Rate of AIDS progression is associated with gastrointestinal dysfunction in simian immunodeficiency virus-infected pigtail macaques. 2013

Lauren A Canary, and Carol L Vinton, and David R Morcock, and Jordan B Pierce, and Jacob D Estes, and Jason M Brenchley, and Nichole R Klatt
Laboratory of Molecular Microbiology, Program in Barrier Immunity and Repair, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

During HIV/SIV infection, mucosal immune system dysfunction and systemic immune activation are associated with progression to AIDS; however, it is unclear to what extent pre-existing gastrointestinal damage relates to disease progression postinfection. Pigtail macaques (PTM) are an excellent model in which to assess mucosal dysfunction in relation to HIV/SIV pathogenesis, as the majority of these animals have high levels of gastrointestinal damage, immune activation, and microbial translocation prior to infection, and rapidly progress to AIDS upon SIV infection. In this study, we characterized the mucosal immune environment prior to and throughout SIV infection in 13 uninfected PTM and 9 SIV-infected PTM, of which 3 were slow progressors. This small subset of slow progressors had limited innate immune activation in mucosal tissues in the periphery, which was associated with a more intact colonic epithelial barrier. Furthermore, we found that preinfection levels of microbial translocation, as measured by LPS-binding protein, in PTM correlated with the rate of progression to AIDS. These data suggest that pre-existing levels of microbial translocation and gastrointestinal tract dysfunction may influence the rate of HIV disease progression.

UI MeSH Term Description Entries
D007413 Intestinal Mucosa Lining of the INTESTINES, consisting of an inner EPITHELIUM, a middle LAMINA PROPRIA, and an outer MUSCULARIS MUCOSAE. In the SMALL INTESTINE, the mucosa is characterized by a series of folds and abundance of absorptive cells (ENTEROCYTES) with MICROVILLI. Intestinal Epithelium,Intestinal Glands,Epithelium, Intestinal,Gland, Intestinal,Glands, Intestinal,Intestinal Gland,Mucosa, Intestinal
D008254 Macaca nemestrina A species of the genus MACACA which inhabits Malaya, Sumatra, and Borneo. It is one of the most arboreal species of Macaca. The tail is short and untwisted. M. leonina,Macaca nemestrina leonina,Macaca nemestrina pagensis,Macaca nemestrina siberu,Macaca siberu,Monkey, Pig-Tailed,Pagai Macaque,Pig-Tail Macaque,Pig-Tailed Macaque,Pig-Tailed Monkey,M. pagensis,Macaca pagensis,Monkey, Pigtail,Monkey, Pigtailed,Pigtail Macaque,Macaque, Pagai,Macaque, Pig-Tail,Macaque, Pig-Tailed,Macaque, Pigtail,Monkey, Pig Tailed,Pagai Macaques,Pig Tail Macaque,Pig Tailed Macaque,Pig Tailed Monkey,Pig-Tail Macaques,Pig-Tailed Macaques,Pig-Tailed Monkeys,Pigtail Macaques,Pigtail Monkey,Pigtail Monkeys,Pigtailed Monkey,Pigtailed Monkeys
D004195 Disease Models, Animal Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases. Animal Disease Model,Animal Disease Models,Disease Model, Animal
D005767 Gastrointestinal Diseases Diseases in any segment of the GASTROINTESTINAL TRACT from ESOPHAGUS to RECTUM. Cholera Infantum,Gastrointestinal Disorders,Functional Gastrointestinal Disorders,Gastrointestinal Disorders, Functional,Disease, Gastrointestinal,Diseases, Gastrointestinal,Functional Gastrointestinal Disorder,Gastrointestinal Disease,Gastrointestinal Disorder,Gastrointestinal Disorder, Functional
D000163 Acquired Immunodeficiency Syndrome An acquired defect of cellular immunity associated with infection by the human immunodeficiency virus (HIV), a CD4-positive T-lymphocyte count under 200 cells/microliter or less than 14% of total lymphocytes, and increased susceptibility to opportunistic infections and malignant neoplasms. Clinical manifestations also include emaciation (wasting) and dementia. These elements reflect criteria for AIDS as defined by the CDC in 1993. AIDS,Immunodeficiency Syndrome, Acquired,Immunologic Deficiency Syndrome, Acquired,Acquired Immune Deficiency Syndrome,Acquired Immuno-Deficiency Syndrome,Acquired Immuno Deficiency Syndrome,Acquired Immuno-Deficiency Syndromes,Acquired Immunodeficiency Syndromes,Immuno-Deficiency Syndrome, Acquired,Immuno-Deficiency Syndromes, Acquired,Immunodeficiency Syndromes, Acquired,Syndrome, Acquired Immuno-Deficiency,Syndrome, Acquired Immunodeficiency,Syndromes, Acquired Immuno-Deficiency,Syndromes, Acquired Immunodeficiency
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013997 Time Factors Elements of limited time intervals, contributing to particular results or situations. Time Series,Factor, Time,Time Factor
D015302 Simian Immunodeficiency Virus Species of the genus LENTIVIRUS, subgenus primate immunodeficiency viruses (IMMUNODEFICIENCY VIRUSES, PRIMATE), that induces acquired immunodeficiency syndrome in monkeys and apes (SAIDS). The genetic organization of SIV is virtually identical to HIV. SIV (Simian immunodeficiency virus),Immunodeficiency Viruses, Simian,Simian Immunodeficiency Viruses,Immunodeficiency Virus, Simian
D016097 Simian Acquired Immunodeficiency Syndrome Acquired defect of cellular immunity that occurs naturally in macaques infected with SRV serotypes, experimentally in monkeys inoculated with SRV or MASON-PFIZER MONKEY VIRUS; (MPMV), or in monkeys infected with SIMIAN IMMUNODEFICIENCY VIRUS. AIDS, Simian,SAIDS,Simian AIDS,Simian Acquired Immune Deficiency Syndrome,Simian Acquired Immuno-Deficiency Syndrome,AIDSs, Simian,Simian AIDSs,Simian Acquired Immuno Deficiency Syndrome
D018450 Disease Progression The worsening and general progression of a disease over time. This concept is most often used for chronic and incurable diseases where the stage of the disease is an important determinant of therapy and prognosis. Clinical Course,Clinical Progression,Disease Exacerbation,Exacerbation, Disease,Progression, Clinical,Progression, Disease

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