Bone Marrow ◽  
Interleukin 2 ◽  
Murine Cytomegalovirus ◽  
Mcmv Infection ◽  
Murine Bone Marrow ◽  
Therapeutic Setting ◽  
Infected Cells ◽  
Novel Strategy

Abstract This work is a continuation of our studies that showed that interleukin- 2 (IL-2)-activated murine bone marrow (ABM) cells have potent cytotoxic potential against murine cytomegalovirus (MCMV)-infected targets in vitro, without loss of reconstitutive ability in vivo. Our data show that ABM cells lyse the MCMV-infected cells in vitro, at both acute and chronic stages of infection; this lysis is specific for the MCMV- infected cells. ABM cells supplemented with IL-2 therapy virtually eradicated the viral infection and prolonged the survival of MCMV- infected Balb/c mice, whether or not they were immunocompromised by irradiation (P less than .001 in both situations). Efficacy of ABM cells alone or IL-2 alone was less than the combination of ABM cells and IL-2. The efficacy of combination treatment with ABM cells and IL-2 in improving the survival of MCMV-infected mice was comparable, whether used in a preventive or a therapeutic setting. Therapy with ABM plus IL- 2 also prevented the reactivation of chronic MCMV infection after irradiation. Preliminary findings indicate that Thy-1+ and asialo GM1+ cells limited the MCMV proliferation by approximately 30% and 80%, respectively, while BM macrophages limited the proliferation of MCMV by 100%. These results suggest that BM transplantation (BMT) with ABM cells followed by IL-2 therapy may constitute a novel strategy to improve the host resistance against cytomegalovirus infection after BMT.

Murine cytomegalovirus – Pseudomonas synergistic infections: comparison of virulent and attenuated virus

1987 ◽  
Vol 33 (10) ◽  
pp. 923-927 ◽  
Author(s):  
B. Kournikakis ◽  
L. A. Babiuk
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Salivary Glands ◽  
The Body ◽  
Murine Cytomegalovirus ◽  
Viral Neutralization ◽  
Lymphatic Circulation ◽  
Pulmonary Clearance ◽  
Attenuated Virus

The synergistic interactions between Pseudomonas aeruginosa and virulent or attenuated murine cytomegalovirus (MCMV) were compared in vivo. Virulent MCMV challenge at a dose of 5 × 105 pfu/mouse intraperitioneally, followed by intranasal superinfection with 5 × 106 cfu/mouse of Pseudomonas aeruginosa after 48 h resulted in greater than 80% mortality, apparently owing to a failure of pulmonary clearance mechanisms. Single infections, or the use of attenuated MCMV in synergistic infections, did not result in significant morbidity or mortality. Infection with virulent MCMV in vivo resulted in the rapid spread of virus to the lung, liver, and spleen, followed later by spread to the salivary glands. Attenuated virus was detected in salivary glands only. Virulent MCMV was more effective in adsorbing to, or infecting, spleen cells in vitro than attenuated virus. Viral neutralization experiments using anti-viral serum, rabbit complement, and anti-mouse IgG confirmed the presence of a nonneutralizing antibody on the surface of the virulent virus. Our results suggest that the presence of the nonneutralizing antibody on virulent MCMV allows the virus to preferentially infect, or adsorb to, Fc+ cells in the peritoneum. These cells may then carry the virus, via the lymphatic circulation, to other areas of the body, resulting in the replication of virus in multiple organs. Virus replication in the lung may, in part, be the cause of the observed suppression of pulmonary clearance.

scholarly journals Murine cytomegalovirus open reading frame m29.1 augments virus replication both in vitro and in vivo

2007 ◽  
Vol 88 (11) ◽  
pp. 2941-2951 ◽  
Author(s):  
Mohammad M. Ahasan ◽  
Clive Sweet
Keyword(s):  
Virus Replication ◽  
Post Infection ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Open Reading Frame ◽  
Murine Cytomegalovirus ◽  
Reading Frame ◽  
Codon Mutation

Murine cytomegalovirus mutant Rc29, with a premature stop codon mutation in the m29 open reading frame (ORF), produced no apparent phenotype in cell culture or following infection of BALB/c mice. In contrast, a similar mutant virus, Rc29.1, with a premature stop codon mutation in its m29.1 ORF, showed reduced virus yields (2–3 log10 p.f.u. ml−1) in tissue culture. Mutant virus yields in BALB/c mice were delayed, reduced (∼1 log10 p.f.u. per tissue) and persisted less well in salivary glands compared with wild-type (wt) and revertant (Rv29.1) virus. In severe combined immunodeficiency mice, Rc29.1 virus showed delayed and reduced replication initially in all tissues (liver, spleen, kidneys, heart, lung and salivary glands). This delayed death until 31 days post-infection (p.i.) compared with wt (23 days p.i.) but at death virus yields were similar to wt. m29 gene transcription was initiated at early times post-infection, while production of a transcript from ORF m29.1 in the presence of cycloheximide indicated that it was an immediate-early gene. ORFs m29.1 and M28 are expressed from a bicistronic message, which is spliced infrequently. However, it is likely that each ORF expresses its own protein, as antiserum derived in rabbits to the m29.1 protein expressed in bacteria from the m29.1 ORF detected only one protein in Western blot analysis of the size predicted for the m29.1 protein. Our results suggest that neither ORF is essential for virus replication but m29.1 is important for optimal viral growth in vitro and in vivo.

scholarly journals Dendritic Cell Responses to Early Murine Cytomegalovirus Infection

2003 ◽  
Vol 197 (7) ◽  
pp. 885-898 ◽  
Author(s):  
Marc Dalod ◽  
Tanya Hamilton ◽  
Rachelle Salomon ◽  
Thais P. Salazar-Mather ◽  
Stanley C. Henry ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
T Cell Activation ◽  
Cell Activation ◽  
Lymphocyte Activation ◽  
Murine Cytomegalovirus ◽  
Cell Responses ◽  
Dc Maturation

Differentiation of dendritic cells (DCs) into particular subsets may act to shape innate and adaptive immune responses, but little is known about how this occurs during infections. Plasmacytoid dendritic cells (PDCs) are major producers of interferon (IFN)-α/β in response to many viruses. Here, the functions of these and other splenic DC subsets are further analyzed after in vivo infection with murine cytomegalovirus (MCMV). Viral challenge induced PDC maturation, their production of high levels of innate cytokines, and their ability to activate natural killer (NK) cells. The conditions also licensed PDCs to efficiently activate CD8 T cells in vitro. Non-plasmacytoid DCs induced T lymphocyte activation in vitro. As MCMV preferentially infected CD8α+ DCs, however, restricted access to antigens may limit plasmacytoid and CD11b+ DC contribution to CD8 T cell activation. IFN-α/β regulated multiple DC responses, limiting viral replication in all DC and IL-12 production especially in the CD11b+ subset but promoting PDC accumulation and CD8α+ DC maturation. Thus, during defense against a viral infection, PDCs appear specialized for initiation of innate, and as a result of their production of IFN-α/β, regulate other DCs for induction of adaptive immunity. Therefore, they may orchestrate the DC subsets to shape endogenous immune responses to viruses.

scholarly journals MCMV Centrifugal Enhancement: A New Spin on an Old Topic

Pathogens ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1577
Author(s):  
Trevor J. Hancock ◽  
Morgan Lynn Hetzel ◽  
Andrea Ramirez ◽  
Tim E. Sparer
Keyword(s):  
Tissue Culture ◽  
Salivary Gland ◽  
Vaccine Development ◽  
Submicron Particles ◽  
Murine Cytomegalovirus ◽  
Submicron Particle ◽  
Congenital Infections ◽  
Life Threatening

Human cytomegalovirus (HCMV) is a ubiquitous pathogen infecting a majority of people worldwide, with diseases ranging from mild to life-threatening. Its clinical relevance in immunocompromised people and congenital infections have made treatment and vaccine development a top priority. Because of cytomegaloviruses’ species specificity, murine cytomegalovirus (MCMV) models have historically informed and advanced translational CMV therapies. Using the phenomenon of centrifugal enhancement, we explored differences between MCMVs derived in vitro and in vivo. We found centrifugal enhancement on tissue culture-derived virus (TCV) was ~3× greater compared with salivary gland derived virus (SGV). Using novel “flow virometry”, we found that TCV contained a distinct submicron particle composition compared to SGV. Using an inhibitor of exosome production, we show these submicron particles are not extracellular vesicles that contribute to centrifugal enhancement. We examined how these differences in submicron particles potentially contribute to differing centrifugal enhancement phenotypes, as well as broader in vivo vs. in vitro MCMV differences.

scholarly journals Adoptive transfer of anti-cytomegalovirus effect of interleukin-2- activated bone marrow: potential application in transplantation

Blood ◽  
1991 ◽  
Vol 78 (3) ◽  
pp. 720-727
Author(s):  
R Agah ◽  
BS Charak ◽  
V Chen ◽  
A Mazumder
Keyword(s):  
Bone Marrow ◽  
Interleukin 2 ◽  
Murine Cytomegalovirus ◽  
Mcmv Infection ◽  
Murine Bone Marrow ◽  
Therapeutic Setting ◽  
Infected Cells ◽  
Novel Strategy

This work is a continuation of our studies that showed that interleukin- 2 (IL-2)-activated murine bone marrow (ABM) cells have potent cytotoxic potential against murine cytomegalovirus (MCMV)-infected targets in vitro, without loss of reconstitutive ability in vivo. Our data show that ABM cells lyse the MCMV-infected cells in vitro, at both acute and chronic stages of infection; this lysis is specific for the MCMV- infected cells. ABM cells supplemented with IL-2 therapy virtually eradicated the viral infection and prolonged the survival of MCMV- infected Balb/c mice, whether or not they were immunocompromised by irradiation (P less than .001 in both situations). Efficacy of ABM cells alone or IL-2 alone was less than the combination of ABM cells and IL-2. The efficacy of combination treatment with ABM cells and IL-2 in improving the survival of MCMV-infected mice was comparable, whether used in a preventive or a therapeutic setting. Therapy with ABM plus IL- 2 also prevented the reactivation of chronic MCMV infection after irradiation. Preliminary findings indicate that Thy-1+ and asialo GM1+ cells limited the MCMV proliferation by approximately 30% and 80%, respectively, while BM macrophages limited the proliferation of MCMV by 100%. These results suggest that BM transplantation (BMT) with ABM cells followed by IL-2 therapy may constitute a novel strategy to improve the host resistance against cytomegalovirus infection after BMT.

scholarly journals Patterns of Autologous and Nonautologous Interactions between Core Nuclear Egress Complex (NEC) Proteins of α-, β- and γ-Herpesviruses

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 303 ◽  
Author(s):  
Sigrun Häge ◽  
Eric Sonntag ◽  
Eva Maria Borst ◽  
Pierre Tannig ◽  
Lisa Seyler ◽  
...  
Keyword(s):  
Confocal Imaging ◽  
Murine Cytomegalovirus ◽  
Varicella Zoster ◽  
Barr Virus ◽  
Functional Complementarity ◽  
Nuclear Egress ◽  
Murine Fibroblasts ◽  
Epstein Barr

Nuclear egress is a regulated process shared by α-, β- and γ-herpesviruses. The core nuclear egress complex (NEC) is composed of the membrane-anchored protein homologs of human cytomegalovirus (HCMV) pUL50, murine cytomegalovirus (MCMV) pM50, Epstein–Barr virus (EBV) BFRF1 or varicella zoster virus (VZV) Orf24, which interact with the autologous NEC partners pUL53, pM53, BFLF2 or Orf27, respectively. Their recruitment of additional proteins leads to the assembly of a multicomponent NEC, coordinately regulating viral nucleocytoplasmic capsid egress. Here, the functionality of VZV, HCMV, MCMV and EBV core NECs was investigated by coimmunoprecipitation and confocal imaging analyses. Furthermore, a recombinant MCMV, harboring a replacement of ORF M50 by UL50, was analyzed both in vitro and in vivo. In essence, core NEC interactions were strictly limited to autologous NEC pairs and only included one measurable nonautologous interaction between the homologs of HCMV and MCMV. A comparative analysis of MCMV-WT versus MCMV-UL50-infected murine fibroblasts revealed almost identical phenotypes on the levels of protein and genomic replication kinetics. In infected BALB/c mice, virus spread to lung and other organs was found comparable between these viruses, thus stating functional complementarity. In conclusion, our study underlines that herpesviral core NEC proteins are functionally conserved regarding complementarity of core NEC interactions, which were found either virus-specific or restricted within subfamilies.

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