Dynamics of innate immunity are key to chronic immune activation in AIDSBenecke, Arndta,b; Gale, Michael Jr.c; Katze, Michael G.dCurrent Opinion in HIV and AIDS: January 2012 - Volume 7 - Issue 1 - p 79–85 doi: 10.1097/COH.0b013e32834dde31 SYSTEMS BIOLOGY IN UNDERSTANDING HIV PATHOGENESIS AND GUIDING VACCINE DEVELOPMENT: Edited by Rafick-Pierre Sékaly and Bali Pulendran Abstract Author Information Purpose of review We propose here that the dynamics rather than the structure of cellular and viral networks play a determining role in chronic immune activation of HIV-infected individuals. A number of novel avenues of experimental analysis and modeling strategies are discussed to conclusively address these network dynamics in the future. Recent findings Recent insights into the molecular dynamics of immune activation and its control following simian immunodeficiency virus (SIV) infection in natural host primates has provided possible alternate interpretations of SIV and HIV pathogenesis. Concomitant with insights gained in other host–pathogen systems, as well as an increased understanding of innate immune activation mechanisms, these observations lead to a new model for the timing of innate HIV immune responses and a possible primordial role of this timing in programming chronic immune activation. Summary Chronic immune activation is today considered the leading cause of AIDS in HIV-infected individuals. Systems biology has recently lent arguments for considering chronic immune activation a result of untimely innate immune responses by the host to the infection. Future strategies for the analysis, comprehension, and incorporation of the dynamic component of immune activation into HIV vaccination strategies are discussed. aInstitut des Hautes Études Scientifiques, Bures sur Yvette bVaccine Research Institute, INSERM U955, Institut Mondor de Recherche Biomédicale, Créteil, France cDepartment of Immunology dDepartment of Microbiology, University of Washington, Seattle, Washington, USA Correspondence to Michael G. Katze, Professor of Microbiology, Box 358070, University of Washington, Seattle, WA 98195, USA. Tel: +1 206 732 6135; e-mail: firstname.lastname@example.org,http://viromics.washington.edu © 2012 Lippincott Williams & Wilkins, Inc.