scholarly journals Immunization with a murine cytomegalovirus based vector encoding retrovirus envelope confers strong protection from Friend retrovirus challenge infection

2019 ◽  
Vol 15 (9) ◽  
pp. e1008043
Author(s):  
Nadine Bongard ◽  
Vu Thuy Khanh Le-Trilling ◽  
Anna Malyshkina ◽  
Meike Rückborn ◽  
Kerstin Wohlgemuth ◽  
...  
Keyword(s):  
Challenge Infection ◽  
Murine Cytomegalovirus ◽  
Friend Retrovirus

scholarly journals Expanded Regulatory T Cells in Chronically Friend Retrovirus-Infected Mice Suppress Immunity to a Murine Cytomegalovirus Superinfection

2014 ◽  
Vol 88 (23) ◽  
pp. 13892-13896 ◽  
Author(s):  
J. Duppach ◽  
S. Francois ◽  
J. J. Joedicke ◽  
U. Dittmer ◽  
A. R. M. Kraft
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Murine Cytomegalovirus ◽  
Friend Retrovirus

scholarly journals Localization of Viral Epitope-Specific CD8 T Cells during Cytomegalovirus Latency in the Lungs and Recruitment to Lung Parenchyma by Airway Challenge Infection

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 918
Author(s):  
Franziska Blaum ◽  
Dominika Lukas ◽  
Matthias J. Reddehase ◽  
Niels A. W. Lemmermann
Keyword(s):  
T Cells ◽  
Cd8 T Cells ◽  
Hematopoietic Cell Transplantation ◽  
Alveolar Epithelium ◽  
Challenge Infection ◽  
Murine Cytomegalovirus ◽  
Effector Memory ◽  
Memory Cells ◽  
Viral Epitope ◽  
Effector Memory Cells

Interstitial pneumonia is a life-threatening clinical manifestation of cytomegalovirus infection in recipients of hematopoietic cell transplantation (HCT). The mouse model of experimental HCT and infection with murine cytomegalovirus revealed that reconstitution of virus-specific CD8+ T cells is critical for resolving productive lung infection. CD8+ T-cell infiltrates persisted in the lungs after the establishment of latent infection. A subset defined by the phenotype KLRG1+CD62L− expanded over time, a phenomenon known as memory inflation (MI). Here we studied the localization of these inflationary T effector-memory cells (iTEM) by comparing their frequencies in the intravascular and transmigration compartments, the IVC and TMC, respectively, with their frequency in the extravascular compartment (EVC), the alveolar epithelium. Frequencies of viral epitope-specific iTEM were comparable in the IVC and TMC but were reduced in the EVC, corresponding to an increase in KLRG1−CD62L− conventional T effector-memory cells (cTEM) and a decrease in functional IFNγ+CD8+ T cells. As maintained expression of KLRG1 requires stimulation by antigen, we conclude that iTEM lose KLRG1 and convert to cTEM after transmigration into the EVC because pneumocytes are not latently infected and, therefore, do not express antigens. Accordingly, antigen re-expression upon airway challenge infection recruited virus-specific CD8+ T cells to TMC and EVC.

scholarly journals Immunodominant Cytomegalovirus Epitopes Suppress Subdominant Epitopes in the Generation of High-Avidity CD8 T Cells

Pathogens ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 956
Author(s):  
Kirsten Freitag ◽  
Sara Hamdan ◽  
Matthias J. Reddehase ◽  
Rafaela Holtappels
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Immune Escape ◽  
Cd8 T Cell ◽  
Antigenic Drift ◽  
Murine Cytomegalovirus ◽  
High Avidity ◽  
Infected Cells ◽  
Cd8 T Cell Memory

CD8+ T-cell responses to pathogens are directed against infected cells that present pathogen-encoded peptides on MHC class-I molecules. Although natural responses are polyclonal, the spectrum of peptides that qualify for epitopes is remarkably small even for pathogens with high coding capacity. Among those few that are successful at all, a hierarchy exists in the magnitude of the response that they elicit in terms of numbers of CD8+ T cells generated. This led to a classification into immunodominant and non-immunodominant or subordinate epitopes, IDEs and non-IDEs, respectively. IDEs are favored in the design of vaccines and are chosen for CD8+ T-cell immunotherapy. Using murine cytomegalovirus as a model, we provide evidence to conclude that epitope hierarchy reflects competition on the level of antigen recognition. Notably, high-avidity cells specific for non-IDEs were found to expand only when IDEs were deleted. This may be a host’s back-up strategy to avoid viral immune escape through antigenic drift caused by IDE mutations. Importantly, our results are relevant for the design of vaccines based on cytomegaloviruses as vectors to generate high-avidity CD8+ T-cell memory specific for unrelated pathogens or tumors. We propose the deletion of vector-encoded IDEs to avoid the suppression of epitopes of the vaccine target.

scholarly journals The m15 Locus of Murine Cytomegalovirus Modulates Natural Killer Cell Responses to Promote Dissemination to the Salivary Glands and Viral Shedding

Pathogens ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 866
Author(s):  
Baca Chan ◽  
Maja Arapović ◽  
Laura Masters ◽  
Francois Rwandamuiye ◽  
Stipan Jonjić ◽  
...  
Keyword(s):  
Nk Cells ◽  
Salivary Glands ◽  
Natural Killer ◽  
Nk Cell ◽  
Acute Infection ◽  
Killer Cell ◽  
Viral Escape ◽  
Murine Cytomegalovirus ◽  
Viral Shedding ◽  
Cell Responses

As the largest herpesviruses, the 230 kb genomes of cytomegaloviruses (CMVs) have increased our understanding of host immunity and viral escape mechanisms, although many of the annotated genes remain as yet uncharacterised. Here we identify the m15 locus of murine CMV (MCMV) as a viral modulator of natural killer (NK) cell immunity. We show that, rather than discrete transcripts from the m14, m15 and m16 genes as annotated, there are five 3′-coterminal transcripts expressed over this region, all utilising a consensus polyA tail at the end of the m16 gene. Functional inactivation of any one of these genes had no measurable impact on viral replication. However, disruption of all five transcripts led to significantly attenuated dissemination to, and replication in, the salivary glands of multiple strains of mice, but normal growth during acute infection. Disruption of the m15 locus was associated with heightened NK cell responses, including enhanced proliferation and IFNγ production. Depletion of NK cells, but not T cells, rescued salivary gland replication and viral shedding. These data demonstrate the identification of multiple transcripts expressed by a single locus which modulate, perhaps in a concerted fashion, the function of anti-viral NK cells.

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