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Principal Investigator: CHRISTOPHER P. HILL
Organization: UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH
Fiscal Year: 2019
Award: $245,589
Funding agency: National Institute of Allergy and Infectious Diseases
ABSTRACT
The success of antiretroviral therapy (ART) has transformed the HIV/AIDS pandemic into a life-long chronic
disease, yet major challenges remain as a growing population of ~35 million patients living with HIV continues
to face significant health challenges. These include side-effects and toxicity of ART, immune dysfunction and
chronic inflammation that results in diseases associated with accelerated aging, and an increase in non-AIDS
defining cancers. Continued infections also heighten the risk of multidrug resistance. Thus, the search for a
sterilizing or functional cure that permits years of drug-free life for infected individuals has moved to center
stage for HIV/AIDS research.. We now propose to contribute to the basic science that underlies these issues
by: 1) Use hu-mice to determine the pathway of viral reactivation from latency at the anatomical and cellular
levels, 2) Determine molecular mechanisms that are important for the establishment, maintenance, and
reversal of latency, and 3) Decipher molecular mechanisms that mediate immune responses, with a focus on
receptors that localize antibodies, regulate innate immunity, and localize or regulate T-cells. These studies will
advance understanding of the latent reservoir, HIV gene expression, immune responses, and will inform the
development of eradication strategies.
Terms: <AIDS Virus><AIDS/HIV><AIDS/HIV problem><ATGN><Abscission><Acquired Immune Deficiency Syndrome Virus><Acquired Immunodeficiency Syndrome Virus><Active Immunization><Aging><Anatomic><Anatomic Sites><Anatomic Structure, System, or Substance><Anatomic Structures and Systems><Anatomic structures><Anatomical Sciences><Anatomy><Anatomy Qualifier><Antibodies><Antibody Therapy><Antigens><Basic Research><Basic Science><Binding><Biochemical><Body Tissues><Cancer Treatment><Cancers><Cell Body><Cells><Cellular biology><Chronic><Chronic Disease><Chronic Illness><Complex><Coupled><DNA Polymerase II><DNA Polymerase epsilon><DNA-Dependent DNA Polymerase II><Data><Development><Disease><Disorder><Drugs><Elements><Excision><Extirpation><Face><Future><Gene Expression><Gene Transcription><General Viruses><Genetic Transcription><HIV><HIV vaccine><HIV/AIDS><HIV/AIDS Vaccines><HIV/AIDS problem><Health><Homing><Human><Human Immunodeficiency Viruses><IMiD><IVIS SpectrumCT><IVIS imaging><IVIS optical imaging><IVIS spectral imaging><IVIS spectrum><IVIS system><Immune><Immune Diseases><Immune Disorders><Immune Dysfunction><Immune System Diseases><Immune System Disorder><Immune System Dysfunction><Immune System and Related Disorders><Immune response><Immunes><Immunodeficiency and Immunosuppression Disorders><Immunologic Diseases><Immunologic Receptors><Immunological Diseases><Immunological Dysfunction><Immunological Receptors><Immunological System Dysfunction><Immunological response><Immunology><Immunomodulators><Individual><Infection><Infection prevention><Inflammation><Innate Immunity><LAV-HTLV-III><LPAM-1 adhesion molecule><Latent virus infection phase><Letters><Life><Location><Lymphadenopathy-Associated Virus><Maintenance><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Mediating><Medication><Mice><Mice Mammals><Modern Man><Molecular><Molecular Interaction><Monitor><Moths><Mucins><Mucosa><Mucosal Tissue><Mucous Membrane><Mucus Glycoprotein><Multi-Drug Resistance><Multidrug Resistance><Multiple Drug Resistance><Multiple Drug Resistant><Murine><Mus><Native Immunity><Natural Immunity><Non-Polyadenylated RNA><Non-Specific Immunity><Nonspecific Immunity><P-TEFb><PD-1 checkpoint pathway><PD-1 pathway><PD-1 signaling pathway><PD1 checkpoint pathway><PD1 pathway><PD1 signaling pathway><Passive Immunization><Pathway interactions><Patients><Pharmaceutic Preparations><Pharmaceutical Preparations><Pol II><Population><Positive Transcription Elongation Factor B><Positive Transcriptional Elongation Factor B><Prevent infection><Proteins><RNA><RNA Expression><RNA Gene Products><Receptor Protein><Removal><Research><Resistance to Multi-drug><Resistance to Multidrug><Resistance to Multiple Drug><Resistant to Multiple Drug><Resistant to multi-drug><Resistant to multidrug><Ribonucleic Acid><Risk><Role><Route><Structure><Surface><Surgical Removal><T-Cells><T-Lymphocyte><Testing><Therapeutic><Therapeutic Agents><Tissues><Toxic effect><Toxicities><Transcription><Transcription Elongation><Ubiquitin Ligase Component Gene><Ubiquitin Ligase Gene><Viral><Viral reservoir><Virus><Virus reservoir><Virus-HIV><Work><alpha(4)beta(7) integrin><anti-cancer therapy><anti-retroviral therapy><anti-retroviral treatment><antibody based therapies><antibody treatment><antibody-based therapeutics><antibody-based treatment><anticancer therapy><antiretroviral therapy><antiretroviral treatment><cancer therapy><cell biology><chronic disorder><chronic infection><collaboratory><developmental><drug/agent><effector T cell><exhaustion><experiment><experimental research><experimental study><faces><facial><host response><human immunodeficiency virus vaccine><humanized mice><humanized mouse><immune modulating agents><immune modulating drug><immune modulating therapeutics><immune modulatory agents><immune modulatory drugs><immune receptor><immunogen><immunomodulating agents><immunomodulatory agents><immunomodulatory drugs><immunomodulatory therapeutics><immunoresponse><in vivo imaging system><insight><integrin alpha4beta7><integrin α4β7><intestinal homing receptor alpha4beta7><langerin><latent virus infection><lymphocyte-Peyer's patch adhesion molecule><mRNA Export><malignancy><mouse model><multi-drug resistant><multidrug resistant><murine model><neoplasm/cancer><pandemic><pandemic disease><pathway><persistent infection><preference><reactivation from latency><receptor><resection><side effect><social role><structural biology><success><tat-Associated Kinase><therapeutic target><thymus derived lymphocyte><trafficking><ubiquitin ligase><viral rebound><virology><virus rebound><yeast protein>