scholarly journals HIV-1C env and gag Variation in the Cerebrospinal Fluid and Plasma of Patients with HIV-Associated Cryptococcal Meningitis in Botswana

Viruses ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 1404
Author(s):  
Nametso Kelentse ◽  
Sikhulile Moyo ◽  
Mompati L. Mogwele ◽  
Doreen Ditshwanelo ◽  
Baitshepi Mokaleng ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cryptococcal Meningitis ◽  
Cytotoxic T Lymphocyte ◽  
Population Based ◽  
Plasma Samples ◽  
Plasma Virus ◽  
Significant Difference ◽  
Hiv Eradication ◽  
Ctl Escape ◽  
Hiv 1

HIV-1 compartmentalization in reservoir sites remains a barrier to complete HIV eradication. It is unclear whether there is variation in HIV-1 env and gag between cerebrospinal fluid (CSF) and plasma of individuals with HIV-associated cryptococcal meningitis (CM). We compared HIV-1 env characteristics and the gag cytotoxic T-lymphocyte (CTL) escape mutations from CSF and plasma samples. Employing population-based Sanger sequencing, we sequenced HIV-1 env from CSF of 25 patients and plasma of 26 patients. For gag, 15 CSF and 21 plasma samples were successfully sequenced. Of these, 18 and 9 were paired env and gag CSF/plasma samples, respectively. There was no statistically significant difference in the proportion of CCR5-using strains in the CSF and plasma, (p = 0.50). Discordant CSF/plasma virus co-receptor use was found in 2/18 pairs (11.1%). The polymorphisms in the HIV-1 V3 loop were concordant between the two compartments. From the HIV-1 gag sequences, three pairs had discordant CTL escape mutations in three different epitopes of the nine analyzed. These findings suggest little variation in the HIV-1 env between plasma and CSF and that the CCR5-using strains predominate in both compartments. HIV-1 gag CTL escape mutations also displayed little variation in CSF and plasma suggesting similar CTL selective pressure.

scholarly journals Kinetics of HIV-1 in cerebrospinal fluid and plasma in cryptococcal meningitis

2012 ◽  
Vol 4 (1) ◽  
pp. 30 ◽  
Author(s):  
Diego M. Cecchini ◽  
Ana M. Cañizal ◽  
Haroldo Rojas ◽  
Alicia Arechavala ◽  
Ricardo Negroni ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Viral Load ◽  
Cryptococcal Meningitis ◽  
Clinical Course ◽  
Plasma Concentrations ◽  
Plasma Samples ◽  
Viral Kinetics ◽  
Opportunistic Disease ◽  
Kinetics Of ◽  
Hiv 1

In order to determine HIV-1 kinetics in cerebrospinal fluid (CSF) and plasma in patients with cryptococcal meningitis (CM), we undertook a prospective collection of paired CSF/plasma samples from antiretroviral therapy- free HIV-infected patients with CM. Samples were obtained at baseline (S1) and at the second (S2) and third (S3) weeks of antifungal therapy. HIV-1 CSF concentrations were significantly lower in both S2 and S3 with respect to S1. Plasma concentrations remained stable. HIV-1 concentrations were higher in plasma than CSF in all cases. Patients who survived the episode of CM (but not those who died) showed a decrease in CSF viral load, what suggests different viral kinetics of HIV-1 in the CSF according to the clinical course of this opportunistic disease.

scholarly journals Cerebrospinal Fluid HIV-1 Viral Load During Treatment of Cryptococcal Meningitis

2010 ◽  
Vol 53 (5) ◽  
pp. 668-669 ◽  
Author(s):  
Annemarie E Brouwer ◽  
Praprit Teparrukkul ◽  
Adul Rajanuwong ◽  
Wirongrong Chierakul ◽  
Weera Mahavanakul ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Viral Load ◽  
Cryptococcal Meningitis ◽  
Hiv 1

scholarly journals Unique Acquisition of Cytotoxic T-Lymphocyte Escape Mutants in Infant Human Immunodeficiency Virus Type 1 Infection

2005 ◽  
Vol 79 (18) ◽  
pp. 12100-12105 ◽  
Author(s):  
Thillagavathie Pillay ◽  
Hua-Tang Zhang ◽  
Jan W. Drijfhout ◽  
Nicola Robinson ◽  
Helen Brown ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Viral Escape ◽  
Immunodeficiency Virus ◽  
Ctl Escape ◽  
Hiv 1

ABSTRACT The role of cytotoxic T-lymphocyte (CTL) escape in rapidly progressive infant human immunodeficiency virus type 1 (HIV-1) infection is undefined. The data presented here demonstrate that infant HIV-1-specific CTL can select for viral escape variants very early in life. These variants, furthermore, may be selected specifically in the infant, despite the same CTL specificity being present in the mother. Additionally, pediatric CTL activity may be compromised both by the transmission of maternal escape variants and by mother-to-child transmission of escape variants that originally arose in the father. The unique acquisition of these CTL escape forms may help to explain the severe nature of some pediatric HIV infections.

scholarly journals Comparison of Human Immunodeficiency Virus Type 1 RNA Sequence Heterogeneity in Cerebrospinal Fluid and Plasma

2000 ◽  
Vol 38 (12) ◽  
pp. 4637-4639 ◽  
Author(s):  
Yi-Wei Tang ◽  
Joe T.-J. Huong ◽  
Robert M. Lloyd ◽  
Paul Spearman ◽  
David W. Haas
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cerebrospinal Fluid ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Plasma Samples ◽  
Sequence Heterogeneity ◽  
Immunodeficiency Virus ◽  
Viral Sequences ◽  
Hiv 1

The source of human immunodeficiency virus type 1 (HIV-1) RNA in cerebrospinal fluid (CSF) during HIV-1 infection is uncertain. The sequence heterogeneity of HIV-1 RNA in simultaneous CSF and plasma samples was characterized for five patients at the baseline and during the first week of antiretroviral therapy by two commercial genotyping methodologies. In individual subjects, the sequences in CSF samples differed significantly from those in plasma. In contrast, the viral sequences in CSF at the baseline did not differ from the sequences in CSF during treatment. Similarly, viral sequences in plasma did not vary over this interval. This study provides evidence that HIV-1 RNA in CSF and plasma arise from distinct compartments.

scholarly journals Deep sequencing of the HIV-1 polymerase gene for characterisation of cytotoxic T-lymphocyte epitopes during early and chronic disease stages

2021 ◽  
Author(s):  
Paballo Nkone ◽  
Shayne Loubser ◽  
Thomas C. Quinn ◽  
Andrew D. Redd ◽  
Arshad Ismail ◽  
...  
Keyword(s):  
T Lymphocyte ◽  
Deep Sequencing ◽  
Sanger Sequencing ◽  
Cytotoxic T Lymphocyte ◽  
Sequencing Data ◽  
Subtype C ◽  
Ctl Epitopes ◽  
Significant Difference ◽  
Minority Variant ◽  
Hiv 1

Abstract Background Despite multiple attempts, there is still no effective HIV-1 vaccine available. The HIV-1 polymerase (pol) gene is highly conserved and encodes cytotoxic T-lymphocyte (CTL) epitopes. In this study, deep sequencing was employed for characterisation of HIV-1 Pol CTL epitopes in mostly paired samples obtained during early and chronic stages of infection. Deep sequencing data was then compared to Sanger sequencing data only in samples obtained at baseline. Results Fifty-two participants were enrolled in the study. Their median age was 28 years (interquartile range: 24–32 years) and the majority of participants (92.3%) were female. Illumina minority variant analysis identified a significantly higher number of CTL epitopes (n = 65) compared to epitopes (n = 8) identified through Sanger sequencing. Most of the identified epitopes mapped to reverse transcriptase (RT) and integrase (IN) regardless of the method of sequencing. There was a significantly higher proportion of minority variant epitopes in RT (n = 39, 60.0%) compared to IN (n = 17, 26.2%) and PR (n = 9, 13.8%), p = 0.002 and < 0.0001, respectively. However, no significant difference was observed between the proportion of minority variant epitopes in IN versus PR, p = 0.06. Some epitopes were detected in either early or chronic HIV-1 infection whereas others were detected in both stages. Different distribution patterns of minority variant epitopes were observed in sample pairs; with some increasing or decreasing over time, while others remained constant. Some of the identified epitopes have not been previously reported for HIV-1 subtype C. There were also variants that could not be mapped to reported CTL epitopes in the Los Alamos HIV database. Conclusion Deep sequencing revealed many Pol CTL epitopes, including some not previously reported for HIV-1 subtype C. The findings of this study support the inclusion of RT and IN epitopes in HIV-1 vaccine candidates as these proteins harbour many CTL epitopes. Variants that were not mapped within CTL epitopes could represent new epitopes.

scholarly journals Anti-V2 Antibody Deficiency in Individuals Infected With HIV-1

2018 ◽  
Author(s):  
Lily Liu ◽  
Liuzhe Li ◽  
Aubin Nanfack ◽  
Luzia M. Mayr ◽  
Sonal Soni ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Hiv Vaccine ◽  
Phase Iii ◽  
Dominant Factor ◽  
Plasma Samples ◽  
Electrostatic Charges ◽  
Glycosylation Sites ◽  
Significant Difference ◽  
Hiv 1 ◽  
Rv144 Vaccine

ABSTRACTThe positive correlation of high levels of plasma anti-V2 antibodies (Abs) with protective immunity in the Phase III anti-HIV RV144 vaccine trial generated interest in the induction of these Abs for HIV vaccine development. We analyzed plasma samples from 79 chronically infected Cameroonian individuals for Ab reactivity against three V1V2 fusion proteins and five cyclic V2 peptides and found that HIV-1 infection induces different levels of anti-V2 Abs. While the majority of plasma samples reacted strongly with one or more V2 antigens, 10% (8) of the samples were nonreactive. Deficiency of anti-V2 Abs was consistently found in longitudinal plasma samples tested over 8 to 54 months of HIV infection. There was a strong correlation between binding activities of plasma anti-V2 Abs and anti-gp120 and anti-gp41 Abs, suggesting that deficiency of V2 Abs could be related, in part, to a limited ability to elicit strong Ab responses. Analysis of gp120 sequences revealed that the V2 region of viruses from donors with V2-deficient versus V2-reactive Abs displayed a tendency toward longer length, more glycans, and lower isoelectric point and charge. No differences between these two patient groups were noted in the same parameters measured in the V1 region. These data suggest that immunogens containing a shorter V2 region with fewer glycosylation sites and higher electrostatic charges would be beneficial for induction of anti-V2 Abs, but the ability to mount a strong general Ab response to HIV-1 appears to be a dominant factor.IMPORTANCEThe results of the RV144 vaccine clinical trial showed a correlation between plasma Abs against a V1V2 fusion protein and a decreased risk of acquiring HIV-1 infection. This turned the focus of some HIV vaccine design to the induction of elevated levels of anti-V2 Abs to increase vaccine efficacy. In plasma samples from Cameroonian individuals infected with HIV-1, we observed broad variations in levels of anti-V2 Abs, and 8 of the 79 plasma samples tested displayed substantial deficiency of V2 Abs. Sequence analysis of the V2 region from plasma viruses and multivariate analyses of V2 characteristics showed a significant difference in several features between V2-deficient and V2-reactive plasma Abs. These results suggest that HIV vaccine immunogens containing a V2 region with shorter length, fewer glycosylation sites, and higher electrostatic charges may be beneficial for induction of a higher level of anti-V2 Abs and thus contribute to HIV vaccine efficacy.

scholarly journals Individuals with HIV-1 Subtype C Infection and Cryptococcal Meningitis Exhibit Viral Genetic Intermixing of HIV-1 Between Plasma and Cerebrospinal Fluid and a High Prevalence of CXCR4-Using Variants

2018 ◽  
Vol 34 (7) ◽  
pp. 607-620 ◽  
Author(s):  
Katlego Sojane ◽  
Richard T. Kangethe ◽  
Christina C. Chang ◽  
Mahomed-Yunus S. Moosa ◽  
Sharon R. Lewin ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Cryptococcal Meningitis ◽  
Subtype C ◽  
High Prevalence ◽  
Hiv 1

scholarly journals Global Database-Driven Assessment of HIV-1 Adaptation to the Immune Repertoires of Human Populations

2015 ◽  
Vol 89 (20) ◽  
pp. 10693-10695 ◽  
Author(s):  
Aram Karakas ◽  
Zabrina L. Brumme ◽  
Art F. Y. Poon
Keyword(s):  
T Lymphocyte ◽  
Cytotoxic T Lymphocyte ◽  
Human Leukocyte ◽  
Human Populations ◽  
Hla Alleles ◽  
Global Database ◽  
Leukocyte Antigen ◽  
Ctl Escape ◽  
The Relationship ◽  
Hiv 1

Associations between HIV-1 cytotoxic T lymphocyte (CTL) escape mutations and their restricting human leukocyte antigen (HLA) alleles imply that HIV could adapt to divergent HLA repertoires of human populations globally. Using publicly available databases, we examine the relationship between the frequencies of 19 experimentally validated CTL escape mutations in HIV-1 reverse transcriptase and their restricting HLA alleles in 59 countries. From these extensive data, we find evidence of differential HIV adaptations to human populations at only a limited number of the studied epitope sites.

scholarly journals HIV‐1 Chemokine Coreceptor Utilization in Paired Cerebrospinal Fluid and Plasma Samples: A Survey of Subjects with Viremia

2005 ◽  
Vol 191 (6) ◽  
pp. 890-898 ◽  
Author(s):  
Serena S. Spudich ◽  
Wei Huang ◽  
Annelie C. Nilsson ◽  
Christos J. Petropoulos ◽  
Teri J. Liegler ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Plasma Samples ◽  
Hiv 1

scholarly journals Control of HIV-1 in Elite Suppressors despite Ongoing Replication and Evolution in Plasma Virus

2010 ◽  
Vol 84 (14) ◽  
pp. 7018-7028 ◽  
Author(s):  
Karen A. O'Connell ◽  
Timothy P. Brennan ◽  
Justin R. Bailey ◽  
Stuart C. Ray ◽  
Robert F. Siliciano ◽  
...  
Keyword(s):  
Selective Pressure ◽  
De Novo ◽  
Cytotoxic T Lymphocyte ◽  
Hla Class I ◽  
Latent Reservoir ◽  
Elite Controllers ◽  
Plasma Virus ◽  
Longitudinal Plasma ◽  
Elite Suppressors ◽  
Hiv 1

ABSTRACT A subset of HIV-1-infected patients known as elite controllers or suppressors (ES) control the virus naturally. We have previously demonstrated sequence discordance between proviral and plasma gag clones in ES, much of which can be attributed to selective pressure from the host (J. R. Bailey, T. M. Williams, R. F. Siliciano, and J. N. Blankson, J. Exp. Med. 203:1357-1369, 2006). However, it is not clear whether ongoing viral replication continues in ES once the control of viremia has been established or whether selective pressure impacts this evolution. The cytotoxic T-lymphocyte (CTL) response in ES often targets Gag and frequently is superior to that of HIV-1 progressors, partially due to the HLA class I alleles B*57/5801 and B*27, which are overrepresented in ES. We therefore examined longitudinal plasma and proviral gag sequences from HLA-B*57/5801 and -B*27 ES. Despite the highly conserved nature of gag, we observed clear evidence of evolution in the plasma virus, largely due to synonymous substitutions. In contrast, evolution was rare in proviral clones, suggesting that ongoing replication in ES does not permit the significant reseeding of the latent reservoir. Interestingly, there was little continual evolution in CTL epitopes, and we detected de novo CTL responses to autologous viral mutants. Thus, some ES control viremia despite ongoing replication and evolution.

Sign in / Sign up

Export Citation Format

Share Document