Jakob Ettinger

Publications of Jakob Ettinger

• Deletion of the rat cytomegalovirus immediate early 1 gene results in a virus capable of establishing latency but with lower levels of acute virus replication and latency that compromise reactivation efficiency.

  Authors: Gordon R. Sandford, Uwe Schumacher, Jakob Ettinger, Wolfram Brune, Gary S Hayward, William H Burns, Sebastian Voigt

  The Journal of general virology. 11/2009;

  The IE1 and IE2 proteins encoded by the major immediate-early (MIE) transcription unit of cytomegaloviruses are thought to play key roles in the switch between latent and lytic cycle infection.The IE1 and IE2 proteins encoded by the major immediate-early (MIE) transcription unit of cytomegaloviruses are thought to play key roles in the switch between latent and lytic cycle infection. Whilst IE2 is essential for triggering the lytic cycle, the exact roles of IE1 have not been resolved. An MIE-exon 4 deleted rat cytomegalovirus (DeltaIE1) failed to synthesize the IE1 protein and did not disperse promyelocytic leukemia bodies (PML) early post-infection, but it was still capable of normal replication in fibroblast cell culture. However, DeltaIE1 had diminished ability to infect salivary glands persistently in vivo and to reactivate from spleen explant cultures ex vivo. Quantitation of viral genomes in spleens of infected animals revealed a reduced amount of DeltaIE1 virus produced during acute infection, suggesting a role for IE1 as a regulator in establishing a chronic or persistent infection, rather than in more directly influencing the latency or reactivation processes.

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• Cytomegalovirus evasion of innate immunity by subversion of the NKR-P1B:Clr-b missing-self axis.

  Authors: Sebastian Voigt, Aruz Mesci, Jakob Ettinger, Jason H Fine, Peter Chen, Wayne Chou, James R Carlyle

  Immunity. 06/2007; 26(5):617-27.

  Cytomegaloviruses are known to encode several gene products that function to subvert MHC-dependent immune recognition. Here we characterize a rat cytomegalovirus (RCMV) C-type lectin-like (RCTL) geneCytomegaloviruses are known to encode several gene products that function to subvert MHC-dependent immune recognition. Here we characterize a rat cytomegalovirus (RCMV) C-type lectin-like (RCTL) gene product with homology to the Clr ligands for the NKR-P1 receptors. RCMV infection rapidly extinguished host Clr-b expression, thereby sensitizing infected cells to killing by natural killer (NK) cells. However, the RCTL protein functioned as a decoy ligand to protect infected cells from NK killing via direct interaction with the NKR-P1B inhibitory receptor. In vivo, an RCTL mutant virus displayed diminished virulence in an NK-dependent and strain-specific manner, suggesting that host NKR-P1 polymorphisms have evolved to avert the viral decoy mechanism while maintaining Clr-b recognition to preserve self tolerance. These findings reveal a unique strategy adopted by cytomegaloviruses to evade MHC-independent self-nonself discrimination. The existence of lectin-like genes in several poxviruses suggests that this may represent a common theme for viral evasion of innate immunity.