18 results on '"Ansari, Aftab A."'
Search Results
2. Phenotypic and Functional Characterization of Monoclonal Antibodies with Specificity for Rhesus Macaque CD200, CD200R and Mincle
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Byrareddy, Siddappa N., primary, Little, Dawn, additional, Mayne, Ann E., additional, Villinger, Francois, additional, and Ansari, Aftab A., additional
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- 2015
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3. Identification of Potential Cytokine Pathways for Therapeutic Intervention in Murine Primary Biliary Cirrhosis
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Kawata, Kazuhito, primary, Tsuda, Masanobu, additional, Yang, Guo-Xiang, additional, Zhang, Weici, additional, Tanaka, Hajime, additional, Tsuneyama, Koichi, additional, Leung, Patrick, additional, He, Xiao-Song, additional, Knechtle, Stuart, additional, Ansari, Aftab A., additional, Coppel, Ross L., additional, and Gershwin, M. Eric, additional
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- 2013
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4. In Vivo Administration of a JAK3 Inhibitor to Chronically SIV Infected Rhesus Macaques Leads to NK Cell Depletion Associated with Transient Modest Increase in Viral Loads
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Takahashi, Yoshiaki, primary, Mayne, Ann E., additional, Khowawisetsut, Ladawan, additional, Pattanapanyasat, Kovit, additional, Little, Dawn, additional, Villinger, Francois, additional, and Ansari, Aftab A., additional
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- 2013
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5. Relationships between IL-17+ Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques
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Khowawisetsut, Ladawan, primary, Pattanapanyasat, Kovit, additional, Onlamoon, Nattawat, additional, Mayne, Ann E., additional, Little, Dawn M., additional, Villinger, Francois, additional, and Ansari, Aftab A., additional
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- 2013
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6. Re-Evaluation of PD-1 Expression by T Cells as a Marker for Immune Exhaustion during SIV Infection
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Hong, Jung Joo, primary, Amancha, Praveen K., additional, Rogers, Kenneth, additional, Ansari, Aftab A., additional, and Villinger, Francois, additional
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- 2013
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7. Multiploid CD61+ Cells Are the Pre-Dominant Cell Lineage Infected during Acute Dengue Virus Infection in Bone Marrow
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Clark, Kristina B., primary, Noisakran, Sansanee, additional, Onlamoon, Nattawat, additional, Hsiao, Hui-Mien, additional, Roback, John, additional, Villinger, Francois, additional, Ansari, Aftab A., additional, and Perng, Guey Chuen, additional
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- 2012
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8. Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II
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Zhang, Weici, primary, Tsuda, Masanobu, additional, Yang, Guo-Xiang, additional, Tsuneyama, Koichi, additional, He, Xiao-Song, additional, Ansari, Aftab A., additional, Ridgway, William M., additional, Coppel, Ross L., additional, Lian, Zhe-Xiong, additional, Leung, Patrick S.C., additional, and Gershwin, M. Eric, additional
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- 2012
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9. Protection of Macaques with Diverse MHC Genotypes against a Heterologous SIV by Vaccination with a Deglycosylated Live-Attenuated SIV
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Sugimoto, Chie, primary, Watanabe, Satoru, additional, Naruse, Taeko, additional, Kajiwara, Eiji, additional, Shiino, Teiichiro, additional, Umano, Natsuko, additional, Ueda, Kayoko, additional, Sato, Hirotaka, additional, Ohgimoto, Shinji, additional, Hirsch, Vanessa, additional, Villinger, Francois, additional, Ansari, Aftab A., additional, Kimura, Akinori, additional, Miyazawa, Masaaki, additional, Suzuki, Yasuo, additional, Yamamoto, Naoki, additional, Nagai, Yoshiyuki, additional, and Mori, Kazuyasu, additional
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- 2010
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10. In Vivo Administration of a JAK3 Inhibitor to Chronically SIV Infected Rhesus Macaques Leads to NK Cell Depletion Associated with Transient Modest Increase in Viral Loads.
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Takahashi, Yoshiaki, Mayne, Ann E., Khowawisetsut, Ladawan, Pattanapanyasat, Kovit, Little, Dawn, Villinger, Francois, and Ansari, Aftab A.
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MACAQUES ,CELL death ,IMMUNE response ,VIRUS diseases ,VIROLOGY ,COMMUNICABLE diseases ,DISEASES - Abstract
Innate immune responses are reasoned to play an important role during both acute and chronic SIV infection and play a deterministic role during the acute stages on the rate of infection and disease progression. NK cells are an integral part of the innate immune system but their role in influencing the course of SIV infection has been a subject of debate. As a means to delineate the effect of NK cells on SIV infection, use was made of a Janus kinase 3 (JAK3) inhibitor that has previously been shown to be effective in the depletion of NK cells in vivo in nonhuman primates (NHP). Extensive safety and in vitro/in vivo PK studies were conducted and an optimal dose that depletes NK cells and NK cell function in vivo identified. Six chronically SIV infected rhesus macaques, 3 with undetectable/low plasma viral loads and 3 with high plasma viral loads were administered a daily oral dose of 10 mg/kg for 35 days. Data obtained showed that, at the dose tested, the major cell lineage affected both in the blood and the GI tissues were the NK cells. Such depletion appeared to be associated with a transient increase in plasma and GI tissue viral loads. Whereas the number of NK cells returned to baseline values in the blood, the GI tissues remained depleted of NK cells for a prolonged period of time. Recent findings show that the JAK3 inhibitor utilized in the studies reported herein has a broader activity than previously reported with dose dependent effects on both JAK2 and JAK1 suggests that it is likely that multiple pathways are affected with the administration of this drug that needs to be taken into account. The findings reported herein are the first studies on the use of a JAK3 inhibitor in lentivirus infected NHP. [ABSTRACT FROM AUTHOR]
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- 2013
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11. Relationships between IL-17+ Subsets, Tregs and pDCs That Distinguish among SIV Infected Elite Controllers, Low, Medium and High Viral Load Rhesus Macaques.
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Khowawisetsut, Ladawan, Pattanapanyasat, Kovit, Onlamoon, Nattawat, Mayne, Ann E., Little, Dawn M., Villinger, Francois, and Ansari, Aftab A.
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SIMIAN immunodeficiency virus diseases ,INTERLEUKIN-17 ,VIRAL load ,RHESUS monkeys ,GASTROINTESTINAL system ,CD antigens ,DENDRITIC cells ,IMMUNOPATHOLOGY - Abstract
Comprehensive studies of the frequencies and absolute numbers of the various cell lineages that synthesize IL-17 in the blood and corresponding gastrointestinal (GI) tissues, their correlation with CD4
+ Tregs, CD8+ Tregs, total and IFN-α synthesizing plasmacytoid dendritic cells (pDC) relative to plasma viral load in SIV infection has been lacking. The unique availability of SIV infected rhesus macaques (RM) classified as Elite Controllers (EC), and those with Low, Intermediate and High Viral Loads (HVL) provided a unique opportunity to address this issue. Results of these studies showed that EC demonstrated a remarkable ability to reverse changes that are induced acutely by SIV in the various cell lineages. Highlights of the differences between EC and HVL RM within Gastro-intestinal tissues (GIT) was the maintenance and/or increases in the levels of IL-17 synthesizing CD4, CD8, and NK cells and pDCs associated with slight decreases in the levels of CD4+ Tregs and IFN-α synthesizing pDCs in EC as compared with decreases in the levels of IL-17 synthesizing CD4, CD8 and NK cells associated with increases in pDCs and IFN-α synthesizing pDCs in HVL monkeys. A previously underappreciated role for CD8+ Tregs was also noted with a moderate increase in ECs but further increases of CD8+ Tregs with increasing VL in viremic monkeys. Positive correlations between plasma VL and decreases in the levels of Th17, Tc17, NK-17, CD4+ Tregs and increases in the levels of CD8+ Tregs, total and IFN-α synthesizing pDCs were also noted. This study also identified 2 additional IL-17+ subsets in GIT as CD3−/ CD8+ /NKG2a− and CD3+ /CD8+ /NKG2a+ subsets. Studies also suggest a limited role for IFN-α synthesizing pDCs in chronic immune activation despite persistent up-regulation of ISGs. Finally, elevated persistent innate immune responses appear associated with poor prognosis. These findings provide an initial foundation for markers important to follow for vaccine design. [ABSTRACT FROM AUTHOR]- Published
- 2013
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12. Lymphoma-Like T Cell Infiltration in Liver Is Associated with Increased Copy Number of Dominant Negative Form of TGFβ Receptor II.
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Weici Zhang, Tsuda, Masanobu, Guo-Xiang Yang, Tsuneyama, Koichi, Xiao-Song He, Ansari, Aftab A., Ridgway, William M., Coppel, Ross L., Zhe-Xiong Lian, Leung, Patrick S. C., and Gershwin, M. Eric
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DNA repair ,FIBROBLASTS ,DNA polymerases ,ALKYLATING agents ,METHYL methanesulfonate ,DNA damage - Abstract
Hepatosplenic T cell lymphoma (HSTCL) is a distinct and lethal subtype of peripheral T cell lymphoma with an aggressive course and poor outcome despite multiagent chemotherapy. Contradictory literature, an unknown etiology, and poor response to treatment highlight the need to define the malignant process and identify molecular targets with potential for successful therapeutic interventions. Herein, we report that mice homozygously expressing a dominant negative TGFbRII (dnTGFbRII) under the control of the CD4 promoter spontaneously develop lymphoma-like T cell infiltration involving both spleen and liver. Splenomegaly, hepatomegaly and liver dysfunction were observed in homozygous dnTGFbRII mice between 10 weeks and 10 months of age associated with a predominant infiltration of CD4
- CD8- TCR*β+NK1.1+ or CD8+ TCRb+ NK1.1- T cell subsets. Notch 1 and c-Myc expression at the mRNA levels were significantly increased and positively correlated with the cell number of lymphoid infiltrates in the liver of dnTGFβRII homozygous compared to hemizygous mice. Further, 2x104 isolated lymphoma-like cells transplant disease by adoptive cell transfers. Collectively, our data demonstrate that increased copy number of dnTGFbRII is critical for development of lymphoma-like T cell infiltration. [ABSTRACT FROM AUTHOR]- Published
- 2012
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13. Distinct aging profiles of CD8+ T cells in blood versus gastrointestinal mucosal compartments
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Julie Elliott, Christina M. Ramirez, Lance E. Hultin, Otto O. Yang, Peter A. Anton, Rita B. Effros, Patricia M. Hultin, Beth D. Jamieson, Mary Ann Hausner, Jeffrey Dock, and Ansari, Aftab A
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0301 basic medicine ,Aging ,Physiology ,lcsh:Medicine ,CD38 ,CD8-Positive T-Lymphocytes ,Memory T cells ,Oral and gastrointestinal ,Cognition ,Learning and Memory ,0302 clinical medicine ,Cellular types ,Cytotoxic T cell ,Homeostasis ,IL-2 receptor ,Intestinal Mucosa ,lcsh:Science ,Cellular Senescence ,Multidisciplinary ,Immune cells ,CD28 ,Cell Differentiation ,Acquired immune system ,Flow Cytometry ,Body Fluids ,3. Good health ,Blood ,Cell Aging ,White blood cells ,Anatomy ,Research Article ,Cell biology ,Blood cells ,General Science & Technology ,Immunology ,T cells ,Cytotoxic T cells ,chemical and pharmacologic phenomena ,Biology ,Senescence ,Vaccine Related ,03 medical and health sciences ,Immune system ,Antigen ,Memory ,Clinical Research ,Humans ,Cell Proliferation ,Medicine and health sciences ,Biology and life sciences ,Inflammatory and immune system ,lcsh:R ,030104 developmental biology ,Animal cells ,Cognitive Science ,Immunization ,lcsh:Q ,Physiological Processes ,Organism Development ,CD8 ,Developmental Biology ,Neuroscience ,030215 immunology - Abstract
A hallmark of human immunosenescence is the accumulation of late-differentiated memory CD8+ T cells with features of replicative senescence, such as inability to proliferate, absence of CD28 expression, shortened telomeres, loss of telomerase activity, enhanced activation, and increased secretion of inflammatory cytokines. Importantly, oligoclonal expansions of these cells are associated with increased morbidity and mortality risk in elderly humans. Currently, most information on the adaptive immune system is derived from studies using peripheral blood, which contains approximately only 2% of total body lymphocytes. However, most lymphocytes reside in tissues. It is not clear how representative blood changes are of the total immune status. This is especially relevant with regard to the human gastrointestinal tract (GALT), a major reservoir of total body lymphocytes (approximately 60%) and an anatomical region of high antigenic exposure. To assess how peripheral blood T cells relate to those in other locations, we compare CD8+ T cells from peripheral blood and the GALT, specifically rectosigmoid colon, in young/middle age, healthy donors, focusing on phenotypic and functional alterations previously linked to senescence in peripheral blood. Overall, our results indicate that gut CD8+ T cells show profiles suggestive of greater differentiation and activation than those in peripheral blood. Specifically, compared to blood from the same individual, the gut contains significantly greater proportions of CD8+ T cells that are CD45RA- (memory), CD28-, CD45RA-CD28+ (early memory), CD45RA-CD28- (late memory), CD25-, HLA-DR+CD38+ (activated) and Ki-67+ (proliferating); ex vivo CD3+ telomerase activity levels are greater in the gut as well. However, gut CD8+ T cells may not necessarily be more senescent, since they expressed significantly lower levels of CD57 and PD-1 on CD45RO+ memory cells, and had in vitro proliferative dynamics similar to that of blood cells. Compartment-specific age-effects in this cohort were evident as well. Blood cells showed a significant increase with age in proportion of HLA-DR+38+, Ki-67+ and CD25+ CD8+ T cells; and an increase in total CD3+ ex-vivo telomerase activity that approached significance. By contrast, the only age-effect seen in the gut was a significant increase in CD45RA- (memory) and concurrent decrease in CD45RA+CD28+ (naïve) CD8+ T cells. Overall, these results indicate dynamics of peripheral blood immune senescence may not hold true in the gut mucosa, underscoring the importance for further study of this immunologically important tissue in evaluating the human immune system, especially in the context of chronic disease and aging.
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- 2017
14. Immune activation markers in peripartum women in Botswana: association with feeding strategy and maternal morbidity
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Elizabeth S. Russell, Laura M. Smeaton, Baitshepi Jorowe, Max Essex, Iain J. MacLeod, Risa M Hoffman, Shahin Lockman, Judith S. Currier, Sikhulile Moyo, Terence Mohammed, and Ansari, Aftab A
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Viral Diseases ,Multivariate analysis ,Maternal Health ,Breastfeeding ,lcsh:Medicine ,HIV Infections ,Reproductive health and childbirth ,Global Health ,Immunodeficiency Viruses ,Pregnancy ,Public and Occupational Health ,lcsh:Science ,2. Zero hunger ,Univariate analysis ,Botswana ,Multidisciplinary ,Obstetrics ,Postpartum Period ,Obstetrics and Gynecology ,Viral Load ,Prognosis ,Infant Formula ,Interleukin-10 ,3. Good health ,Breast Feeding ,Infectious Diseases ,Anti-Retroviral Agents ,Medical Microbiology ,Viral Pathogens ,Cytokines ,HIV/AIDS ,Gestation ,HIV clinical manifestations ,Female ,Viral load ,Research Article ,medicine.medical_specialty ,General Science & Technology ,Immunology ,Microbiology ,Fibrin Fibrinogen Degradation Products ,Interferon-gamma ,Clinical Research ,Virology ,Peripartum Period ,medicine ,Humans ,Microbial Pathogens ,Medicine and health sciences ,Tumor Necrosis Factor-alpha ,Interleukin-6 ,Proportional hazards model ,business.industry ,Prevention ,Inflammatory and immune system ,lcsh:R ,Infant, Newborn ,Biology and Life Sciences ,HIV ,Infant ,Molecular Development ,Newborn ,medicine.disease ,Diagnostic medicine ,CD4 Lymphocyte Count ,Immune System ,Multivariate Analysis ,Women's Health ,Clinical Immunology ,lcsh:Q ,business ,Breast feeding ,Developmental Biology - Abstract
Hormone levels shift the immune state in HIV-uninfected pregnant and breastfeeding women away from Th1 responses and toward regulation to permit fetal tolerance. Limited data exist on inflammation during pregnancy or postpartum in HIV-infected women, though certain inflammatory markers are associated with adverse health outcomes among HIV-infected persons. We measured hsCRP, D-dimer, IFN-γ, IL-6, IL-10 and TNF-α at 34 weeks gestation and six months postpartum in HIV-infected women from the Botswana Mashi PMTCT trial who were randomized to breastfeeding or formula-feeding. Differences in inflammatory markers between gestation and postpartum periods, and by randomized feeding method, were estimated using generalized estimating equations, adjusting for baseline plasma HIV-1 viral load, CD4 count, calendar time, and antiretroviral treatment status. Additionally, we studied the association between marker concentrations at six months postpartum and major adverse clinical events over the following 4.5 years, using case-cohort sampling and adjusted Cox proportional hazards models. In 86 breastfeeding and 75 formula-feeding women, hsCRP and D-dimer decreased significantly between 34 weeks gestation and six months postpartum, while IFN-γ increased. There was no significant association between inflammatory marker change and randomized feeding method after adjusting for multiple comparisons and removing outliers. In univariate analysis, TNF-α, D-dimer, and IFN-γ concentrations at six months postpartum were significant predictors of subsequent clinical events, and TNF-α remained significant in multivariate analysis (HR = 4.16, p = 0.001). In young HIV-infected women in Botswana inflammatory marker concentrations did not differ significantly between women who breast- vs. formula-fed. However, postpartum TNF-α level was predictive of subsequent adverse clinical event.
- Published
- 2014
15. Allo-reactivity of mesenchymal stem cells in rhesus macaques is dose and haplotype dependent and limits durable cell engraftment in vivo
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Kate C. Baker, Julie Bruhn, Iryna A. Isakova, Donald G. Phinney, Marcelo J. Kuroda, Veena Krishnappa, Calvin Lanclos, and Ansari, Aftab A
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Male ,Neutrophils ,Lymphocyte ,lcsh:Medicine ,Adaptive Immunity ,Immune Privilege ,Regenerative Medicine ,Major Histocompatibility Complex ,0302 clinical medicine ,Stem Cell Research - Nonembryonic - Human ,Killer Cells ,Bone Marrow and Stem Cell Transplantation ,lcsh:Science ,Immune Response ,0303 health sciences ,B-Lymphocytes ,Multidisciplinary ,biology ,Stem Cells ,Graft Survival ,Animal Models ,Hematology ,Natural killer T cell ,Innate Immunity ,Killer Cells, Natural ,Adult Stem Cells ,medicine.anatomical_structure ,Natural ,Medicine ,Stem Cell Research - Nonembryonic - Non-Human ,Female ,Development of treatments and therapeutic interventions ,Macaque ,Biotechnology ,Research Article ,Homologous ,General Science & Technology ,T cell ,Immunology ,Major histocompatibility complex ,Mesenchymal Stem Cell Transplantation ,03 medical and health sciences ,Immune system ,Model Organisms ,MHC class I ,medicine ,Immune Tolerance ,Animals ,Transplantation, Homologous ,Lymphocyte Count ,Biology ,030304 developmental biology ,Cell Proliferation ,Transplantation ,5.2 Cellular and gene therapies ,Inflammatory and immune system ,Mesenchymal stem cell ,Histocompatibility Antigens Class I ,lcsh:R ,Histocompatibility Antigens Class II ,Immunity ,Mesenchymal Stem Cells ,Immunologic Subspecialties ,Stem Cell Research ,Macaca mulatta ,Haplotypes ,biology.protein ,Natural Killer T-Cells ,lcsh:Q ,Lymph Nodes ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
The emerging paradigm that MSCs are immune privileged has fostered the use of "off-the-shelf" allogeneic MSC-based therapies in human clinical trials. However, this approach ignores studies in experimental animals wherein transplantation of MSCs across MHC boundaries elicits measurable allo-immune responses. To determine if MSCs are hypo-immunogeneic, we characterized the immune response in rhesus macaques following intracranial administration of allogeneic vs. autologous MSCs. This analysis revealed unambiguous evidence of productive allo-recognition based on expansion of NK, B and T cell subsets in peripheral blood and detection of allo-specific antibodies in animals administered allogeneic but not autologous MSCs. Moreover, the degree of MHC class I and II mismatch between the MSC donor and recipient significantly influenced the magnitude and nature of the allo-immune response. Consistent with these findings, real-time PCR analysis of brain tissue from female recipients administered varying doses of male, allogeneic MSCs revealed a significant inverse correlation between MSC engraftment levels and cell dose. Changes in post-transplant neutrophil and lymphocyte counts also correlated with dose and were predictive of overall MSC engraftment levels. However, secondary antigen challenge failed to elicit a measurable immune response in allogeneic recipients. Finally, extensive behavior testing of animals revealed no main effect of cell dose on motor skills, social development, or temperament. Collectively, these data indicate that allogeneic MSCs are weakly immunogenic when transplanted across MHC boundaries in rhesus macaques and this negatively impacts durable engraftment levels. Therefore the use of unrelated donor MSCs should be carefully evaluated in human patients.
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- 2014
16. Viral RNA levels and env variants in semen and tissues of mature male rhesus macaques infected with SIV by penile inoculation
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Zhong-Min Ma, Linda Fritts, Christopher J. Miller, Francis Fieni, Mars Stone, Joseph Dutra, and Ansari, Aftab A
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Male ,Urologic Diseases ,Axillary lymph nodes ,General Science & Technology ,viruses ,Molecular Sequence Data ,Simian Acquired Immunodeficiency Syndrome ,lcsh:Medicine ,Semen ,Biology ,medicine.disease_cause ,Semen collection ,03 medical and health sciences ,Seminal vesicle ,Viral entry ,Blood plasma ,medicine ,Animals ,Gene Products ,Viral ,lcsh:Science ,Lymph node ,Phylogeny ,030304 developmental biology ,0303 health sciences ,env ,Multidisciplinary ,Base Sequence ,030306 microbiology ,lcsh:R ,Simian immunodeficiency virus ,Gene Products, env ,Virology ,Macaca mulatta ,3. Good health ,medicine.anatomical_structure ,Infectious Diseases ,Good Health and Well Being ,Organ Specificity ,RNA, Viral ,RNA ,HIV/AIDS ,Simian Immunodeficiency Virus ,lcsh:Q ,Infection ,Research Article ,Penis - Abstract
HIV is shed in semen but the anatomic site of virus entry into the genital secretions is unknown. We determined viral RNA (vRNA) levels and the envelope gene sequence in the SIVmac 251 viral populations in the genital tract and semen of 5 adult male rhesus monkeys (Macaca mulatta) that were infected after experimental penile SIV infection. Paired blood and semen samples were collected from 1-9 weeks after infection and the monkeys were necropsied eleven weeks after infection. The axillary lymph nodes, testes, epididymis, prostate, and seminal vesicles were collected and vRNA levels and single-genome analysis of the SIVmac251 env variants was performed. At the time of semen collection, blood vRNA levels were between 3.09 and 7.85 log10 vRNA copies/ml plasma. SIV RNA was found in the axillary lymph nodes of all five monkeys and in 3 of 5 monkeys, all tissues examined were vRNA positive. In these 3 monkeys, vRNA levels (log10 SIVgag copies/ug of total tissue RNA) in the axillary lymph node (6.48 ± 0.50) were significantly higher than in the genital tract tissues: testis (3.67 ± 2.16; p
- Published
- 2013
17. In captive rhesus macaques, cervicovaginal inflammation is common but not associated with the stable polymicrobial microbiome
- Author
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Kristina Rothaeulser, Linda Fritts, Gregory T. Spear, Patrick M. Gillevet, Christopher J. Miller, and Ansari, Aftab A
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lcsh:Medicine ,medicine.disease_cause ,Macaque ,Laboratory ,0302 clinical medicine ,Models ,Lactobacillus ,Prevalence ,030212 general & internal medicine ,lcsh:Science ,0303 health sciences ,Multidisciplinary ,biology ,Coinfection ,Monkey Diseases ,Obstetrics and Gynecology ,Infectious Diseases ,HIV/AIDS ,Cytokines ,Medicine ,Tumor necrosis factor alpha ,Female ,medicine.symptom ,Inflammation Mediators ,Research Article ,General Science & Technology ,Clinical Research Design ,Inflammation ,Models, Biological ,Microbiology ,Proinflammatory cytokine ,03 medical and health sciences ,Bacterial Vaginosis ,biology.animal ,Animals, Laboratory ,Virology ,medicine ,Animals ,Microbiome ,Animal Models of Disease ,Vaginitis ,Biology ,030304 developmental biology ,Genitourinary Infections ,Inflammatory and immune system ,lcsh:R ,Immunity ,HIV ,Simian immunodeficiency virus ,Biological ,medicine.disease ,biology.organism_classification ,Macaca mulatta ,Uterine Cervicitis ,Animal Models of Infection ,Immunology ,Metagenome ,lcsh:Q ,Clinical Immunology - Abstract
Vaginal inoculation of rhesus macaques (RM) with simian immunodeficiency virus (SIV) has been used to study the biology of HIV transmission. Although the results of vaginal SIV transmission experiments could be affected by vaginal inflammation, studies to date have been conducted without regard to levels of pre-existing genital inflammation present in RM. We collected cevicovaginal secretions (CVS) from 33-36 RM during the mid menstrual cycle (day 10-20) at 2 time points approximately 8 months apart and characterized the mRNA and protein levels of inflammatory cytokines, chemokines and interferon-stimulated genes. There was extreme variability in the levels of inflammatory mediators (IFN-α, IFN-γ, IL-6, TNF, IL-1b, IP-10, MIG, IL-12 and IL-17). In most animals, the mRNA levels of the inflammatory mediators were similar in the 2 CVS samples collected 8 months apart, suggesting that genital inflammation is stable in a subset of captive female RM. At both time points the cervicovaginal microbiota had low levels of Lactobacillus and was relatively diverse with an average of 13 genera in the samples from the first time point (median 13, range 7-21) and an average of 11.5 genera in the samples from the second time point (median 11, range 5-20). Many of the macaques had similar microbiota in the samples collected 8 months apart. However, we found no correlation between specific bacterial genera and the mRNA or protein levels of the inflammatory mediators in the genital tract of RM in this study. It seems likely that results of published vaginal SIV transmission experiments in RM have been influenced by pre-existing inflammation in the animals used for the experiments.
- Published
- 2012
18. Anti-HIV Antibody Responses and the HIV Reservoir Size during Antiretroviral Therapy
- Author
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Peter D. Burbelo, Nicolas Chomont, Janet D. Siliciano, Sharon R Lewin, Sulggi A. Lee, Una O'Doherty, Steven A. Yukl, Steven G. Deeks, Douglas D. Richman, Sarah Palmer, Rémi Fromentin, Peter Bacchetti, and Ansari, Aftab A
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Male ,Antibody Response ,Artificial Gene Amplification and Extension ,HIV Infections ,HIV Integrase ,HIV Antibodies ,Pathology and Laboratory Medicine ,Biochemistry ,Polymerase Chain Reaction ,law.invention ,Immunodeficiency Viruses ,Animal Cells ,Medicine ,Digital polymerase chain reaction ,RNA structure ,lcsh:Science ,Immune Response ,Precipitation Techniques ,3. Good health ,Nucleic acids ,5.1 Pharmaceuticals ,Medical Microbiology ,Viral Pathogens ,HIV/AIDS ,Development of treatments and therapeutic interventions ,Cellular Types ,Antibody ,Infection ,Viral load ,Immune Cells ,RNA Splicing ,Immunology ,030106 microbiology ,Microbiology ,03 medical and health sciences ,Clinical Research ,Genetics ,Humans ,RNA folding ,Molecular Biology Techniques ,Microbial Pathogens ,Molecular Biology ,Blood Cells ,lcsh:R ,Organisms ,Biology and Life Sciences ,Proteins ,RNA ,DNA ,Virology ,030104 developmental biology ,DNA, Viral ,HIV-1 ,lcsh:Q ,RNA viruses ,CD4-Positive T-Lymphocytes ,0301 basic medicine ,Physiology ,lcsh:Medicine ,White Blood Cells ,law ,Immune Physiology ,Antiretroviral Therapy, Highly Active ,Medicine and Health Sciences ,Viral ,Polymerase chain reaction ,Immune System Proteins ,Multidisciplinary ,biology ,T Cells ,Middle Aged ,Viral Load ,Integrase ,Intestines ,Infectious Diseases ,Real-time polymerase chain reaction ,Viruses ,RNA, Viral ,Female ,Pathogens ,Biotechnology ,Research Article ,General Science & Technology ,Anti-HIV Agents ,Antiretroviral Therapy ,Research and Analysis Methods ,Antibodies ,Virus ,MD Multidisciplinary ,Retroviruses ,Immunoprecipitation ,Highly Active ,business.industry ,Lentivirus ,HIV ,Cell Biology ,CD4 Lymphocyte Count ,Macromolecular structure analysis ,biology.protein ,Lymph Nodes ,business - Abstract
Author(s): Lee, Sulggi A; Bacchetti, Peter; Chomont, Nicolas; Fromentin, Remi; Lewin, Sharon R; O'Doherty, Una; Palmer, Sarah; Richman, Douglas D; Siliciano, Janet D; Yukl, Steven A; Deeks, Steven G; Burbelo, Peter D | Abstract: BackgroundA major challenge to HIV eradication strategies is the lack of an accurate measurement of the total burden of replication-competent HIV (the "reservoir"). We assessed the association of anti-HIV antibody responses and the estimated size of the reservoir during antiretroviral therapy (ART).MethodsWe evaluated anti-HIV antibody profiles using luciferase immunoprecipitation systems (LIPS) assay in relation to several blood-based HIV reservoir measures: total and 2-LTR DNA (rtPCR or droplet digital PCR); integrated DNA (Alu PCR); unspliced RNA (rtPCR), multiply-spliced RNA (TILDA), residual plasma HIV RNA (single copy PCR), and replication-competent virus (outgrowth assay). We also assessed total HIV DNA and RNA in gut-associated lymphoid tissue (rtPCR). Spearman correlations and linear regressions were performed using log-transformed blood- or tissue-based reservoir measurements as predictors and log-transformed antibody levels as outcome variables.ResultsAmong 51 chronically HIV-infected ART-suppressed participants (median age = 57, nadir CD4+ count = 196 cells/mm3, ART duration = 9 years), the most statistically significant associations were between antibody responses to integrase and HIV RNA in gut-associated lymphoid tissue (1.17 fold-increase per two-fold RNA increase, P = 0.004) and between antibody responses to matrix and integrated HIV DNA in resting CD4+ T cells (0.35 fold-decrease per two-fold DNA increase, P = 0.003). However, these associations were not statistically significant after a stringent Bonferroni-adjustment of Pl0.00045. Multivariate models including age and duration of ART did not markedly alter results.ConclusionsOur findings suggest that anti-HIV antibody responses may reflect the size of the HIV reservoir during chronic treated HIV disease, possibly via antigen recognition in reservoir sites. Larger, prospective studies are needed to validate the utility of antibody levels as a measure of the total body burden of HIV during treatment.
- Published
- 2016
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