scholarly journals Studies on the potential use of CD38 expression as a marker for the efficacy of anti-retroviral therapy in HIV-1-infected patients in Thailand

Virology ◽  
2005 ◽  
Vol 341 (2) ◽  
pp. 238-247 ◽  
Author(s):  
Nattawat Onlamoon ◽  
Sutchana Tabprasit ◽  
Surapol Suwanagool ◽  
Suda Louisirirotchanakul ◽  
Aftab A. Ansari ◽  
...  
Keyword(s):  
Cd38 Expression ◽  
Potential Use ◽  
Hiv 1

Expression of functional HIV-1 integrase in the yeastSaccharomyces cerevisiae leads to the emergence of a lethal phenotype: potential use for inhibitor screening

1996 ◽  
Vol 29 (6) ◽  
pp. 503-510 ◽  
Author(s):  
Anne B. Caumont ◽  
Gordon A. Jamieson ◽  
Sergio Pichuantes ◽  
Anton Tien Nguyen ◽  
Simon Litvak ◽  
...  
Keyword(s):  
Inhibitor Screening ◽  
Lethal Phenotype ◽  
Potential Use ◽  
Hiv 1

scholarly journals Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection

2008 ◽  
Vol 205 (12) ◽  
pp. 2763-2779 ◽  
Author(s):  
R. Brad Jones ◽  
Lishomwa C. Ndhlovu ◽  
Jason D. Barbour ◽  
Prameet M. Sheth ◽  
Aashish R. Jha ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Surface Expression ◽  
Cell Dysfunction ◽  
Cd38 Expression ◽  
Immunodeficiency Virus ◽  
T Cell Dysfunction ◽  
Novel Target ◽  
Hiv 1

Progressive loss of T cell functionality is a hallmark of chronic infection with human immunodeficiency virus 1 (HIV-1). We have identified a novel population of dysfunctional T cells marked by surface expression of the glycoprotein Tim-3. The frequency of this population was increased in HIV-1–infected individuals to a mean of 49.4 ± SD 12.9% of CD8+ T cells expressing Tim-3 in HIV-1–infected chronic progressors versus 28.5 ± 6.8% in HIV-1–uninfected individuals. Levels of Tim-3 expression on T cells from HIV-1–infected inviduals correlated positively with HIV-1 viral load and CD38 expression and inversely with CD4+ T cell count. In progressive HIV-1 infection, Tim-3 expression was up-regulated on HIV-1–specific CD8+ T cells. Tim-3–expressing T cells failed to produce cytokine or proliferate in response to antigen and exhibited impaired Stat5, Erk1/2, and p38 signaling. Blocking the Tim-3 signaling pathway restored proliferation and enhanced cytokine production in HIV-1–specific T cells. Thus, Tim-3 represents a novel target for the therapeutic reversal of HIV-1–associated T cell dysfunction.

Expression of functional HIV-1 integrase in the yeast Saccharomyces cerevisiae leads to the emergence of a lethal phenotype: potential use for inhibitor screening

1996 ◽  
Vol 29 (6) ◽  
pp. 503-510 ◽  
Author(s):  
Anne B. Caumont ◽  
Gordon A. Jamieson ◽  
Sergio Pichuantes ◽  
Anton Tien Nguyen ◽  
Simon Litvak ◽  
...  
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Yeast Saccharomyces Cerevisiae ◽  
Inhibitor Screening ◽  
Lethal Phenotype ◽  
Potential Use ◽  
Hiv 1

scholarly journals Neutralization Diversity of HIV-1 Indian Subtype C Envelopes Obtained From Cross Sectional and Followed up Individuals Against Broadly Neutralizing Monoclonal Antibodies Having Distinct Gp120 Specificities

2021 ◽  
Author(s):  
Ranajoy Mullick ◽  
Jyoti Sutar ◽  
Nitin Hingankar ◽  
Suprit Deshpande ◽  
Madhuri Thakar ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Additive Model ◽  
Clinical Development ◽  
Intervention Strategies ◽  
Subtype C ◽  
Cross Sectional ◽  
Clade C ◽  
Potential Use ◽  
Hiv 1 ◽  
Comprehensive Study

Abstract Background. The potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype C envs obtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.25, PGDM1400 and PGT121. Results. We found significant variations in the susceptibility of Indian clade C to these four bnAbs and were found to be distinct to that observed with that of African subtype C based on the existing datasets and were also found to be concordant with their sequence diversity. Trend analysis indicated an increasing neutralization resistance observed overtime with CAP25-VRC26.25, PGDM1400 and PGT121 when tested on pseudoviruses expressing envs obtained from 1999-2016. Our data was found to be distinct from what was observed in case of African HIV-1 subtype C. However, inconsistent trend in neutralization susceptibility was observed, when pseudoviruses expressing envs obtained from three followed up individuals were examined. Finally, through predictive analysis of the 98 Indian subtype C including those assessed in the present study by employing additive model implemented in CombiNAber (www.hiv.lanl.gov), we observed two possibilities where combinations of three bnAbs (VRC01/CAP56-VRC26.25/PGT121 and PGDM1400/CAP256-VRC26.25/PGT121) could achieve near 100% neutralization coverage. Conclusions. Our findings not only indicate disparate intra-clade C genetic vis-à-vis neutralization diversities but also warrants the need for more comprehensive study using additional isolates towards comparing inter and intra-clade neutralization diversities which will be necessary for selecting the bnAb combinations suitable for optimal coverage of the region-specific HIV-1 circulating subtypes. Expanding these efforts is imperative for designing efficacious bnAb based intervention strategies for India as well as subtype C in general.

scholarly journals Neutralization diversity of HIV-1 Indian subtype C envelopes obtained from cross sectional and followed up individuals against broadly neutralizing monoclonal antibodies having distinct gp120 specificities

Retrovirology ◽  
2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Ranajoy Mullick ◽  
Jyoti Sutar ◽  
Nitin Hingankar ◽  
Suprit Deshpande ◽  
Madhuri Thakar ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Additive Model ◽  
Clinical Development ◽  
Intervention Strategies ◽  
Subtype C ◽  
Cross Sectional ◽  
Clade C ◽  
Potential Use ◽  
Hiv 1 ◽  
Comprehensive Study

Abstract Background The potential use of the broadly neutralizing monoclonal antibodies (bnAbs) towards prophylaxis and treatment to HIV-1 is currently being explored. While a number of promising bnAbs have been discovered and a few of them have progressed towards clinical development, their extent of neutralization coverage with respect to global HIV-1 variants given the existence of genetically distinct subtypes and recombinants circulating globally is not clearly known. In the present study, we examined the variation in the neutralization susceptibility of pseudoviruses expressing 71 full length primary HIV-1 subtype C envs obtained from limited cross-sectional individuals over different time points against four bnAbs that target gp120 with distinct specificities: VRC01, CAP256-VRC26.25, PGDM1400 and PGT121. Results We found significant variations in the susceptibility of Indian clade C to these four bnAbs. These variations were found to be distinct to that observed in African subtype C based on the existing datasets and concordant with their sequence diversity. Trend analysis indicated an increasing neutralization resistance observed over time with CAP25-VRC26.25, PGDM1400 and PGT121 when tested on pseudoviruses expressing envs obtained from 1999 to 2016. However, inconsistent trend in neutralization susceptibility was observed, when pseudoviruses expressing envs obtained from three followed up individuals were examined. Finally, through predictive analysis of the 98 Indian subtype C including those assessed in the present study by employing additive model implemented in CombiNAber (http://www.hiv.lanl.gov), we observed two possibilities where combinations of three bnAbs (VRC01/CAP56-VRC26.25/PGT121 and PGDM1400/CAP256-VRC26.25/PGT121) could achieve near 100% neutralization coverage. Conclusions Our findings not only indicate disparate intra-clade C genetic vis-à-vis neutralization diversities but also warrant the need for more comprehensive study using additional isolates towards comparing inter and intra-clade neutralization diversities which will be necessary for selecting the bnAb combinations suitable for optimal coverage of the region-specific HIV-1 circulating subtypes. Expanding these efforts is imperative for designing efficacious bnAb based intervention strategies for India as well as subtype C in general.

scholarly journals Nonradioactive Techniques for Measurement of In Vitro T-Cell Proliferation: Alternatives to the [3H]Thymidine Incorporation Assay

2000 ◽  
Vol 7 (4) ◽  
pp. 687-692 ◽  
Author(s):  
Tsehaynesh Messele ◽  
Marijke T. L. Roos ◽  
Dorte Hamann ◽  
Maarten Koot ◽  
Arnaud L. Fontanet ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
T Cells ◽  
T Cell ◽  
Alternative Methods ◽  
Brdu Incorporation ◽  
T Cell Proliferation ◽  
Proliferative Capacity ◽  
Cd38 Expression ◽  
Hiv 1

ABSTRACT T-cell proliferation is an important in vitro parameter of in vivo immune function and has been used as a prognostic marker of human immunodeficiency virus type 1 (HIV-1) disease progression. The proliferative capacity of T cells in response to various stimuli is commonly determined by a radioactive assay based on incorporation of [3H]thymidine ([3H]TdR) into newly generated DNA. In order to assess techniques for application in laboratories where radioactive facilities are not present, two alternative methods were tested and compared to the [3H]TdR assay as a “gold standard.” As an alternative, T-cell proliferation was measured by flow cytometric assessment of CD38 expression on T cells and by an enzyme-linked immunosorbent assay (ELISA) based on bromo-2′-deoxyuridine (BrdU) incorporation. Peripheral blood mononuclear cells (PBMCs), either in whole blood or Ficoll-Isopaque separated, from a total of 26 HIV-1-positive and 18 HIV-1-negative Dutch individuals were stimulated with CD3 monoclonal antibody (MAb) alone, a combination of CD3 and CD28 MAbs, or phytohemagglutinin. BrdU incorporation after 3 days of stimulation with a combination of CD3 and CD28 MAbs correlated excellently with the [3H]TdR incorporation in both study groups (HIV-1 positives, r = 0.96; HIV-1 negatives,r = 0.83). A significant correlation of absolute numbers of T cells expressing CD38 with [3H]TdR incorporation, both in HIV-1-positive (r = 0.96) and HIV-1-negative (r = 0.84) individuals, was also observed under these conditions. The results of this study indicate that determination of both the number of CD38-positive T cells and BrdU incorporation can be used as alternative techniques to measure the in vitro T-cell proliferative capacity. The measurement of CD38 expression on T cells provides the additional possibility to further characterize the proliferating T-cell subsets for expression of other surface markers.

scholarly journals Alprazolam Prompts HIV-1 Transcriptional Reactivation and Enhances CTL Response Through RUNX1 Inhibition and STAT5 Activation

2021 ◽  
Vol 12 ◽  
Author(s):  
Angel Lin ◽  
Weam Othman Elbezanti ◽  
Alexis Schirling ◽  
Adel Ahmed ◽  
Rachel Van Duyne ◽  
...  
Keyword(s):  
Cytotoxic T Cells ◽  
Viral Promoter ◽  
Immune Clearance ◽  
Significant Challenge ◽  
Ideal Candidate ◽  
Significant Barrier ◽  
Shock And Kill ◽  
Transcriptional Reactivation ◽  
Potential Use ◽  
Hiv 1

The HIV-1 pandemic is a significant challenge to the field of medicine. Despite advancements in antiretroviral (ART) development, 38 million people worldwide still live with this disease without a cure. A significant barrier to the eradication of HIV-1 lies in the persistently latent pool that establishes early in the infection. The “shock and kill” strategy relies on the discovery of a latency-reversing agent (LRA) that can robustly reactivate the latent pool and not limit immune clearance. We have found that a benzodiazepine (BDZ), that is commonly prescribed for panic and anxiety disorder, to be an ideal candidate for latency reversal. The BDZ Alprazolam functions as an inhibitor of the transcription factor RUNX1, which negatively regulates HIV-1 transcription. In addition to the displacement of RUNX1 from the HIV-1 5′LTR, Alprazolam potentiates the activation of STAT5 and its recruitment to the viral promoter. The activation of STAT5 in cytotoxic T cells may enable immune activation which is independent of the IL-2 receptor. These findings have significance for the potential use of Alprazolam in a curative strategy and to addressing the neuroinflammation associated with neuroHIV-1.

Sign in / Sign up

Export Citation Format

Share Document