Johannes Schweininger

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A3 Structural biology of plant potyvirus and cytomegalovirus effector proteins

Principal investigator
Yves Muller

Mentor
Thomas Stamminger

Structural investigation of the interaction between CMV IE1 and host proteins

The human cytomegalovirus, HCMV, is a dsDNA virus of the β-herpesvirus subfamily. Infections can lead to severe complications for immunocompromised patients like transplant recipients, AIDS patients or newborns, while in immunocompetent individuals, latent or persistent infections are mostly asymptomatic. During CMV infection, the virus replicates inside the nucleus. Initially, the viral gene expression is antagonized by the innate immune mechanism mediated by subnuclear protein complexes termed nuclear domain 10 (ND10). These complexes consist of various proteins, mainly Daxx, SP100 and PML, with the latter acting as a critical key component for ND10 formation and structure. One way of CMVs to evade the host’s immune system is the introduction of the immediate early 1 protein (IE1). Upon expression, IE1 targets PML. This leads to the loss of SUMOylated PML and SP100 and causes the dispersal of the ND10, which abrogates its antiviral effects. The exact mechanism of the IE1 mediated ND10 disruption is still unclear. There is a crystal structure of rhesus macaque CMV IE1, but neither of PML nor a complex of IE1 and PML. This part of the project aims to get further insights into the molecular interactions between both proteins.

Figure: Targeting and subsequent disruption of nuclear ND10 by CMV IE1.
Adapted from: Tavalai N and Stamminger T, 2011. Intrinsic cellular defense mechanisms targeting human cytomegalovirus. Virus Research 157, 128-133.

 

Publications

 

 

 

Presentations

October 2016 8th Annual Retreat, Erlangen School of Molecular Communication, Schloss Schney, Lichtenfels, Germany
”Towards the structural characterization of HCMV IE1 and human PML”
Poster
     
July 2015 7th Annual Retreat, Erlangen School of Molecular Communication, Schloss Hirschberg, Beilngries, Germany
”Purification of the HCMV IE1 - PML complex for structure determination”
Talk
     
July 2014 6th Annual Retreat, Erlangen School of Molecular Communication, Kloster Banz, Bad Staffelstein, Germany
”Towards the structural characterization of the interaction between cytomegalovirus IE1 and host PML”
Poster
     
June 2014 Rabensteiner Kolleg, Pottenstein, Germany
”Towards the structural characterization of the interaction between cytomegalovirus IE1 and host PML”
Talk