MODULATION OF INNATE IMMUNE RESPONSES BY CYTOMEGALOVIRUS

$76,080P51FY2010RRNIH

Oregon Health & Science University, Portland OR

Investigators

Linked publications, trials & patents

Paper 39531811 Paper 37708918 Paper 37499736 Paper 36939178 Paper 36917864 Paper 36907435 Paper 35316218 Paper 34915175 Paper 34540718 Paper 34218053 Paper 33524104 Paper 32637610 Paper 30522845 Paper 30201462 Paper 30139430 Paper 30082858 Paper 29971796 Paper 29520866 Paper 29407362 Paper 29063622 Paper 28936565 Paper 28873045 Paper 28284896 Paper 28154169 Paper 27859771 Paper 27635049 Paper 27357159 Paper 27265023 Paper 27045379 Paper 26957355 Paper 26721679 Paper 26621857 Paper 26472457 Paper 26406934 Paper 26284599 Paper 26223349 Paper 26187412 Paper 26070857 Paper 26069734 Paper 25976012 Paper 25913366 Paper 25612682 Paper 25545382 Paper 25470211 Paper 25376878 Paper 25332397 Paper 25219362 Paper 25209798 Paper 25034695 Paper 25011649 Paper 24959820 Paper 24862904 Paper 24709587 Paper 24681059 Paper 24639226 Paper 24560476 Paper 24448900 Paper 24413616 Paper 24408325 Paper 24390280 Paper 24375078 Paper 24329418 Paper 24324408 Paper 24215535 Paper 24210020 Paper 24202052 Paper 24200973 Paper 24179112 Paper 24174435 Paper 24092271 Paper 24080959 Paper 24077067 Paper 24063855 Paper 24055980 Paper 23959334 Paper 23948905 Paper 23921100 Paper 23908248 Paper 23891857 Paper 23881606 Paper 23816568 Paper 23709130 Paper 23675327 Paper 23651991 Paper 23594602 Paper 23568382 Paper 23559626 Paper 23550738 Paper 23543038 Paper 23482462 Paper 23463525 Paper 23442156 Patent 9434921 Patent 9314506 Patent 9249427 Patent 7972849 Patent 7695917 Patent 6558911 Patent 4602005 Patent 4602003

Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The ultimate inability of the immune system to eliminate cytomegalovirus (CMV) from the host is likely due to sophisticated viral evasion mechanisms that target many aspects of the host immune system. In this project, we will try to gain a better understanding of the molecular mechanisms by which CMV modulates the induction of innate immune responses, particularly the interferon response. Specific aim 1 is to identify how HCMV activates interferon-regulatory factor 3 (IRF3). This aim has been completed and the results have been published. Specific Aims 2 and 3: are to determine how human and rhesus CMV interfere with IRF3-dependent transcriptional induction of interferon-stimulated genes (ISGs). We have tested our original hypothesis that the tegument proteins pp65 and pp71 are responsible for inhibiting IRF3 activation by RhCMV by generating deletion viruses. However, since these viruses still inhibit IRF3 activation, we now hypothesize that RhCMV contains additional IRF3 inhibitory genes. Current experiments are aimed at identifying these genes. In addition, we now explore the inhibition of IFN-dependent ISG induction by RhCMV and we have generated evidence that HCMV also inhibits IRF3 activation. In a competitive supplement to this application, we will examine whether RhCMV lacking pp65 and pp71 is capable of primary and re-infection in rhesus macaques. This is a new grant, but represents a competitive supplement to parent grant (RO1 AI070890) to study the role of RhCMV pp65 in vivo.

View original record on NIH RePORTER →