Systems biology of natural simian immunodeficiency virus infections.

PURPOSE OF REVIEW A key factor driving AIDS-associated immunopathogenesis is chronic immune activation. Simian immunodeficiency virus (SIV) infection of African natural host species leads to high viremia, but low immune activation and absence of disease. Considerable progress in our understanding of pathological immune activation has come from comparative studies of SIV infection in pathogenic Asian macaque species and natural hosts. The focus of this review is to highlight recent work on the natural host model using high-throughput genomics. RECENT FINDINGS Several groups have independently conducted microarray gene expression profiling comparing in-vivo SIV infection in natural and non-natural hosts. A consistent finding between these studies is that both pathogenic SIV infection of macaques and nonpathogenic infections of natural hosts have strong induction of interferon-stimulated genes (ISGs) early on, but a key difference was that natural hosts down-modulated the interferon response rapidly after acute infection. The development of new genome-based resources for further study of the natural host model is discussed. SUMMARY Initial efforts using high-throughput biology to study SIV infection of natural hosts have effectively identified the ability of natural hosts to resolve interferon responses and immune activation. Further application of 'omic-based technologies coupled with integrative systems-based analysis should continue to yield progress.

[1]  Alan S. Perelson,et al.  Decay characteristics of HIV-1-infected compartments during combination therapy , 1997, Nature.

[2]  D. Douek,et al.  Differential Th17 CD4 T-cell depletion in pathogenic and nonpathogenic lentiviral infections. , 2008, Blood.

[3]  A. Haase,et al.  Early Resolution of Acute Immune Activation and Induction of PD-1 in SIV-Infected Sooty Mangabeys Distinguishes Nonpathogenic from Pathogenic Infection in Rhesus Macaques12 , 2008, The Journal of Immunology.

[4]  J. Carlis,et al.  Global genomic analysis reveals rapid control of a robust innate response in SIV-infected sooty mangabeys. , 2009, The Journal of clinical investigation.

[5]  M. Altfeld,et al.  DCs and NK cells: critical effectors in the immune response to HIV-1 , 2011, Nature Reviews Immunology.

[6]  T. Golub,et al.  DNA microarrays in clinical oncology. , 2002, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[7]  Eva K. Lee,et al.  Systems biology approach predicts immunogenicity of the yellow fever vaccine in humans , 2009, Nature Immunology.

[8]  Vasudha Sundaravaradan,et al.  SIV infection in natural hosts: resolution of immune activation during the acute-to-chronic transition phase. , 2011, Microbes and infection.

[9]  B. Beutler,et al.  TYPE I INTERFERONS (/) IN IMMUNITY AND AUTOIMMUNITY , 2005 .

[10]  P. Sharp,et al.  Human immunodeficiency viruses: SIV infection in wild gorillas , 2006, Nature.

[11]  L. Wain,et al.  Chimpanzee Reservoirs of Pandemic and Nonpandemic HIV-1 , 2006, Science.

[12]  J. Mesirov,et al.  Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. , 1999, Science.

[13]  J. Downing,et al.  Classification, subtype discovery, and prediction of outcome in pediatric acute lymphoblastic leukemia by gene expression profiling. , 2002, Cancer cell.

[14]  Ronald S Veazey,et al.  Paucity of CD4 (cid:1) CCR5 (cid:1) T cells is a typical feature of natural SIV hosts , 2022 .

[15]  H. Schuitemaker,et al.  Low Immune Activation despite High Levels of Pathogenic Human Immunodeficiency Virus Type 1 Results in Long-Term Asymptomatic Disease , 2007, Journal of Virology.

[16]  Kathleen A. Kennedy,et al.  Systems biology approaches identify ATF3 as a negative regulator of Toll-like receptor 4 , 2006, Nature.

[17]  A. Perelson,et al.  Acute Loss of Intestinal CD4+ T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence1 , 2007, The Journal of Immunology.

[18]  B. Hahn,et al.  A Novel CCR5 Mutation Common in Sooty Mangabeys Reveals SIVsmm Infection of CCR5-Null Natural Hosts and Efficient Alternative Coreceptor Use In Vivo , 2010, PLoS pathogens.

[19]  Shuzhao Li,et al.  Systems vaccinology: Probing humanity’s diverse immune systems with vaccines , 2014, Proceedings of the National Academy of Sciences.

[20]  D. Douek,et al.  Nonprogressive and progressive primate immunodeficiency lentivirus infections. , 2010, Immunity.

[21]  F. Kirchhoff,et al.  Is Nef the elusive cause of HIV-associated hematopoietic dysfunction? , 2008, The Journal of clinical investigation.

[22]  G. Silvestri,et al.  Early Divergence in Lymphoid Tissue Apoptosis between Pathogenic and Nonpathogenic Simian Immunodeficiency Virus Infections of Nonhuman Primates , 2007, Journal of Virology.

[23]  F. Barré-Sinoussi,et al.  Plasmacytoid Dendritic Cell Dynamics and Alpha Interferon Production during Simian Immunodeficiency Virus Infection with a Nonpathogenic Outcome , 2008, Journal of Virology.

[24]  A. Aderem,et al.  A 2020 vision for vaccines against HIV, tuberculosis and malaria , 2011, Nature.

[25]  F. Barré-Sinoussi,et al.  African non human primates infected by SIV - why don't they get sick? Lessons from studies on the early phase of non-pathogenic SIV infection. , 2009, Current HIV research.

[26]  Nir Hacohen,et al.  Systems biology approaches to dissect mammalian innate immunity. , 2011, Current opinion in immunology.

[27]  P. Bieniasz,et al.  Human immunodeficiency virus, restriction factors, and interferon. , 2009, Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research.

[28]  F. Barré-Sinoussi,et al.  Nonpathogenic SIV infection of African green monkeys induces a strong but rapidly controlled type I IFN response. , 2009, The Journal of clinical investigation.

[29]  J. Brenchley,et al.  Immunodeficiency lentiviral infections in natural and non-natural hosts. , 2011, Blood.

[30]  Mario Roederer,et al.  Emerging concepts in the immunopathogenesis of AIDS. , 2009, Annual review of medicine.

[31]  Judith N. Mandl,et al.  Divergent TLR7 and TLR9 signaling and type I interferon production distinguish pathogenic and nonpathogenic AIDS virus infections , 2008, Nature Medicine.

[32]  N. Hacohen,et al.  A Physical and Regulatory Map of Host-Influenza Interactions Reveals Pathways in H1N1 Infection , 2009, Cell.

[33]  J. Shendure.  The beginning of the end for microarrays? , 2008, Nature Methods.

[34]  Guido Silvestri,et al.  Understanding the benign nature of SIV infection in natural hosts. , 2007, The Journal of clinical investigation.

[35]  D. Douek,et al.  Toward an AIDS vaccine: lessons from natural simian immunodeficiency virus infections of African nonhuman primate hosts , 2009, Nature Medicine.

[36]  M. Katze,et al.  A Systems Biology Approach to Infectious Disease Research: Innovating the Pathogen-Host Research Paradigm , 2011, mBio.

[37]  M. Ostrowski,et al.  Distinct Transcriptional Profiles in Ex Vivo CD4+ and CD8+ T Cells Are Established Early in Human Immunodeficiency Virus Type 1 Infection and Are Characterized by a Chronic Interferon Response as Well as Extensive Transcriptional Changes in CD8+ T Cells , 2007, Journal of Virology.

[38]  Carole R. Baskin,et al.  Transcriptional Profiling in Pathogenic and Non-Pathogenic SIV Infections Reveals Significant Distinctions in Kinetics and Tissue Compartmentalization , 2009, PLoS pathogens.

[39]  M. Gerstein,et al.  RNA-Seq: a revolutionary tool for transcriptomics , 2009, Nature Reviews Genetics.

[40]  William J. Kaiser,et al.  Divergent Host Responses during Primary Simian Immunodeficiency Virus SIVsm Infection of Natural Sooty Mangabey and Nonnatural Rhesus Macaque Hosts , 2005, Journal of Virology.

[41]  Bali Pulendran,et al.  Learning immunology from the yellow fever vaccine: innate immunity to systems vaccinology , 2009, Nature Reviews Immunology.

[42]  Tanya M. Teslovich,et al.  Chronic CD4+ T-Cell Activation and Depletion in Human Immunodeficiency Virus Type 1 Infection: Type I Interferon-Mediated Disruption of T-Cell Dynamics , 2007, Journal of Virology.

[43]  J. Brenchley,et al.  Down-regulation of CD4 by memory CD4+ T cells in vivo renders African green monkeys resistant to progressive SIVagm infection , 2009, Nature Medicine.

[44]  Bastian R. Angermann,et al.  Yellow fever vaccine induces integrated multilineage and polyfunctional immune responses , 2008, The Journal of experimental medicine.

[45]  Carole R. Baskin,et al.  Critical Loss of the Balance between Th17 and T Regulatory Cell Populations in Pathogenic SIV Infection , 2009, PLoS pathogens.

[46]  F. Barré-Sinoussi,et al.  Antiinflammatory profiles during primary SIV infection in African green monkeys are associated with protection against AIDS. , 2005, The Journal of clinical investigation.

[47]  A. Perelson,et al.  Short-Lived Infected Cells Support Virus Replication in Sooty Mangabeys Naturally Infected with Simian Immunodeficiency Virus: Implications for AIDS Pathogenesis , 2008, Journal of Virology.

[48]  Zachary D. Smith,et al.  Unbiased Reconstruction of a Mammalian Transcriptional Network Mediating Pathogen Responses , 2009 .

[49]  D. Zak,et al.  Systems biology of innate immunity , 2009, Immunological reviews.

[50]  G. Silvestri,et al.  Generalized immune activation and innate immune responses in simian immunodeficiency virus infection. , 2011, Current opinion in HIV and AIDS.

[51]  B. Beutler,et al.  Type I interferons (alpha/beta) in immunity and autoimmunity. , 2005, Annual review of immunology.

[52]  J. Herbeuval,et al.  HIV-1 immunopathogenesis: how good interferon turns bad. , 2007, Clinical immunology.

[53]  R. Koup,et al.  Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia. , 2003, Immunity.

[54]  Philip R. Johnson,et al.  An African primate lentivirus (SIVsmclosely related to HIV-2 , 1989, Nature.

[55]  S. Staprans,et al.  Timely triggering of homeostatic mechanisms involved in the regulation of T-cell levels in SIVsm-infected sooty mangabeys. , 2005, Blood.

[56]  Shawn O'Neil,et al.  Differential CD4+ T-Lymphocyte Apoptosis and Bystander T-Cell Activation in Rhesus Macaques and Sooty Mangabeys during Acute Simian Immunodeficiency Virus Infection , 2008, Journal of Virology.

[57]  Eva K. Lee,et al.  Systems Biology of Seasonal Influenza Vaccination in Humans , 2011, Nature Immunology.

[58]  L. Trautmann,et al.  Solving vaccine mysteries: a systems biology perspective , 2011, Nature Immunology.

[59]  F. Barré-Sinoussi,et al.  Programmed cell death and AIDS: significance of T-cell apoptosis in pathogenic and nonpathogenic primate lentiviral infections. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[60]  A. Perelson,et al.  Simian Immunodeficiency Virus SIVagm Dynamics in African Green Monkeys , 2008, Journal of Virology.

[61]  F. Kirchhoff,et al.  Inefficient Nef-Mediated Downmodulation of CD3 and MHC-I Correlates with Loss of CD4+ T Cells in Natural SIV Infection , 2008, PLoS pathogens.

[62]  J. Lifson,et al.  Downregulation of Robust Acute Type I Interferon Responses Distinguishes Nonpathogenic Simian Immunodeficiency Virus (SIV) Infection of Natural Hosts from Pathogenic SIV Infection of Rhesus Macaques , 2010, Journal of Virology.

[63]  S. Staprans,et al.  Severe Depletion of Mucosal CD4+ T Cells in AIDS-Free Simian Immunodeficiency Virus-Infected Sooty Mangabeys1 , 2007, The Journal of Immunology.

[64]  P. D. de Bakker,et al.  Comparative transcriptomics of extreme phenotypes of human HIV-1 infection and SIV infection in sooty mangabey and rhesus macaque. , 2011, The Journal of clinical investigation.

[65]  Z. Grossman,et al.  Progressive CD4+ central–memory T cell decline results in CD4+ effector–memory insufficiency and overt disease in chronic SIV infection , 2007, The Journal of experimental medicine.