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Archana Kulkarni, Swarali Kurle, Ashwini Shete, Manisha Ghate, Sheela Godbole, Vijaya Madhavi, Stephen J Kent, Ramesh Paranjape, Madhuri Thakar
HIV-specific antibody-dependent cell cytotoxicity (ADCC) is likely to be important in governing protection from human immunodeficiency virus (HIV) and slowing disease progression. Little is known about the ADCC responses to HIV-1 subtype C. We characterized ADCC responses in HIV-1 subtype C-infected Indian subjects with slow disease progression and identified the dominant antigenic regions recognized by these antibodies. ADCC responses were measured in plasma from 34 long-term non-progressors (LTNPs), who were asymptomatic and maintained CD4 count above 500 cells/mm(3) for the last 7 years in the absence of antiretroviral therapy (ART), and 58 ART naïve progressors with CD4 count <500 cells/mm(3) against overlapping HIV-1 peptides using a flow cytometry-based antibody-dependent natural killer (NK) cell activation assay...
2017: Frontiers in Immunology
B Dominguez-Molina, L Tarancon-Diez, S Hua, C Abad-Molina, E Rodriguez-Gallego, K Machmach, F Vidal, C Tural, S Moreno, J M Goñi, E Ramírez de Arellano, M Del Val, M F Gonzalez-Escribano, J Del Romero, C Rodriguez, L Capa, P Viciana, J Alcamí, X G Yu, B D Walker, Manuel Leal, M Lichterfeld, E Ruiz-Mateos
BACKGROUND: HIV-1-controllers maintain HIV-1 viremia at low levels (normally <2000 HIV-RNA copies/mL) without antiretroviral treatment. However, some HIV-1-controllers have evidence of immunologic progression with marked CD4(+)T-cell decline. We investigated host genetic factors associated with protection against CD4(+)T-cell loss in HIV-1-controllers. METHODS: We analysed the association of interferon lambda 4 (IFNL4)-related polymorphisms and HLA-B haplotypes within Long Term Non-Progressor HIV-1-controllers ((LTNP-C), defined by maintaining CD4(+)T-cells counts >500 cells/mm(3) for more than 7 years after HIV-1 diagnosis) versus non-LTNP-C, who developed CD4(+)T-cells counts <500 cells/mm(3) Both a Spanish study cohort (n=140) and an international validation cohort (n=914) were examined...
December 16, 2016: Clinical Infectious Diseases: An Official Publication of the Infectious Diseases Society of America
Yuanyuan Qiao, Lai Man, Zonglin Qiu, Lingli Yang, Youxiang Sun, Yuxian He
Isolation and characterization of novel HIV-1 neutralizing antibodies assists the development of effective AIDS vaccines and immune therapeutics. In this study, we constructed a phage display antibody library by using the PBMC samples of a clade B' HIV-1-infected long-term nonprogressor (LTNP) whose sera exhibited broadly neutralizing activity. A novel human monoclonal antibody (hMAb), termed A16, was identified by panning the library with two clades of HIV-1 Env glycoproteins. We demonstrated that A16 neutralized 32% of 73 tested HIV-1 isolates and it targeted the CD4-binding site (CD4bs) of gp120 with high affinity...
August 2016: Antiviral Research
Rakesh Dey, Kartik Soni, Shanmugam Saravanan, Pachamuthu Balakrishnan, Vikram Kumar, Jayaseelan Boobalan, Sunil Suhas Solomon, Vinod Scaria, Suniti Solomon, Samir K Brahmachari, Beena Pillai
HIV-1 replication inside host cells is known to be regulated by various host factors. Host miRNAs, by virtue of its normal functioning, also regulate HIV-1 RNA expression by either directly targeting virus mRNAs or indirectly by regulating host proteins that HIV-1 uses for own replication. Therefore, it is highly possible that with differential miRNA expression, rate of disease progression will vary in HIV-1 infected individuals. In this study we have compared expression of a panel of 13 reported anti-HIV miRNAs in human PBMCs from long term non progressors (LTNPs), regular progressors and rapid progressors...
2016: Scientific Reports
J Liu, P Y Fan, X J Xue, D Y Sun, G Q Sun, C H Liu, S A Tian, N Li, Q Zhu, Z Wang
OBJECTIVE: To study the prevalence and characteristics of long-term non-progressors (LTNPs) and HIV controllers (HCs) among HIV-infections in Henan, China. METHODS: Data in two databases (Information management system of HIV/AIDS prevention and control; HIV/AIDS testing application platform of Henan) were used to identify the LTNPs and HCs, investigation and verification, sample collection and correlation testing were carried out thereafter. RESULTS: A total of 148 LTNPs/HCs were identified...
February 2016: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
Surya Shrivastava, Jay Trivedi, Debashis Mitra
Human Immunodeficiency Virus-1 (HIV-1) encodes a 27 kDa Negative Factor or Nef protein, which is increasingly proving to be a misnomer. Nef seems to be crucial for AIDS progression as individuals infected with nef-deleted strain of HIV were reported to become Long Term Non Progressors (LTNP). These findings necessitate tracing of Nef's footprint on landscape of cellular transcriptome favoring HIV-1 pathogenesis. We have tried to explore effect of Nef on cellular gene expression profile in conjunction with rest of HIV-1 proteins...
March 25, 2016: Biochemical and Biophysical Research Communications
C D Eckstrand, C Hillman, A L Smith, E E Sparger, B G Murphy
BACKGROUND: Examination of a cohort of cats experimentally infected with feline immunodeficiency virus (FIV) for 5.75 years revealed detectable proviral DNA in peripheral blood mononuclear cells (PBMCs) harvested during the asymptomatic phase, undetectable plasma viral RNA (FIV gag), and rarely detectable cell-associated viral RNA. Despite apparent viral latency in peripheral CD4+ T cells, circulating CD4+ T cell numbers progressively declined in progressor animals. The aim of this study was to explore this dichotomy of peripheral blood viral latency in the face of progressive immunopathology...
2016: PloS One
Uday A Phatak, P V Chitale, Rakhi V Jagdale
Long-term non-progressor HIV infection (LTNP-HIV) is seen in <1 percent of HIV-afflicted population. There are definite criteria for the diagnosis of LTNP-HIV. Malignancies either solid tumors or haematological cancers have not been reported in such population. We report here a rare case of follicular thyroid carcinoma in LTNP-HIV infection. She never had any opportunistic infections. She did not receive anti-retroviral therapy in the entire course of illness and continued to have good quality of life. Treatment of follicular thyroid cancer was similar to other patients without HIV infection...
July 2015: Indian Journal of Sexually Transmitted Diseases
Xin Sun, Wei Li, Wenzhen Liu, Rui Wang, Qunhui Li, Hao Wu
BACKGROUND: The tripartite interaction motif 5a (Trim5a) plays critical roles in restricting various kinds of retroviruses in different species. It has been shown that Trim5a could inhibit HIV-1 inhibition in vitro. METHODS: In this study, 16 SNPs of Trim5a gene were screened in 236 acutely HIV-infected patients (169 common type (CT) patients and 67 patients with rapid disease progression). In addition, they were screened in 162 chronically HIV-infected patients (147 common type patients and 15 long-term non-progressors (LTNP))...
2015: International Journal of Clinical and Experimental Medicine
Maria Pernas, Victor Sanchez-Merino, Concepcion Casado, Alberto Merino-Mansilla, Isabel Olivares, Eloisa Yuste, Cecilio Lopez-Galindez
This study evaluated the neutralization breadth in dually infected (DI) HIV-1 long-term non-progressor elite controller patients (LTNP-EC) using a representative minipanel of 6 viruses from 5 different subtypes. Our results showed an improved neutralization breadth in DI LTNP-EC patients when compared with matched LTNP single-infected patients. The role of viral diversity in neutralization was estimated with the Shannon Entropy and the p-distance in viral quasispecies. We found a positive correlation between neutralization breadth and diversity within the viral quasispecies...
2015: PloS One
Stephen A Migueles, Daniel Mendoza, Matthew G Zimmerman, Kelly M Martins, Sushila A Toulmin, Elizabeth P Kelly, Bennett A Peterson, Sarah A Johnson, Eric Galson, Kate O Poropatich, Andy Patamawenu, Hiromi Imamichi, Alexander Ober, Catherine A Rehm, Sara Jones, Claire W Hallahan, Dean A Follmann, Mark Connors
Understanding natural immunologic control over Human Immunodeficiency Virus (HIV)-1 replication, as occurs in rare long-term nonprogressors/elite controllers (LTNP/EC), should inform the design of efficacious HIV vaccines and immunotherapies. Durable control in LTNP/EC is likely mediated by highly functional virus-specific CD8(+) T-cells. Protective Human Leukocyte Antigen (HLA) class I alleles, like B*27 and B*57, are present in most, but not all LTNP/EC, providing an opportunity to investigate features shared by their HIV-specific immune responses...
January 2015: EBioMedicine
Yuxia Hao, Ge Bai, Junping Wang, Longfeng Zhao, Kyle Sutherland, Jianfeng Cai, Chuanhai Cao
BACKGROUND: HIV-infected long-term non-progressor (LTNP) subjects can prevent viral replication and may harbor useful information for the development of both antibody and active vaccination treatments. In this study we used LTNP sera to examine the epitopes presented to the gp160 protein, and from this procedure we hope to elucidate potential biomarkers pertaining to the level of resistance a patient may have in developing AIDS after infection with HIV. We used five clinical sera samples from LTNP patients to identify common epitopes by ELISA; peptides with high binding to sera were selected and analyzed for conservation among HIV clades...
2015: BMC Immunology
C Morén, M Bañó, I González-Casacuberta, M Catalán-Garcia, M Guitart-Mampel, E Tobías, F Cardellach, E Pedrol, J Peraire, F Vidal, P Domingo, Ò Miró, J M Gatell, E Martínez, G Garrabou
OBJECTIVES: Ex vivo analysis of mitochondrial function may reveal HIV progression and the impact of ART. We propose a mitochondrial and apoptotic in vitro model using Jurkat T cells incubated with plasma. The objectives of this study were to evaluate mitochondrial and apoptotic lesions in this model in relation to HIV progression, and to assess the effect of >1 year of standard non-thymidine-containing therapy. METHODS: This was a cross-sectional comparison among three age- and gender-matched groups (n = 19 × 3): healthy non-HIV-infected participants, HIV-infected long-term non-progressors (LTNPs) and standard antiretroviral-naive chronically infected patients [standard progressors (Sps)], longitudinally evaluated before (Sp1) and after (Sp2) >1 year of efavirenz + tenofovir + emtricitabine therapy...
August 2015: Journal of Antimicrobial Chemotherapy
Daisuke Sakurai, Yasumasa Iwatani, Hitoshi Ohtani, Taeko K Naruse, Hiroshi Terunuma, Wataru Sugiura, Akinori Kimura
Human APOBEC3H (A3H) is a member of APOBEC3 cytidine deaminase family that potently restricts HIV-1 replication. Because A3H is genetically divergent with different intracellular stability and anti-HIV-1 activity in vitro, we investigated a possible association of A3H with susceptibility to HIV-1 infection and disease progression in Japanese populations. A total of 191 HIV-1-infected individuals (HIV group), 93 long-term non-progressors to AIDS (LTNP group) and 421 healthy controls were genotyped for two functional APOBEC3H polymorphisms, rs139292 and rs139297...
April 2015: Immunogenetics
Hinta Meijerink, Agnes R Indrati, Reinout van Crevel, Irma Joosten, Hans Koenen, Andre J A M van der Ven
BACKGROUND: The HIV co-receptors CXCR4 and CCR5 play an important role in HIV infection and replication. Therefore we hypothesize that long-term non-progressors (LTNP) with viral control have lower expression of CCR5 and CXCR4 on CD4(+) cells, specifically on memory T-lymphocytes since they are the primary target cells of HIV. METHODS: In this cross-sectional study, we included five HIV-infected LTNP with viral control (CD4 > 750 cell/μl & HIV < 50 copies for ≥2 years), thirteen HIV-infected and seven HIV-uninfected individuals at Radboud UMC Nijmegen, the Netherlands...
2014: BMC Infectious Diseases
Shokouh Makvandi-Nejad, Sarah Rowland-Jones
A substantial proportion of people infected with HIV-2, the second causative agent of acquired immune deficiency syndrome (AIDS), behave as long-term non-progressors (LTNP) and are able to control the infection more effectively than most HIV-1-infected patients. A better understanding of the differences in the natural history of HIV-1 and HIV-2 infection, and how these relate to the relative immunogenicity and evolution of the two virus strains, could provide important insights into the mechanisms of protective immunity in HIV infection...
January 2015: Immunology Letters
Xiujuan Xue, Guoqing Sun, Chunhua Liu, Jia Liu, Suian Tian, Zhe Wang
OBJECTIVE: To explore the related testing indicators variation of HIV long-term non-progress populations. METHODS: The long-term non-progress populations in some areas of Henan were recruited, and the study was carried out according to different CD4(+)T lymphocytes counts for two groups. The dynamic characteristics of immune status and viral load between LTNP-1group (CD4(+)T lymphocytes ≥ 500/µl, 42 cases) and LTNP-2 group(350/µl ≤ CD4(+)T lymphocytes < 500/µl, 49 cases) from July 2010 to August 2013 were observed...
August 2014: Zhonghua Yu Fang Yi Xue za Zhi [Chinese Journal of Preventive Medicine]
B H Rimawi, R H Rimawi, M Micallef, L Pinckney, S L Fowler, T C Dixon
Patients infected with HIV are best categorized along a continuum from rapid progressors to HIV long-term nonprogressors. Long-term nonprogressors (LTNPs) are those in which AIDS develop many years after being infected with HIV, often beyond the 10-year mark, and represent 15-20% of the HIV infected patients. Many of these patients are able to control their infection and maintain undetectable viral loads for long periods of time without antiretroviral therapy. After a comprehensive literature search, we found extensive data related to HIV LTNPs in the adult population; however, very limited data was available related to LTNPs within the pediatric population...
2014: Case Reports in Infectious Diseases
Caroline Pereira Bittencourt Passaes, Cynthia Chester Cardoso, Diogo Gama Caetano, Sylvia Lopes Maia Teixeira, Monick Lindenmeyer Guimarães, Dayse Pereira Campos, Valdilea Gonçalves Veloso, Dunja Z Babic, Mario Stevenson, Milton Ozório Moraes, Mariza Gonçalves Morgado
The lens epithelium-derived growth factor p75 (LEDGF/p75), coded by the PSIP1 gene, is an important host co-factor that interacts with HIV-1 integrase to target integration of viral cDNA into active genes. The aim of this study was to investigate the association of SNPs in the PSIP1 gene with disease outcome in HIV-1 infected patients. We performed a genetic association study in a cohort of 171 HIV-1 seropositive Brazilian individuals classified as rapid progressors (RP, n = 69), typical progressors (TP, n = 79) and long-term nonprogressors (LTNP, n = 23)...
2014: PloS One
Maria Carolina Luque, Camila C Santos, Eliane C Mairena, Peter Wilkinson, Genèvieve Boucher, Aluisio C Segurado, Luiz A Fonseca, Ester Sabino, Jorge E Kalil, Edecio Cunha-Neto
Long-term non-progressors (LTNP) represent a minority (1-5%) of HIV-infected individuals characterized by documented infection for more than 7-10 years, a stable CD4+ T cell count over 500/mm(3) and low viremia in the absence of antiretroviral treatment. Protective factors described so far such as the CCR5delta32 deletion, protective HLA alleles, or defective viruses fail to fully explain the partial protection phenotype. The existence of additional host resistance mechanisms in LTNP patients was investigated here using a whole human genome microarray study comparing gene expression profiles of unstimulated peripheral blood mononuclear cells from LTNP patients, HIV-1 infected patients under antiretroviral therapy with CD4+ T cell levels above 500/mm(3) (ST), as well as healthy individuals...
November 2014: Molecular Immunology
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