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https://www.readbyqxmd.com/read/28081037/higher-cd163-levels-are-associated-with-insulin-resistance-in-hepatitis-c-virus-infected-and-hiv-infected-adults
#1
Michael Reid, Yifei Ma, Rebecca Scherzer, Jennifer C Price, Audrey L French, Michael W Plankey, Carl Grunfeld, Phyllis C Tien
OBJECTIVES: HIV/hepatitis C virus (HCV) coinfection is associated with insulin resistance, but the mechanism is unclear. We hypothesized that intestinal epithelial damage and the consequent monocyte/macrophage activation and inflammation explain this perturbation. DESIGN: Cross-sectional study of 519 adults (220 HIV+/HCV-; 64 HIV-/HCV+; 89 HIV+/HCV+; 146 HIV-/HCV-). METHODS: We used multivariable linear regression to evaluate associations of HIV and HCV with the homeostasis model assessment of insulin resistance (HOMA-IR) and if intestinal fatty (FA) acid binding protein (I-FABP, a marker of gut epithelial integrity), soluble CD14 (sCD14) and soluble CD163 (sCD163) (markers of monocyte/macrophage activation), and IL-6 (an inflammatory cytokine) mediated this association...
January 28, 2017: AIDS
https://www.readbyqxmd.com/read/28069756/inside-out-hiv-the-gut-microbiome-and-the-mucosal-immune-system
#2
REVIEW
Jay Liu, Brett Williams, Daniel Frank, Stephanie M Dillon, Cara C Wilson, Alan L Landay
The components of the human gut microbiome have been found to influence a broad array of pathologic conditions ranging from heart disease to diabetes and even to cancer. HIV infection upsets the delicate balance in the normal host-microbe interaction both through alterations in the taxonomic composition of gut microbial communities as well as through disruption of the normal host response mechanisms. In this article we review the current methods of gut microbiome analysis and the resulting data regarding how HIV infection might change the balance of commensal bacteria in the gut...
January 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28056224/recombinant-fowlpox-virus-vector-based-vaccines-expression-kinetics-dissemination-and-safety-profile-following-intranasal-delivery
#3
David G Townsend, Shubhanshi Trivedi, Ronald J Jackson, Charani Ranasinghe
We have previously established that mucosal uptake of recombinant fowlpox virus (rFPV) vaccines is far superior to other vector-based vaccines. Specifically, intranasal (i.n.) priming with rFPV vaccines can recruit unique antigen presenting cells (APC), which induce excellent mucosal and systemic HIV-specific CD8+ T cell immunity. In this study, we have for the first time investigated the in-vivo dissemination, safety and expression kinetics of rFPV post i.n. delivery using recombinant viruses expressing green fluorescent protein (GFP) or mCherry...
January 5, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28036372/collapse-of-cytolytic-potential-in-siv-specific-cd8-t-cells-following-acute-siv-infection-in-rhesus-macaques
#4
Emily R Roberts, Diane G Carnathan, Hui Li, George M Shaw, Guido Silvestri, Michael R Betts
Poor maintenance of cytotoxic factor expression among HIV-specific CD8+ T cells, in part caused by dysregulated expression of the transcription factor T-bet, is associated with HIV disease progression. However, the precise evolution and context in which CD8+ T cell cytotoxic functions become dysregulated in HIV infection remain unclear. Using the rhesus macaque (RM) SIV infection model, we evaluated the kinetics of SIV-specific CD8+ T cell cytolytic factor expression in peripheral blood, lymph node, spleen, and gut mucosa from early acute infection through chronic infection...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/28002063/low-abundance-of-colonic-butyrate-producing-bacteria-in-hiv-infection-is-associated-with-microbial-translocation-and-immune-activation
#5
Stephanie M Dillon, Jon Kibbie, Eric J Lee, Kejun Guo, Mario L Santiago, Gregory L Austin, Sara Gianella, Alan L Landay, Andrew M Donovan, Daniel N Frank, Martin D McCarter, Cara C Wilson
OBJECTIVE: Gut microbial translocation (MT) is a major driving force behind chronic immune activation during HIV-1 infection. HIV-1-related intestinal dysbiosis, including increases in mucosa-associated pathobionts, may influence MT and contribute to mucosal and systemic inflammation. Thus, it is critical to understand the mechanisms by which gut microbes and their metabolic products, such as butyrate, influence immune cell function during HIV-1 infection. DESIGN: A cross-sectional study was performed to compare the relative abundance of butyrate-producing bacterial species (BPB) in colonic biopsies and stool of untreated, chronic HIV-1 infected (n = 18) and uninfected (n = 14) study participants...
December 19, 2016: AIDS
https://www.readbyqxmd.com/read/28000678/the-effects-of-prebiotics-on-microbial-dysbiosis-butyrate-production-and-immunity-in-hiv-infected-subjects
#6
S Serrano-Villar, J F Vázquez-Castellanos, A Vallejo, A Latorre, T Sainz, S Ferrando-Martínez, D Rojo, J Martínez-Botas, J Del Romero, N Madrid, M Leal, J I Mosele, M J Motilva, C Barbas, M Ferrer, A Moya, S Moreno, M J Gosalbes, V Estrada
Altered interactions between the gut mucosa and bacteria during HIV infection seem to contribute to chronic immune dysfunction. A deeper understanding of how nutritional interventions could ameliorate gut dysbiosis is needed. Forty-four subjects, including 12 HIV(+) viremic untreated (VU) patients, 23 antiretroviral therapy-treated (ART(+)) virally suppressed patients (15 immunological responders and 8 non-responders) and 9 HIV(-) controls (HIV(-)), were blindly randomized to receive either prebiotics (scGOS/lcFOS/glutamine) or placebo (34/10) over 6 weeks in this pilot study...
December 21, 2016: Mucosal Immunology
https://www.readbyqxmd.com/read/27986871/hiv-infection-of-kupffer-cells-results-in-an-amplified-proinflammatory-response-to-lps
#7
Arevik Mosoian, Lumin Zhang, Feng Hong, Francesc Cunyat, Adeeb Rahman, Riti Bhalla, Ankur Panchal, Yedidya Saiman, M Isabel Fiel, Sander Florman, Sasan Roayaie, Myron Schwartz, Andrea Branch, Mario Stevenson, Meena B Bansal
End-stage liver disease is a common cause of non-AIDS-related mortality in HIV(+) patients, despite effective anti-retroviral therapies (ARTs). HIV-1 infection causes gut CD4 depletion and is thought to contribute to increased gut permeability, bacterial translocation, and immune activation. Microbial products drain from the gut into the liver via the portal vein where Kupffer cells (KCs), the resident liver macrophage, clear translocated microbial products. As bacterial translocation is implicated in fibrogenesis in HIV patients through unclear mechanisms, we tested the hypothesis that HIV infection of KCs alters their response to LPS in a TLR4-dependent manner...
December 16, 2016: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/27959961/persistent-low-level-replication-of-siv%C3%AE-nef-drives-maturation-of-antibody-and-cd8-t-cell-responses-to-induce-protective-immunity-against-vaginal-siv-infection
#8
Sama Adnan, R Keith Reeves, Jacqueline Gillis, Fay E Wong, Yi Yu, Jeremy V Camp, Qingsheng Li, Michelle Connole, Yuan Li, Michael Piatak, Jeffrey D Lifson, Wenjun Li, Brandon F Keele, Pamela A Kozlowski, Ronald C Desrosiers, Ashley T Haase, R Paul Johnson
Defining the correlates of immune protection conferred by SIVΔnef, the most effective vaccine against SIV challenge, could enable the design of a protective vaccine against HIV infection. Here we provide a comprehensive assessment of immune responses that protect against SIV infection through detailed analyses of cellular and humoral immune responses in the blood and tissues of rhesus macaques vaccinated with SIVΔnef and then vaginally challenged with wild-type SIV. Despite the presence of robust cellular immune responses, animals at 5 weeks after vaccination displayed only transient viral suppression of challenge virus, whereas all macaques challenged at weeks 20 and 40 post-SIVΔnef vaccination were protected, as defined by either apparent sterile protection or significant suppression of viremia in infected animals...
December 2016: PLoS Pathogens
https://www.readbyqxmd.com/read/27941355/managing-nonalcoholic-fatty-liver-disease-in-patients-living-with-hiv
#9
Zaid H Tafesh, Elizabeth C Verna
PURPOSE OF REVIEW: Nonalcoholic fatty liver disease (NAFLD) is common among patients living with HIV and may lead to liver-related morbidity and mortality. RECENT FINDINGS: The prevalence of NAFLD among patients with HIV is increasingly well described due to new noninvasive techniques to quantify hepatic steatosis and fibrosis. Patients with HIV may be at increased risk of disease progression, though high-quality natural history studies are not available. The high rates of metabolic syndrome, dyslipidemia and insulin resistance may partially account for this excess risk, though the impact of HIV itself, antiretroviral medications and dysregulation of the gut-liver axis likely play important roles...
February 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/27932619/ontogeny-of-cd4-t-lymphocytes-with-phenotypic-susceptibility-to-hiv-1-during-exclusive-and-non-exclusive-breastfeeding-in-hiv-1-exposed-ugandan-infants
#10
Elizabeth J McFarland, Tina M Powell, Carolyne Onyango-Makumbi, Weiming Zhang, Kelsey Melander, Prossy Naluyima, Samuel Okurut, Michael A Eller, Mary Glenn Fowler, Edward N Janoff
BACKGROUND: Among HIV-1-exposed infants, mixed breastfeeding is associated with higher postnatal HIV-1 transmission than exclusive breastfeeding, but the mechanisms of this differential risk are uncertain. METHODS: HIV-1-exposed, Ugandan infants were prospectively assessed over the first year of life for feeding practices and T cell maturation, intestinal homing (β7(hi)), activation, and HIV-1 co-receptor (CCR5) expression in peripheral blood. Infants receiving only breast milk and those with introduction of other foods prior to 6 months, categorized as exclusive and non-exclusive, respectively...
December 8, 2016: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/27928019/tlr2-ligation-enhances-hiv-1-replication-in-activated-ccr6-cd4-t-cells-by-increasing-virus-entry-and-establishing-a-more-permissive-environment-to-infection
#11
Jean-François Bolduc, Michel Ouellet, Laurent Hany, Michel J Tremblay
: In this study, we investigated the effect of TLR2 ligation on the permissiveness of activated CD4(+) T cells to HIV-1 infection by focusing our experiments on the relative susceptibility of cell subsets based on their expression of CCR6. Purified primary human CD4(+) T cells were first subjected to a CD3/CD28 costimulation before treatment with the TLR2 agonist Pam3CSK4. Finally, cells were inoculated with R5-tropic HIV-1 particles that permit to study the effect of TLR2 triggering on virus production at both population and single-cell levels...
December 7, 2016: Journal of Virology
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#12
Christine Oswald, Mathieu Rappas, James Kean, Andrew S Doré, James C Errey, Kirstie Bennett, Francesca Deflorian, John A Christopher, Ali Jazayeri, Jonathan S Mason, Miles Congreve, Robert M Cooke, Fiona H Marshall
Chemokines and their G-protein-coupled receptors play a diverse role in immune defence by controlling the migration, activation and survival of immune cells. They are also involved in viral entry, tumour growth and metastasis and hence are important drug targets in a wide range of diseases. Despite very significant efforts by the pharmaceutical industry to develop drugs, with over 50 small-molecule drugs directed at the family entering clinical development, only two compounds have reached the market: maraviroc (CCR5) for HIV infection and plerixafor (CXCR4) for stem-cell mobilization...
December 15, 2016: Nature
https://www.readbyqxmd.com/read/27925857/analysis-of-the-intestinal-microbial-community-and-inferred-functional-capacities-during-the-host-response-to-pneumocystis-pneumonia
#13
Derrick R Samuelson, Tysheena P Charles, Nicholas M de la Rua, Christopher M Taylor, Eugene E Blanchard, Meng Luo, Judd E Shellito, David A Welsh
BACKGROUND: Pneumocystis pneumonia is a major cause of morbidity and mortality in patients infected with HIV/AIDS. In this study, we evaluated the intestinal microbial communities associated with the development of experimental Pneumocystis pneumonia, as there is growing evidence that the intestinal microbiota is critical for host defense against fungal pathogens. METHODS: C57BL/6 mice were infected with live Pneumocystis murina (P. murina) via intratracheal inoculation and sacrificed 7 and 14 days postinfection for microbiota analysis...
December 7, 2016: Experimental Lung Research
https://www.readbyqxmd.com/read/27922858/hiv-hpv-and-microbiota-partners-in-crime
#14
Sergio Serrano-Villar, Emilia Vásquez-Domínguez, José Antonio Pérez-Molina, Talía Sainz, Amparo de Benito, Amparo Latorre, Andrés Moya, María José Gosalbes, Santiago Moreno
Altered interplay between gut mucosa and dysbiotic bacteria during HIV infection seems to fuel chronic immune dysfunction and might explain the excess rates of HPV-associated anal cancer in HIV-infected individuals. Here, we show in HIV-infected MSM undergoing screening for HPV-related cancer that specific fecal and mucosal bacteria are able to predict the existence of precancerous anal lesions. If confirmed, these bacterial biomarkers could be exploited either as diagnostic tools or therapeutic targets.
December 5, 2016: AIDS
https://www.readbyqxmd.com/read/27922852/hiv-associated-changes-in-the-enteric-microbial-community-potential-role-in-loss-of-homeostasis-and-development-of-systemic-inflammation
#15
David B Gootenberg, Jeffrey M Paer, Jesus-Mario Luevano, Douglas S Kwon
PURPOSE OF REVIEW: Despite HIV therapy advances, average life expectancy in HIV-infected individuals on effective treatment is significantly decreased relative to uninfected persons, largely because of increased incidence of inflammation-related diseases, such as cardiovascular disease and renal dysfunction. The enteric microbial community could potentially cause this inflammation, as HIV-driven destruction of gastrointestinal CD4 T cells may disturb the microbiota-mucosal immune system balance, disrupting the stable gut microbiome and leading to further deleterious host outcomes...
February 2017: Current Opinion in Infectious Diseases
https://www.readbyqxmd.com/read/27917639/lack-of-effect-of-maraviroc-intensification-on-blood-and-gut-reservoir
#16
Juan Tiraboschi, Shuvra Ray, Kamal Patel, Matthew Pace, Prabhjeet Phalora, Nicola Robinson, Emily Hopkins, Jodi Meyerowitz, Yanzhong Wang, Olubanke Davies, Christine Mant, John Cason, Steve Kaye, Jeremy Sanderson, Sara Fidler, Paul Klenerman, John Frater, Julie Fox
We show that intensification of treatment with maraviroc in patients chronically infected with HIV-1 receiving successful long-term ART was not associated with improvements in HIV related morbidity, HIV reservoir, microbial translocation, immune activation or immune exhaustion in either gut or peripheral blood. The measurement of reservoir in both gut and blood longitudinally contributes to a paucity of data in the area.
December 4, 2016: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/27906073/gut-barrier-structure-mucosal-immunity-and-intestinal-microbiota-in-the-pathogenesis-and-treatment-of-hiv-infection
#17
REVIEW
Camilla Tincati, Daniel C Douek, Giulia Marchetti
Over the past 10 years, extensive work has been carried out in the field of microbial translocation in HIV infection, ranging from studies on its clinical significance to investigations on its pathogenic features. In the present work, we review the most recent findings on this phenomenon, focusing on the predictive role of microbial translocation in HIV-related morbidity and mortality, the mechanisms by which it arises and potential therapeutic approaches. From a clinical perspective, current work has shown that markers of microbial translocation may be useful in predicting clinical events in untreated HIV infection, while conflicting data exist on their role in cART-experienced subjects, possibly due to the inclusion of extremely varied patient populations in cohort studies...
April 11, 2016: AIDS Research and Therapy
https://www.readbyqxmd.com/read/27898686/gut-homing-cd4-and-cd8-t-cell-frequencies-in-hiv-infected-individuals-on-antiretroviral-treatment
#18
Olivia Briceño, Sandra Pinto-Cardoso, Nataly Rodríguez-Bernabe, Akio Murakami-Ogasawara, Gustavo Reyes-Terán
The depletion of mucosal CD4+ T-cells occurs early in HIV infection and despite years on antiretroviral treatment (ART), this population never reconstitutes to pre-HIV infection levels. In an effort to understand the effect of ART initiation and different ART regimens on the reconstitution of mucosal T cells within the gut associated lymphoid tissue (GALT), we quantified the frequency of CD4+ and CD8+ T cells expressing the gut homing receptors CCR9 and β7 in peripheral blood (PB) of HIV infected individuals naive to ART and treated individuals on both short-term (less than a year) and long-term ART (more than 2 years)...
2016: PloS One
https://www.readbyqxmd.com/read/27895171/impairment-of-ccr6-and-cxcr3-th-cell-migration-in-hiv-1-infection-is-rescued-by-modulating-actin-polymerization
#19
Valentina Cecchinato, Enos Bernasconi, Roberto F Speck, Michele Proietti, Ulrike Sauermann, Gianluca D'Agostino, Gabriela Danelon, Tanja Rezzonico Jost, Fabio Grassi, Lorenzo Raeli, Franziska Schöni-Affolter, Christiane Stahl-Hennig, Mariagrazia Uguccioni
CD4(+) T cell repopulation of the gut is rarely achieved in HIV-1-infected individuals who are receiving clinically effective antiretroviral therapy. Alterations in the integrity of the mucosal barrier have been indicated as a cause for chronic immune activation and disease progression. In this study, we present evidence that persistent immune activation causes impairment of lymphocytes to respond to chemotactic stimuli, thus preventing their trafficking from the blood stream to peripheral organs. CCR6(+) and CXCR3(+) Th cells accumulate in the blood of aviremic HIV-1-infected patients on long-term antiretroviral therapy, and their frequency in the circulation positively correlates to levels of soluble CD14 in plasma, a marker of chronic immune activation...
January 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27860212/alcohol-and-dietary-factors-associate-with-gut-integrity-and-inflammation-in-hiv-infected-adults
#20
A R Webel, A Sattar, N T Funderburg, B Kinley, C T Longenecker, D Labbato, Sm Khurshid Alam, G A McComsey
OBJECTIVES: HIV-infected adults have heightened monocyte activation and inflammation, at least partially as a consequence of altered gut integrity. The role of dietary factors in microbial translocation and inflammation and their downstream effect on markers of cardiovascular disease (CVD) have not been explored. Our purpose was to describe the longitudinal dietary patterns of HIV-infected adults, and to examine the relationship between dietary intake, gut integrity, inflammation and subclinical markers of CVD in HIV-infected adults...
November 9, 2016: HIV Medicine
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