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Hiv inflammation

Hui Liu, Frank Gambino, Crystal Algenio, Charles Bouchard, Liang Qiao, Ping Bu, Shaozhen Zhao
Dry Eye Disease (DED) is a very common disorder that can result in severe disability and vision loss. Although the pathogenesis of DED is not fully understood, hyperosmolarity, inflammation, and tear film instability are recognized as hallmarks of DED. Recently, Nucleoside Reverse Transcriptase Inhibitors (NRTIs), a class of medication used to treat HIV, have been shown to inhibit inflammation in a mouse model of retinal atrophy. In this study, we investigated whether Zidovudine (AZT) can inhibit human corneal epithelial cell (HCEC) inflammatory responses under hyperosmotic conditions...
March 16, 2018: Biochemical and Biophysical Research Communications
Annesa Flentje, Kord Kober, Adam Carrico, Torsten B Neilands, Elena Flowers, Nicholas Heck, Bradley Aouizerat
Sexual minority (i.e., non-heterosexual) individuals experience poorer mental and physical health, accounted for in part by the additional burden of sexual minority stress occurring from being situated in a culture favoring heteronormativity. Informed by previous research, the purpose of this study was to identify the relationship between sexual minority stress and leukocyte gene expression related to inflammation, cancer, immune function, and cardiovascular function. Sexual minority men living with HIV who were on anti-retroviral medication, had viral load <200 copies/mL, and had biologically confirmed, recent methamphetamine use completed minority stress measures and submitted blood samples for RNA sequencing on leukocytes...
March 13, 2018: Brain, Behavior, and Immunity
Yufei Chen, Yannick L Traore, Sidi Yang, Julie Lajoie, Keith R Fowke, Daniel W Rickey, Emmanuel A Ho
Evidence suggests that women who are naturally resistant to HIV infection exhibit low baseline immune activation at the female genital tract (FGT). This "immune quiescent" state is associated with lower expression of T-cell activation markers, reduced levels of gene transcription and pro-inflammatory cytokine or chemokine production involved in HIV infection while maintaining an intact immune response against pathogens. Therefore, if this unique immune quiescent state can be pharmacologically induced locally, it will provide an excellent women-oriented strategy against HIV infection To our knowledge, this is the first research article evaluating in vivo, an innovative trackable implant that can provide controlled delivery of hydroxychloroquine (HCQ) to successfully attenuate vaginal T lymphocyte activation and inflammation in a rabbit model as a potential strategy to induce an "immune quiescent" state within the FGT for the prevention of HIV infection...
March 12, 2018: Journal of Controlled Release: Official Journal of the Controlled Release Society
Rose Nabatanzi, Stephen Cose, Moses Joloba, Sarah Rowland Jones, Damalie Nakanjako
HIV infection causes upregulation of markers of inflammation, immune activation and apoptosis of host adaptive, and innate immune cells particularly monocytes, natural killer (NK) and innate lymphoid cells (ILCs). Although antiretroviral therapy (ART) restores CD4 T-cell counts, the persistent aberrant activation of monocytes, NK and ILCs observed likely contributes to the incomplete recovery of T-cell effector functions. A better understanding of the effects of HIV infection and ART on the phenotype and function of circulating monocytes, NK, and ILCs is required to guide development of novel therapeutic interventions to optimize immune recovery...
March 15, 2018: AIDS Research and Therapy
Beiqing Wu, Jianhui Liu, Runze Zhao, Yuju Li, Justin Peer, Alexander L Braun, Lixia Zhao, Yi Wang, Zenghan Tong, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release...
March 14, 2018: Journal of Neuroinflammation
Xia Jin, Hua Xu, Michael S McGrath
Monocyte activation and polarization play essential roles in many chronic inflammatory diseases. An imbalance of M1 and M2 macrophage activation (pro-inflammatory and alternatively activated, respectively) is believed to be a key aspect in the etiology of these diseases, thus a therapeutic approach that regulates macrophage activation could be of broad clinical relevance. Methylglyoxal-bis-guanylhydrazone (MGBG), a regulator of polyamine metabolism, has recently been shown to be concentrated in monocytes and macrophages, and interfere with HIV integration into the DNA of these cells in vitro...
2018: PloS One
Mimi Ghosh, Mariel Jais, Roshni Biswas, Jason Jarin, Jason Daniels, Christopher Joy, Monika Juzumaite, Vanessa Emmanuel, Veronica Gomez-Lobo
PROBLEM: Adolescent girls are disproportionately affected by the HIV/AIDS pandemic, accounting for 22% of all new HIV infections globally. Yet little is known regarding the immune microenvironment of the adolescent female reproductive tract, especially regarding differences among sexually active and inactive girls, a critical parameter to evaluate HIV susceptibility associated with young age and sexual debut. METHODS: Cervico-vaginal lavage (CVL) was collected from sexually active (10) and inactive (8) girls aged 11-19 years and analyzed by ELISA for inflammation-associated biomarkers IL-6, IL-8, TNF-α, MIP-3α, IL-1α, IL-1β, matrix metalloproteinases (MMP) 1, 2, 7, 8, and 9, as well as anti-HIV mediators, Elafin, SLPI, human beta-defensin 2, and tissue inhibitor of matrix metalloproteinases (TIMP) 1 and 2...
March 13, 2018: American Journal of Reproductive Immunology: AJRI
Joseph B Margolick, Jay H Bream, Tricia L Nilles, Huifen Li, Susan J Langan, Shane Deng, Ruibin Wang, Nikolas Wada, Sean X Leng
Background: Both aging and treated human immunodeficiency virus (HIV)-infected populations exhibit low-level chronic immune activation of unknown etiology, which correlates with morbidity and mortality. Cytomegalovirus (CMV) infection is common in both populations, but its relation to immune activation is unknown. Methods: T cells from men who have sex with men (22 virologically suppressed HIV+, 20 HIV-) were stimulated with peptides spanning 19 CMV open reading frames, and intracellular cytokine responses were assessed...
February 26, 2018: Journal of Infectious Diseases
Monica Gandhi, Rajesh T Gandhi, Andrei Stefanescu, Ronald J Bosch, Joshua C Cyktor, Howard Horng, Alexander Louie, Nhi Phung, Joseph J Eron, Evelyn Hogg, Bernard J C Macatangay, Christopher Hensel, Courtney V Fletcher, John W Mellors, Deborah K McMahon
Data on the relationship of antiretroviral exposure to measures of human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic measures were analyzed from individuals with sustained virologic suppression on therapy (median 7 years) in the AIDS Clinical Trials Group A5321 cohort. Among 110 participants on tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair concentrations of individual antiretrovirals (ARVs) in the regimen and measures of HIV persistence (plasma HIV-1 RNA by single copy assay, cell-associated-DNA, cell-associated RNA) or soluble markers of inflammation...
February 26, 2018: Journal of Infectious Diseases
John Joseph Heath, Neva Jennifer Fudge, Maureen Elizabeth Gallant, Michael David Grant
Antiretroviral therapy (ART) effectively extends the life expectancy of human immunodeficiency virus (HIV)-infected individuals; however, age-related morbidities have emerged as major clinical concerns. In this context, coinfection with cytomegalovirus (CMV) accelerates immune senescence and elevates risk for other age-related morbidities, possibly through increased inflammation. We investigated potential relationships between CMV memory inflation, immune senescence, and inflammation by measuring markers of inflammation and telomere lengths of different lymphocyte subsets in HIV-infected individuals seropositive for anti-CMV antibodies...
2018: Frontiers in Immunology
Daniel Sauter, Frank Kirchhoff
HIV-1, the main causative agent of AIDS, and related primate lentiviruses show a striking ability to efficiently replicate throughout the lifetime of an infected host. In addition to their high variability, the acquisition of several accessory genes has enabled these viruses to efficiently evade or counteract seemingly strong antiviral immune responses. The respective viral proteins, i.e. Vif, Vpr, Vpu, Vpx and Nef, show a stunning functional diversity, acting by various mechanisms and targeting a large variety of cellular factors involved in innate and adaptive immunity...
February 23, 2018: Cytokine & Growth Factor Reviews
Xiaoyan Pan, Jian Lin, Xiaoyun Zeng, Wenjuan Li, Wenjiao Wu, Wan Zhen Lu, Jing Liu, Shuwen Liu
The persistent inflammation aggravated by a disordered immune response is considered to be the major cause of CD4+ T cell depletion in lymphoid tissue, which impels the progression of AIDS. Here, we report that heat shock factor 1 (HSF1) works as an innate repressor of HIV-induced inflammation. The activation of HSF1 was found to accompany inflammation during HIV infection. Further research uncovered that HSF1 activation inhibited HIV-induced inflammation. In addition, HSF1 overexpression suppressed the inflammatory response induced by HIV, while HSF1 deficiency exacerbated that inflammation...
January 31, 2018: Cellular Immunology
Saverio G Parisi, Samantha Andreis, Carlo Mengoli, Nicola Menegotto, Silvia Cavinato, Renzo Scaggiante, Massimo Andreoni, Giorgio Palù, Monica Basso, Anna Maria Cattelan
Soluble CD163, soluble CD14 and cellular HIV-1-DNA levels reflect two different aspects of HIV infection: immune activation and the reservoir of infected cells. The aim of this study was to describe their relationships in a cohort of HIV-HCV co-infected patients successfully treated for both HCV and HIV infections. Fifty-five patients were recruited and studied prior to the start of direct-acting antivirals (DAAs) (T0), at week 12 of DAA treatment (T1) and 24 weeks after T0 (T2). The subjects were classified as having undetectable plasma HIV viraemia (UV) or low-level viraemia (LLV) in the 18 months before T2...
March 9, 2018: Medical Microbiology and Immunology
Mara Farcasanu, Douglas S Kwon
PURPOSE OF REVIEW: Young women in sub-Saharan Africa bear a disproportionate burden of the global HIV epidemic. In this review, we examine how cervicovaginal microbiota modulate structural and immune defenses in the female genital tract and influence HIV susceptibility. RECENT FINDINGS: Highly diverse, anaerobic cervicovaginal microbiota prevalent in sub-Saharan African women increase HIV acquisition risk by over fourfold. These bacteria weaken the barrier properties of the vaginal mucosa and increase local inflammation and HIV target cell recruitment, creating an environment permissive to HIV...
March 8, 2018: Current HIV/AIDS Reports
Vinay Kumar, Joshua Mansfield, Rong Fan, Andrew MacLean, Jian Li, Mahesh Mohan
Intestinal epithelial barrier dysfunction is a well-known sequela of HIV/SIV infection that persists despite antiretroviral therapy. Although inflammation is a triggering factor, the underlying molecular mechanisms remain unknown. Emerging evidence suggests that epithelial barrier function is epigenetically regulated by inflammation-induced microRNAs (miRNAs). Accordingly, we profiled and characterized miRNA/mRNA expression exclusively in colonic epithelium and identified 46 differentially expressed miRNAs (20 upregulated and 26 downregulated) in chronically SIV-infected rhesus macaques ( Macaca mulatta )...
March 7, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Abraham Siika, Leanne McCabe, Mutsa Bwakura-Dangarembizi, Cissy Kityo, Jane Mallewa, Jay Berkley, Kath Maitland, Anna Griffiths, Keith Baleeta, Shepherd Mudzingwa, James Abach, Kusum Nathoo, Margaret J Thomason, Andrew J Prendergast, Ann Sarah Walker, Diana M Gibb
Background: Severely immunocompromised human immunodeficiency virus (HIV)-infected individuals have high mortality shortly after starting antiretroviral therapy (ART). We investigated predictors of early mortality and "late presenter" phenotypes. Methods: The Reduction of EArly MortaLITY (REALITY) trial enrolled ART-naive adults and children ≥5 years of age with CD4 counts <100 cells/µL initiating ART in Uganda, Zimbabwe, Malawi, and Kenya. Baseline predictors of mortality through 48 weeks were identified using Cox regression with backwards elimination (exit P > ...
March 4, 2018: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Alexander J Gill, Rolando Garza, Surendra S Ambegaokar, Benjamin B Gelman, Dennis L Kolson
BACKGROUND: Heme oxygenase-1 (HO-1) is a critical cytoprotective enzyme that limits oxidative stress, inflammation, and cellular injury within the central nervous system (CNS) and other tissues. We previously demonstrated that HO-1 protein expression is decreased within the brains of HIV+ subjects and that this HO-1 reduction correlates with CNS immune activation and neurocognitive dysfunction. To define a potential CNS protective role for HO-1 against HIV, we analyzed a well-characterized HIV autopsy cohort for two common HO-1 promoter region polymorphisms that are implicated in regulating HO-1 promoter transcriptional activity, a (GT)n dinucleotide repeat polymorphism and a single nucleotide polymorphism (A(-413)T)...
March 6, 2018: Journal of Neuroinflammation
Yayun Chen, Fan Meng, Bingyu Wang, Liangmei He, Yangbin Liu, Zhiping Liu
An atypical guanine exchange factor, Dock2 is specifically expressed in hematopoietic cells and regulates activation and migration of immune cells through activating Ras-related C3 botulinum toxin substrate (Rac). Dock2 was shown to be critical in the development of various inflammatory diseases, including allergic diseases, HIV infection, and graft rejection in organ transplantation. DOCK2 mutation in infants was recently identified to be associated with T and B cell combined immunodeficiency. Furthermore, Dock2 is involved in host protection during enteric bacterial infection and is also associated with the proliferation of cancer cells...
March 6, 2018: European Journal of Immunology
Abbas Agaimy, Sarina K Mueller, Thomas Harrer, Sebastian Bauer, Lester D R Thompson
Kaposi sarcoma (KS) of the head and neck area is uncommon with limited published case series. Our routine and consultation files were reviewed for histologically and immunohistochemically proven KS affecting any cutaneous or mucosal head and neck site. Ten males and one female aged 42-78 years (median, 51 years; mean, 52 years) were retrieved. Eight patients were HIV-positive and three were HIV-negative. The affected sites were skin (n = 5), oral/oropharyngeal mucosa (n = 5), and lymph nodes (n = 3) in variable combination...
March 5, 2018: Head and Neck Pathology
Mohammad Arif Rahman, Katherine M McKinnon, Tatiana S Karpova, David A Ball, David J Venzon, Wenjin Fan, Guobin Kang, Qingsheng Li, Marjorie Robert-Guroff
Follicular CD8+ T (fCD8) cells reside within B cell follicles and are thought to be immune-privileged sites of HIV/SIV infection. We have observed comparable levels of fCD8 cells between chronically SIV-infected rhesus macaques with low viral loads (LVL) and high viral loads (HVL), raising the question concerning their contribution to viremia control. In this study, we sought to clarify the role of SIV-specific fCD8 cells in lymph nodes during the course of SIV infection in rhesus macaques. We observed that fCD8 cells, T follicular helper (Tfh) cells, and T follicular regulatory cells (Tfreg) were all elevated in chronic SIV infection...
March 5, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
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