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https://www.readbyqxmd.com/read/28198699/longitudinal-imaging-of-hiv-1-spread-in-humanized-mice-with-parallel-3d-immunofluorescence-and-electron-tomography
#1
Collin Kieffer, Mark S Ladinsky, Allen Ninh, Rachel P Galimidi, Pamela J Bjorkman
Dissemination of HIV-1 throughout lymphoid tissues leads to systemic virus spread following infection. We combined tissue clearing, 3D-immunofluorescence, and electron tomography (ET) to longitudinally assess early HIV-1 spread in lymphoid tissues in humanized mice. Immunofluorescence revealed peak infection density in gut at 10-12 days post-infection when blood viral loads were low. Human CD4+ T-cells and HIV-1-infected cells localized predominantly to crypts and the lower third of intestinal villi. Free virions and infected cells were not readily detectable by ET at 5-days post-infection, whereas HIV-1-infected cells surrounded by pools of free virions were present in ~10% of intestinal crypts by 10-12 days...
February 15, 2017: ELife
https://www.readbyqxmd.com/read/28196049/hiv-infection-in-the-native-and-allograft-kidney-implications-for-management-diagnosis-and-transplantation
#2
Véronique Avettand-Fenoël, Christine Rouzioux, Christophe Legendre, Guillaume Canaud
The native kidney is a reservoir for HIV-1 and a site of viral replication, similar to lymphoid tissue, gut-associated lymphoid tissue or semen. The ability of the virus to persist may result from either a true latency or sequestration in an anatomic site that is not effectively exposed to antiretroviral therapy. The presence of HIV in kidney epithelial cells will lead progressively to end-stage renal disease. For decades, HIV-infected patients were excluded from consideration for kidney transplantation. Hemodialysis and peritoneal dialysis were the only forms of treatment available to these patients...
February 11, 2017: Transplantation
https://www.readbyqxmd.com/read/28177967/the-neutralizing-and-targeting-properties-of-a-new-set-of-%C3%AE-4%C3%AE-7-specific-antibodies-are-influenced-by-their-isotype
#3
Alexandre Girard, Katija Jelicic, Don Van Ryk, Nicolas Rochereau, Claudia Cicala, James Arthos, Christian Genin, Bernard Verrier, Stephanie Laurant, Diane Razanajaoana-Doll, Pin Jean-Jacques, Stéphane Paul
The homing of lymphocytes to mucosa is mainly controlled by α4β7 integrin, and it is amplified during gut chronic inflammation, as occurs with HIV and/or Inflammatory Bowel Diseases. We designed and applied an improved immunization strategy based on an innovative selection process to isolate new α4β7 lymphocyte-specific mAbs that are able to prevent their migration into inflamed gut tissues and/or to counteract HIV infection in vitro. Firstly, five mAbs (one IgA, one IgM, and four IgGs) were selected based on their capacity to recognize α4 or β7 homodimers and α4β7 heterodimers in transfected human cells...
February 7, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28174773/dietary-fibre-based-scfa-mixtures-promote-both-protection-and-repair-of-intestinal-epithelial-barrier-function-in-a-caco-2-cell-model
#4
Tingting Chen, Choon Young Kim, Amandeep Kaur, Lisa Lamothe, Maliha Shaikh, Ali Keshavarzian, Bruce R Hamaker
Impaired gut barrier function plays an important role in the development of many diseases such as obesity, inflammatory bowel disease, and in HIV infection. Dietary fibres have been shown to improve intestinal barrier function through their fermentation products, short chain fatty acids (SCFAs), and the effects of individual SCFAs have been studied. Here, different SCFA mixtures representing possible compositions from fibre fermentation products were studied for protective and reparative effects on intestinal barrier function...
February 8, 2017: Food & Function
https://www.readbyqxmd.com/read/28128885/mechanisms-of-hiv-persistence-in-hiv-reservoirs
#5
REVIEW
Mayibongwe L Mzingwane, Caroline T Tiemessen
The establishment and maintenance of HIV reservoirs that lead to persistent viremia in patients on antiretroviral drugs remains the greatest challenge of the highly active antiretroviral therapy era. Cellular reservoirs include resting memory CD4+ T lymphocytes, implicated as the major HIV reservoir, having a half-life of approximately 44 months while this is less than 6 hours for HIV in plasma. In some individuals, persistent viremia consists of invariant HIV clones not detected in circulating resting CD4+ T lymphocytes suggesting other possible sources of residual viremia...
January 27, 2017: Reviews in Medical Virology
https://www.readbyqxmd.com/read/28128004/long-acting-slow-effective-release-antiretroviral-therapy
#6
Benson Edagwa, JoEllyn McMillan, Brady Sillman, Howard E Gendelman
Advances in long-acting antiretroviral therapy (ART) can revolutionize current HIV/AIDS treatments. We coined the term 'long-acting slow effective release ART' (LASER ART) to highlight the required formulation properties of slow drug dissolution, poor water-solubility, bioavailability, little-to-no off-target toxicities and improved regimen adherence. Drug carrier technologies characterized by high antiretroviral drug (ARV) payloads in a single carrier improve the pharmacokinetic and pharmacodynamic profiles...
February 6, 2017: Expert Opinion on Drug Delivery
https://www.readbyqxmd.com/read/28125732/dysregulation-of-systemic-and-mucosal-humoral-responses-to-microbial-and-food-antigens-as-a-factor-contributing-to-microbial-translocation-and-chronic-inflammation-in-hiv-1-infection
#7
Zdenek Hel, Jun Xu, Warren L Denning, E Scott Helton, Richard P H Huijbregts, Sonya L Heath, E Turner Overton, Benjamin S Christmann, Charles O Elson, Paul A Goepfert, Jiri Mestecky
HIV-1 infection is associated with an early and profound depletion of mucosal memory CD4+ T cells, a population that plays an indispensable role in the regulation of isotype switching and transepithelial transport of antibodies. In this study, we addressed whether the depletion of CD4+ T cell in HIV-1-infected individuals results in altered humoral responses specific to antigens encountered at mucosal surfaces. Comprehensive protein microarray of systemic humoral responses to intestinal microbiota demonstrated reduced IgG responses to antigens derived from Proteobacteria and Firmicutes but not Bacteroidetes...
January 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28118207/rectal-microbiota-among-hiv-uninfected-untreated-hiv-and-treated-hiv-infected-men-who-have-sex-with-men-msm-in-nigeria
#8
Rebecca G Nowak, Søren M Bentzen, Jacques Ravel, Trevor A Crowell, Wuese Dauda, Bing Ma, Hongjie Liu, William A Blattner, Stefan D Baral, Manhattan E Charurat
OBJECTIVE: Untreated advanced HIV infection alters the gut microbiota, but it is unclear whether antiretroviral therapy (ART) reverses these changes. We compared the composition of the rectal microbiota among three groups of men who have sex with men (MSM): HIV-uninfected, untreated HIV, and ART-treated HIV-infected. DESIGN: A cross-sectional study was conducted among 130 MSM (55 HIV-uninfected, 41 untreated HIV, 34 ART-treated HIV) in Abuja, Nigeria. METHODS: Bacterial 16S rRNA genes were amplified from rectal swabs, sequenced and clustered into Genera-level operational taxonomic units...
January 21, 2017: AIDS
https://www.readbyqxmd.com/read/28081037/higher-cd163-levels-are-associated-with-insulin-resistance-in-hepatitis-c-virus-infected-and-hiv-infected-adults
#9
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
#10
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
#11
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
#12
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
#13
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 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 microbial translocation 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 (BPB) species in colonic biopsies and stool of untreated, chronic HIV-1-infected (n = 18) and HIV-1-uninfected (n = 14) study participants...
February 20, 2017: AIDS
https://www.readbyqxmd.com/read/28000678/the-effects-of-prebiotics-on-microbial-dysbiosis-butyrate-production-and-immunity-in-hiv-infected-subjects
#14
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
#15
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
#16
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
#17
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
#18
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/toll-like-receptor-2-ligation-enhances-hiv-1-replication-in-activated-ccr6-cd4-t-cells-by-increasing-virus-entry-and-establishing-a-more-permissive-environment-to-infection
#19
Jean-François Bolduc, Michel Ouellet, Laurent Hany, Michel J Tremblay
: In this study, we investigated the effect of Toll-like receptor 2 (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 us to study the effect of TLR2 triggering on virus production at both population and single-cell levels...
February 15, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27926729/intracellular-allosteric-antagonism-of-the-ccr9-receptor
#20
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
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