Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia

Arcia, David; Ochoa, Rodrigo; Hernández, Juan Carlos; Álvarez, Cristiam M.; Díaz, Francisco J.; Velilla, Paula A.; Acevedo-Sáenz, Liliana

doi:10.1016/j.meegid.2018.07.001

Cited by 7 publications

(8 citation statements)

References 60 publications

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“…While some non-synonymous substitutions were observed before and after antibodies detection (H28K, M30R, A224P and A248G), some, such as V82I and Y86W were consistently identified after antibodies detection. V82I has been previously identified in studies among infected individuals[68,69]. This substitution among other things were associated with emergence of higher viral loads while Y86W was previously associated with HIV-1 clade B and E[70].…”

Section: Discussionmentioning

confidence: 91%

Non synonymous substitutions in HIV-1 GAG are frequent in epitopes outside the major hydrophobic region and associated with subtype differences

Olusola

Olaleye

Odaibo

2020

Preprint

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In 2018, an estimated 38 million people lived with HIV-1 infection resulting in 770,000 deaths. More than 50% of this infection and its associated deaths occurred in Sub-Saharan Africa. There is a need to develop an HIV-1 vaccine if the epidemic would be effectively controlled. Cytotoxic T Lymphocytes (CTL) epitopes within the Major Hydrophobic Region (MHR) have been shown to be highly immunogenic and immuno-dominant. These conserved epitopes have recently been the focus of vaccine studies. Despite the West African epicenter having one of the highest numbers of diverse circulating HIV-1 strains, very few longitudinal studies have checked the frequencies of CTL immune escape variants on epitopes within and without the MHR for HIV-1 strains circulating in the region. In this study, we describe non-synonymous substitutions within and without the MHR of HIV-1 GAG genes isolated from 10 infected Nigerians at the early stages of HIV-1 infection. Furthermore, we analyzed these substitutions longitudinally in five infected individuals from the early stages of infection up until when antibodies become detectable. We identified 3 non-synonymous substitutions within the MHR of HIV-1 GAG genes isolated from the early HIV infected individuals. Fourteen and nineteen mutations outside the MHR were observed before and after the detection of antibodies respectively while 4 mutations were found within the MHR. These substitutions include previously mapped CTL epitope immune escape mutants. CTL immune pressure likely leaves different footprints on HIV-1 GAG epitopes within and outside the MHR. This information is crucial for future vaccine designs for use in the West African region.

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Section: Discussionmentioning

confidence: 91%

Non synonymous substitutions in HIV-1 GAG are frequent in epitopes outside the major hydrophobic region and associated with subtype differences

Olusola

Olaleye

Odaibo

2020

Preprint

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“…In genome alignments of strains belonging to epitopes of HIV-1 subtype B, a high frequency of S53T substitution is observed ( 43 ). Since this variant circulates in a high proportion of the studied population, it was considered the wild type variant of the GC9 epitope (GC9 WT) ( 15 ). Furthermore, Gesprasert et al.…”

Section: Discussionmentioning

confidence: 99%

“…HLA-I typing was performed with genomic DNA extracted from PB through a phenol/chloroform DNA extraction protocol. In addition, HLA-A typing was performed by the sequence-specific oligonucleotide (SSO) technology, using the Lifecodes ® HLA-SSO Typing Kit (Immucor Transplant Diagnostics, Inc., Stanford, CT) and measured using the Luminex ® 100/200TMinstrument (Luminex, Austin, TX, USA), as was previously reported ( 15 ).…”

Section: Methodsmentioning

confidence: 99%

“…A previous study from our group demonstrated the adaptation of circulating HIV-1 strains from Medellín, Colombia, to the most prevalent HLA-I alleles in the population, HLA-A*02:01. Different mutations mapped into HLA-I-specific GC9 and SL9 epitopes associated with decreased or increased binding affinity towards HLA-A*02:01 were identified ( 15 ). Interestingly, our analyses showed that two different mutations in the HLA-A*02-restricted GC9 epitope, S54A, and S54T, significantly increased the epitope binding affinity towards HLA-A*02; also showed a mutation, Y79F/T84V/L85F, associated with low HLA-binding affinity in HLA-A*02-restricted SL9, which has been considered immunodominant epitope ( 16 ).…”

Section: Introductionmentioning

confidence: 99%

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Functional Profile of CD8+ T-Cells in Response to HLA-A*02:01-Restricted Mutated Epitopes Derived from the Gag Protein of Circulating HIV-1 Strains from Medellín, Colombia

et al. 2022

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CD8+ T-cells play a crucial role in the control of HIV replication. HIV-specific CD8+ T-cell responses rapidly expand since the acute phase of the infection, and it has been observed that HIV controllers harbor CD8+ T-cells with potent anti-HIV capacity. The development of CD8+ T-cell-based vaccine against HIV-1 has focused on searching for immunodominant epitopes. However, the strong immune pressure of CD8+ T-cells causes the selection of viral variants with mutations in immunodominant epitopes. Since HIV-1 mutations are selected under the context of a specific HLA-I, the circulation of viral variants with these mutations is highly predictable based on the most prevalent HLA-I within a population. We previously demonstrated the adaptation of circulating strains of HIV-1 to the HLA-A*02 molecule by identifying mutations under positive selection located in GC9 and SL9 epitopes derived from the Gag protein. Also, we used an in silico prediction approach and evaluated whether the mutations found had a higher or lower affinity to the HLA-A*02. Although this strategy allowed predicting the interaction between mutated peptides and HLA-I, the functional response of CD8+ T-cells that these peptides induce is unknown. In the present work, peripheral blood mononuclear cells from 12 HIV-1+ HLA-A*02:01+ individuals were stimulated with the mutated and wild-type peptides derived from the GC9 and SL9 epitopes. The functional profile of CD8+ T-cells was evaluated using flow cytometry, and the frequency of subpopulations was determined according to their number of functions and the polyfunctionality index. The results suggest that the quality of the response (polyfunctionality) could be associated with the binding affinity of the peptide to the HLA molecule, and the functional profile of specific CD8+ T-cells to mutated epitopes in individuals under cART is maintained.

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“…The plasma viral load was determined using the commercial assay RT-PCR Ampliprep Cobas Amplicor (Roche, Indianapolis, IN, USA; detection limit of 20 copies/mL), according to the manufacturer’s instructions. The frequency of peripheral blood CD4+ T cells was determined by flow cytometry, as previously reported [41]. Briefly, the peripheral blood was incubated with specific monoclonal antibodies at room temperature in the dark.…”

Section: Methodsmentioning

confidence: 99%

Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection

Feria-Garzón

Rugeles

Hernández

et al. 2019

IJMS

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Background: HIV-1 induces an uncontrolled inflammatory response of several immune components, such as inflammasomes. These molecular complexes, associated with Toll-like receptor (TLR) activity, induce the maturation and release of IL-1β and IL-18 and eventually induce pyroptosis. It has been previously demonstrated that HIV induces inflammasome activation, which is significantly lower in the gastrointestinal tissue and blood from people living with HIV-1 with spontaneous control of viral replication. Therefore, immunomodulatory agents could be useful in improving HIV prognosis. Objective: To evaluate the potential inhibitory effect of sulfasalazine (SSZ) on inflammasomes and TLRs in peripheral blood mononuclear cells (PBMCs) from people living with HIV and healthy donors. Methods: PBMCs were obtained from 15 people living with HIV and 15 healthy donors. Cells were stimulated with agonists of TLRs and inflammasomes and subsequently treated with SSZ. The concentration of IL-1β and the relative expression of NLRP3, NLRC4, NLRP1, AIM2, ASC, Caspase-1, IL-1β, and IL-18 were quantified. Results: Cells treated with SSZ exhibited a decreased IL-1β production after inflammasome and TLR stimulation, as well as regulation of inflammasome-related genes, in both people with HIV and healthy individuals. The concentration of IL-1β was positively correlated with the CD4+ T-cell count and negatively with the viral load. Conclusion: Our results suggest that SSZ has an immunomodulatory effect on inflammasome and TLR activation that depends on the clinical HIV status.

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Potential immune escape mutations under inferred selection pressure in HIV-1 strains circulating in Medellín, Colombia

Cited by 7 publications

References 60 publications

Non synonymous substitutions in HIV-1 GAG are frequent in epitopes outside the major hydrophobic region and associated with subtype differences

Non synonymous substitutions in HIV-1 GAG are frequent in epitopes outside the major hydrophobic region and associated with subtype differences

Functional Profile of CD8+ T-Cells in Response to HLA-A*02:01-Restricted Mutated Epitopes Derived from the Gag Protein of Circulating HIV-1 Strains from Medellín, Colombia

Sulfasalazine as an Immunomodulator of the Inflammatory Process during HIV-1 Infection

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