scholarly journals Human Immunodeficiency Virus (HIV)-Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children

2018 ◽  
Vol 8 (5) ◽  
pp. 433-438 ◽  
Author(s):  
Salvatore Rocca ◽  
Paola Zangari ◽  
Nicola Cotugno ◽  
Anita De Rossi ◽  
Bridget Ferns ◽  
...  
Keyword(s):  
Viral Proteins ◽  
Antibody Responses ◽  
Hiv Dna ◽  
Art Initiation ◽  
Therapy Initiation ◽  
Immunodeficiency Virus ◽  
Dna Size ◽  
Hiv 1 ◽  
Plasma Assay

Different specific antibody responses against 10 HIV-1 viral proteins detected by Western blot, plasma assay on a very small amount of plasma (20 μL) can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children.

scholarly journals Persistent Antibody Responses but Declining Cytotoxic T-Lymphocyte Responses to Multiple Human Immunodeficiency Virus Type 1 Antigens in a Long-Term Nonprogressing Individual with a Defective p17 Proviral Sequence and No Detectable Viral RNA Expression

1998 ◽  
Vol 72 (4) ◽  
pp. 3472-3474 ◽  
Author(s):  
James M. Binley ◽  
Xia Jin ◽  
Yaoxing Huang ◽  
Linqi Zhang ◽  
Yunzhen Cao ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Antibody Responses ◽  
The Past ◽  
Immunodeficiency Virus ◽  
Lymphocyte Responses ◽  
Hiv 1

ABSTRACT Long-term nonprogressor AD-18 has been infected with human immunodeficiency virus type 1 (HIV-1) for at least 16 years. During the past 5 years, he has had undetectable levels of plasma viremia, and HIV-1 cannot be isolated from him. Sequencing of proviral DNA indicates that the only HIV-1 sequences that can be identified in AD-18 have gross defects in the p17-encoding regions of the gag gene (Y. Huang, L. Zhang, and D. D. Ho, Virology 240:36–49, 1998). However, AD-18 has strong, sustained antibody responses to several HIV-1 antigens, including p17. Cytotoxic T-lymphocyte responses to Env and Gag antigens have gradually diminished over the past 4 years, at a time when the titers of antibodies to the same proteins have remained stable. We discuss what these observations might mean for the generation and maintenance of immunological memory.

scholarly journals Immunogenicity of HIV-1-Based Virus-Like Particles with Increased Incorporation and Stability of Membrane-Bound Env

Vaccines ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 239
Author(s):  
Christopher A. Gonelli ◽  
Hannah A. D. King ◽  
Charlene Mackenzie ◽  
Secondo Sonza ◽  
Rob J. Center ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Neutralization Activity ◽  
Virus Like Particles ◽  
Antibody Isotypes ◽  
Immunodeficiency Virus ◽  
Proline Substitution ◽  
Membrane Bound ◽  
Antibody Epitopes ◽  
Hiv 1

An optimal prophylactic vaccine to prevent human immunodeficiency virus (HIV-1) transmission should elicit protective antibody responses against the HIV-1 envelope glycoprotein (Env). Replication-incompetent HIV-1 virus-like particles (VLPs) offer the opportunity to present virion-associated Env with a native-like structure during vaccination that closely resembles that encountered on infectious virus. Here, we optimized the incorporation of Env into previously designed mature-form VLPs (mVLPs) and assessed their immunogenicity in mice. The incorporation of Env into mVLPs was increased by replacing the Env transmembrane and cytoplasmic tail domains with those of influenza haemagglutinin (HA-TMCT). Furthermore, Env was stabilized on the VLP surface by introducing an interchain disulfide and proline substitution (SOSIP) mutations typically employed to stabilize soluble Env trimers. The resulting mVLPs efficiently presented neutralizing antibody epitopes while minimizing exposure of non-neutralizing antibody sites. Vaccination of mice with mVLPs elicited a broader range of Env-specific antibody isotypes than Env presented on immature VLPs or extracellular vesicles. The mVLPs bearing HA-TMCT-modified Env consistently induced anti-Env antibody responses that mediated modest neutralization activity. These mVLPs are potentially useful immunogens for eliciting neutralizing antibody responses that target native Env epitopes on infectious HIV-1 virions.

Combined Genotypes of CCR5, CCR2, SDF1, and HLA Genes Can Predict the Long-Term Nonprogressor Status in Human Immunodeficiency Virus-1–Infected Individuals

Blood ◽  
1999 ◽  
Vol 93 (3) ◽  
pp. 936-941 ◽  
Author(s):  
Magdalena Magierowska ◽  
Ioannis Theodorou ◽  
Patrice Debré ◽  
Françoise Sanson ◽  
Brigitte Autran ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Chemokine Receptor ◽  
Multivariate Logistic Regression Model ◽  
Hla B27 ◽  
Hla Alleles ◽  
Immunodeficiency Virus ◽  
Combined Genotypes ◽  
Hiv 1

Abstract Human immunodeficiency virus (HIV)-1–infected long-term nonprogressors (LT-NP) represent less than 5% of HIV-1–infected patients. In this work, we tried to understand whether combined genotypes of CCR5-▵32, CCR2-64I, SDF1-3′A and HLA alleles can predict the LT-NP status. Among the chemokine receptor genotypes, only the frequency of the CCR5-▵32 allele was significantly higher in LT-NP compared with the group of standard progressors. The predominant HLA alleles in LT-NP were HLA-A3, HLA-B14, HLA-B17, HLA-B27, HLA-DR6, and HLA-DR7. A combination of both HLA and chemokine receptor genotypes integrated in a multivariate logistic regression model showed that if a subject is heterozygous for CCR5-▵32 and homozygous for SDF1 wild type, his odds of being LT-NP are increased by 16-fold, by 47-fold when a HLA-B27 allele is present with HLA-DR6 absent, and by 47-fold also if at least three of the following alleles are present: HLA-A3, HLA-B14, HLA-B17, HLA-DR7. This model allowed a correct classification of 70% of LT-NPs and 81% of progressors, suggesting that the host’s genetic background plays an important role in the evolution of HIV-1. The chemokine receptor and chemokine genes along with the HLA genotype can serve as predictors of HIV-1 outcome for classification of HIV-1–infected subjects as LT-NPs or progressors.

scholarly journals Grossly Defective nef Gene Sequences in a Human Immunodeficiency Virus Type 1-Seropositive Long-Term Nonprogressor

1998 ◽  
Vol 72 (5) ◽  
pp. 3646-3657 ◽  
Author(s):  
Roberto Salvi ◽  
Anna Rosa Garbuglia ◽  
Antonino Di Caro ◽  
Simonetta Pulciani ◽  
Francesco Montella ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Length Polymorphism ◽  
Mononuclear Cells ◽  
Polymorphism Analysis ◽  
Immunodeficiency Virus ◽  
Peripheral Mononuclear Cells ◽  
Hiv 1

ABSTRACT We have been investigating a long-term nonprogressor who was found to be human immunodeficiency virus type 1 (HIV-1) seropositive in 1985 and has survived with stable CD4+ T-cell counts (>1,000 CD4 cells/μl) without any AIDS-related illness. We have previously reported that repeated attempts to measure HIV-1 RNA in the peripheral mononuclear cells obtained from this subject have invariably failed. In the present study, we have analyzed the molecular nature of the HIV-1 quasispecies infecting this patient by PCR amplification of two proviral regions, the 5′ long terminal repeat (5′LTR)/gagleader and the nef gene, directly from fresh uncultured peripheral mononuclear cells, followed by length polymorphism analysis (with 1994, 1995, and 1996 samples) and sequencing (with a 1996 sample). Only proviral forms with nef deletions were revealed by length polymorphism analysis in samples from all three time points. Sequence analysis of the nef gene from the 1996 sample confirmed the presence of similar proviral quasispecies characterized by the presence of several deletions located in thenef-alone and the nef/U3 overlapping regions. Length polymorphism analysis of the 5′LTR/gag leader region suggested the existence of two major quasispecies populations, one characterized by the presence of forms carrying deletions in the U3 region and the other showing a completely intact, full-length 5′LTR. Evidence of the role of nef gene defects in long-term survival of HIV-1-infected patients has been provided so far in two independent investigations involving patients infected with HIV through blood transfusion. Here we show the existence of a similar condition in a subject who acquired HIV-1 seropositivity through the sexual route.

scholarly journals Neutralizing Antibody Responses in Acute Human Immunodeficiency Virus Type 1 Subtype C Infection

2007 ◽  
Vol 81 (12) ◽  
pp. 6187-6196 ◽  
Author(s):  
E. S. Gray ◽  
P. L. Moore ◽  
I. A. Choge ◽  
J. M. Decker ◽  
F. Bibollet-Ruche ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Subtype C ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT The study of the evolution and specificities of neutralizing antibodies during the course of human immunodeficiency virus type 1 (HIV-1) infection may be important in the discovery of possible targets for vaccine design. In this study, we assessed the autologous and heterologous neutralization responses of 14 HIV-1 subtype C-infected individuals, using envelope clones obtained within the first 2 months postinfection. Our data show that potent but relatively strain-specific neutralizing antibodies develop within 3 to 12 months of HIV-1 infection. The magnitude of this response was associated with shorter V1-to-V5 envelope lengths and fewer glycosylation sites, particularly in the V1-V2 region. Anti-MPER antibodies were detected in 4 of 14 individuals within a year of infection, while antibodies to CD4-induced (CD4i) epitopes developed to high titers in 12 participants, in most cases before the development of autologous neutralizing antibodies. However, neither anti-MPER nor anti-CD4i antibody specificity conferred neutralization breadth. These data provide insights into the kinetics, potency, breadth, and epitope specificity of neutralizing antibody responses in acute HIV-1 subtype C infection.

scholarly journals Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies

Vaccines ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 76 ◽  
Author(s):  
Mitch Brinkkemper ◽  
Kwinten Sliepen
Keyword(s):  
Envelope Glycoprotein ◽  
Neutralizing Antibodies ◽  
Critical Role ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Broadly Neutralizing Antibodies ◽  
Viral Membrane ◽  
Immunodeficiency Virus ◽  
Hiv 1

The enormous sequence diversity between human immunodeficiency virus type 1 (HIV-1) strains poses a major roadblock for generating a broadly protective vaccine. Many experimental HIV-1 vaccine efforts are therefore aimed at eliciting broadly neutralizing antibodies (bNAbs) that are capable of neutralizing the majority of circulating HIV-1 strains. The envelope glycoprotein (Env) trimer on the viral membrane is the sole target of bNAbs and the key component of vaccination approaches aimed at eliciting bNAbs. Multimeric presentation of Env on nanoparticles often plays a critical role in these strategies. Here, we will discuss the different aspects of nanoparticles in Env vaccination, including recent insights in immunological processes underlying their perceived advantages, the different nanoparticle platforms and the various immunogenicity studies that employed nanoparticles to improve (neutralizing) antibody responses against Env.

scholarly journals HIV-1 Transcription but Not Intact Provirus Levels are Associated With Systemic Inflammation

2020 ◽  
Author(s):  
Alex Olson ◽  
Carolyn Coote ◽  
Jennifer E Snyder-Cappione ◽  
Nina Lin ◽  
Manish Sagar
Keyword(s):  
Infected Cell ◽  
Cell Lines ◽  
Mononuclear Cells ◽  
Rna Expression ◽  
Peripheral Blood Mononuclear ◽  
Hiv Dna ◽  
Immunodeficiency Virus ◽  
Latently Infected ◽  
Hiv 1 ◽  
D Dimer

Abstract Individuals infected with human immunodeficiency virus (HIV) 1 have increased inflammation, which has been associated with age-associated diseases. Plasma markers, cell-associated virus levels, and ability to stimulate RNA transcription in latently infected cell lines was examined in younger and older HIV-1–infected individuals with suppressed virus. Cell-associated RNA, but not intact provirus level, had positive correlation with plasma D-dimer levels. Compared with the younger group, the older group had higher D-dimer levels and a trend toward more cell-associated RNA but similar levels of intact proviruses. Even though all measured inflammatory markers were relatively higher in the older group, this greater inflammation did not induce more HIV-1 transcription in latently infected cell lines. Inflammation and HIV-1 RNA expression increase with age despite similar levels of intact infectious HIV DNA. While plasma inflammation is correlated with HIV-1 RNA expression in peripheral blood mononuclear cells, it does not induce HIV-1 transcription in latently infected cell lines.

Characterization of drug resistance and the defective HIV reservoir in virally suppressed vertically infected children in Mali

2020 ◽  
Vol 75 (5) ◽  
pp. 1272-1279
Author(s):  
Josephine Brice ◽  
Mariam Sylla ◽  
Nathalie Desire ◽  
Sophie Sayon ◽  
Fatoumata Telly ◽  
...  
Keyword(s):  
Stop Codon ◽  
Dried Blood Spots ◽  
Viral Population ◽  
Genotypic Resistance ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
Art Initiation ◽  
High Prevalence ◽  
Resistance Patterns ◽  
Hiv 1

Abstract Background In the perspective of ART-free HIV remission, vertically infected children treated with suppressive ART from early infancy represent an optimal population model to better understand the genetic complexity of the reservoir. Objectives To evaluate the proportion of defective viral population and the genotypic resistance patterns in cell-associated HIV DNA. Methods In a cohort including 93 ART-treated vertically HIV-infected (VHIV) children in Mali with plasma HIV-1 RNA ≤50 copies/mL for at least 6 months, we studied total HIV DNA, percentage of defective genomes and resistance by reverse transcriptase and protease bulk sequencing from whole blood in dried blood spots. Results Children had a median age of 9.9 years at the time of inclusion (IQR = 7.6–13.4) and 3.3 years (IQR = 2–7) at ART initiation; median ART duration was 5.5 years (IQR = 3.7–7.3). The median level of total HIV DNA was 470 copies/106 cells with one patient presenting undetectable HIV DNA (<66 copies/106 cells). We observed the presence of at least one stop codon in viruses from 34 patients (37%). The presence of stop codons was not correlated with the level of HIV DNA or duration of ART. We showed a high prevalence of HIV-1 resistance in DNA with 26% of children harbouring virus resistant to at least one NRTI and 40% to at least one NNRTI. Conclusions While these VHIV children were successfully treated for a long time, they showed high prevalence of resistance in HIV DNA and a moderate defective HIV reservoir.

scholarly journals Loss of primitive hematopoietic progenitors in patients with human immunodeficiency virus infection

Blood ◽  
1996 ◽  
Vol 88 (12) ◽  
pp. 4568-4578 ◽  
Author(s):  
A Marandin ◽  
A Katz ◽  
E Oksenhendler ◽  
M Tulliez ◽  
F Picard ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Human Immunodeficiency Virus ◽  
Long Term Culture ◽  
Cd34 Cells ◽  
Immunodeficiency Virus ◽  
Cell Fractions ◽  
Cd38 Antigen ◽  
Hiv 1

A number of hematologic abnormalities, including cytopenias, have been observed in patients with human immunodeficiency virus (HIV) infection. To elucidate their mechanisms, primitive cells from bone marrow aspirates of 21 patients with HIV-1 infection were quantitated by flow cytometry. The mean percentage of CD34+ cells is not significantly altered in HIV-1-infected patients in comparison with HIV-1- seronegative controls. In contrast, two- and three-color immunofluorescence analysis showed that in all HIV-1 samples, most CD34+ cells coexpressed the CD38 antigen. The proportion of HIV-1- derived CD34+ cells that did not express the CD38 antigen was significantly lower (HIV-1+: mean, 1.73%; controls: mean, 14%; P < .0005) than in controls. Moreover, of Thy-1+ cells, the proportion of CD34+ cells was twofold lower in HIV-1-infected patients (HIV-1+: mean, 12%; controls, 25%, P < .0005), which suggests that phenotypically primitive cells are depleted in HIV-1 infection. In vitro functional analysis in long-term cultures of sorted CD34+ cells from seven HIV-1 patients showed that CD34+ cells from HIV-1 patients generated much fewer colonies both in the nonadherent and adherent layers than CD34+ cells from controls after 5 weeks of culture (10-fold and four-fold less, respectively). Precise long-term culture initiating cell (LTC-IC) frequency in the CD34+ cell population was determined in three patients by limiting dilution and was markedly decreased in comparison to that of normal controls (from twofold to > sevenfold decreased). To determine if primitive cells were infected by HIV-1, both methylcellulose colonies generated from long-term culture of CD34+ cells and various CD34+ cell fractions purified by flow cytometry were evaluated for the presence of HIV-1 by polymerase chain reaction (PCR). Progeny from long-term culture was HIV-1-negative in three samples. In addition, using a sensitive PCR technique, the HIV-1 genome could not be detected in CD34+, CD34+/CD38-, and CD34+/CD4+ cells. These data show that hematologic disorders in HIV disease may be the consequence of a deficit of primitive cells. However, direct infection of these cells by HIV-1 does not seem to be responsible for this defect.

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