HIV exposed seronegative (HESN) compared to HIV infected individuals have higher frequencies of telomeric Killer Immunoglobulin-like Receptor (KIR) B motifs; Contribution of KIR B motif encoded genes to NK cell responsiveness

Jackson, Elise; Zhang, Cindy Xinyu; Kiani, Zahra; Lisovsky, Irene; Tallon, B; Corpo, Alexa Del; Gilbert, Louise; Bruneau, Julie; Thomas, Réjean; Côté, Pierre; Trottier, Benôit; LeBlanc, Roger; Rouleau, Danielle; Tremblay, Cécile; Tsoukas, Christos; Routy, Jean‐Pierre; Ni, Xiaoling; Mabanga, Tsoarello; Bernard, Nicole F.

doi:10.1371/journal.pone.0185160

Cited by 15 publications

(16 citation statements)

References 64 publications

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“…The presence of the activator receptor KIR3DS1 on NK cells in combination with HLA-Bw4-I80, is one of the most reported phenotype associated with delayed AIDS progression and resistance to infection ( 32 , 88 – 90 ). NK cells expressing KIR3DS1 are licensed by this receptor to activate in response to HLA-Bw4 expressed on target cells and they show an improved capacity of both cytotoxicity and IFN-γ production, apparently by HLA-Bw4 recognition in a peptide-dependent manner ( 91 ).…”

Section: Nk Cell Repertoire Is Associated With Hiv Progression and Rementioning

confidence: 99%

NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies

2018

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NK cells play a key role in immune response against HIV infection. These cells can destroy infected cells and contribute to adequate and strong adaptive immune responses, by acting on dendritic, T, B, and even epithelial cells. Increased NK cell activity reflected by higher cytotoxic capacity, IFN-γ and chemokines (CCL3, CCL4, and CCL5) production, has been associated with resistance to HIV infection and delayed AIDS progression, demonstrating the importance of these cells in the antiviral response. Recently, a subpopulation of NK cells with adaptive characteristics has been described and associated with lower HIV viremia and control of infection. These evidences, together with some degree of protection shown in vaccine trials based on boosting NK cell activity, suggest that these cells can be a feasible option for new treatment and vaccination strategies to overcome limitations that, classical vaccination approaches, might have for this virus. This review is focus on the NK cells role during the immune response against HIV, including all the effector mechanisms associated to these cells; in addition, changes including phenotypic, functional and frequency modifications during HIV infection will be pointed, highlighting opportunities to vaccine development based in NK cells effector functions.

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Section: Nk Cell Repertoire Is Associated With Hiv Progression and Rementioning

confidence: 99%

NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies

2018

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“…Increasing evidence suggests that specific NK cell features can also confer protection from HIV acquisition. Genetic studies revealed that the presence of specific KIR/HLA combinations may contribute to protection of HESN from HIV infection via intravenous or sexual routes [20][21][22][23][24][25][26]. Additionally, a less diverse and more flexible NK cell receptor repertoire has been associated with lower risk of acquiring HIV in sexually exposed Kenyan women [27].…”

Section: Introductionmentioning

confidence: 99%

Natural killer cell phenotype is altered in HIV-exposed seronegative women

et al. 2020

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Highly exposed seronegative (HESN) individuals present a unique setting to study mechanisms of protection against HIV acquisition. As natural killer (NK) cell activation and function have been implicated as a correlate of protection in HESN individuals, we sought to better understand the features of NK cells that may confer protection. We used mass cytometry to phenotypically profile NK cells from a cohort of Beninese sex workers and healthy controls. We found that NK cells from HESN women had increased expression of NKG2A, NKp30 and LILRB1, as well as the Fc receptor CD16, and decreased expression of DNAM-1, CD94, Siglec-7, and NKp44. Using functional assessments of NK cells from healthy donors against autologous HIV-infected CD4 + T cells, we observed that NKp30 + and Siglec-7 + cells had improved functional activity. Further, we found that NK cells from HESN women trended towards increased antibody-dependent cellular cytotoxicity (ADCC) activity; this activity correlated with increased CD16 expression. Overall, we identify features of NK cells in HESN women that may contribute to protection from HIV infection. Follow up studies with larger cohorts are warranted to confirm these findings.

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“…S1 details the KIR polymorphisms for the gene content analysis and S2 outlines the KIR3DL1/S1 genotypes (HIVI and HESN) for the genotype analysis. The number of articles included seven with Caucasian subjects (1,313 cases /485 controls)[40–44, 46, 47]; two Asians (256 cases /151 controls) [38, 39] and four Africans (588 cases /599 controls) [34–37]. Non-normal distribution of the CB scores (SW, P = 0.04) indicated high methodological quality of the included articles (median: 7, IQR: 6–8).…”

Section: Resultsmentioning

confidence: 99%

Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis

Chaisri¹,

Pabalan²,

Tabunhan³

et al. 2019

PLoS ONE

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BackgroundGenetic involvement of Killer Immunoglobulin-like Receptor (KIR) polymorphisms and Human Immunodeficiency Virus (HIV)-exposed seronegative (HESN) compared to HIV-infected (HIVI) individuals has been reported. However, inconsistency of the outcomes reduces precision of the estimates. A meta-analysis was applied to obtain more precise estimates of association.MethodsA multi-database literature search yielded thirteen case-control studies. Risks were expressed as odds ratios (ORs) and 95% confidence intervals (CIs) with significance set at a two-tailed P-value of ≤ 0.05. We used two levels of analyses: (1) gene content that included 13 KIR polymorphisms (2DL1-3, 2DL5A, 2DL5B, 2DS1-3, 2DS4F, 2DS4D, 2DS5, 3DL1 and 3DS1); and (2) 3DL1/S1 genotypes. Subgroup analysis was ethnicity-based (Caucasians, Asians and Africans). Outlier treatment was applied to heterogeneous effects which dichotomized the outcomes into pre-outlier (PRO) and post-outlier (PSO). Multiple comparisons were addressed with the Bonferroni correction.ResultsWe generated 52 and 18 comparisons from gene content and genotype analyses, respectively. Of the 70 comparisons, 13 yielded significant outcomes, two (indicating reduced risk) of which survived the Bonferroni correction (Pc). These protective effects pointed to the Caucasian subgroup in 2DL3 (OR 0.19, 95% CI 0.09, 0.40, Pc < 10−3) and 3DS1S1 (OR 0.37, 95% CI 0.24, 0.56, Pc < 10−3). These two PSO outcomes yielded effects of increased magnitude and precision, as well as raised significance and deemed robust by sensitivity analysis. Of the two, the 2DL3 effect was improved with a test of interaction (Pc interaction < 10−4).ConclusionMultiple meta-analytical treatments presented strong evidence of the protective effect (up to 81%) of the KIR polymorphisms (2DL3 and 3DS1S1) among Caucasians. The Asian and African outcomes were inconclusive due to the low number of studies.

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HIV exposed seronegative (HESN) compared to HIV infected individuals have higher frequencies of telomeric Killer Immunoglobulin-like Receptor (KIR) B motifs; Contribution of KIR B motif encoded genes to NK cell responsiveness

Cited by 15 publications

References 64 publications

NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies

NK Cells in HIV-1 Infection: From Basic Science to Vaccine Strategies

Natural killer cell phenotype is altered in HIV-exposed seronegative women

Effects of the killer immunoglobulin–like receptor (KIR) polymorphisms on HIV acquisition: A meta-analysis

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