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Correlates of Immune Protection against HIV Infection

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A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (20 April 2022) | Viewed by 28182

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Special Issue Editors

Prof. Dr. Nicole F. Bernard

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Guest Editor

Department of Medicine, Division of Experimental Medicine, McGill University Health Centre (MUHC), Montreal, QC, Canada
Interests: My research focus is the study of the immune correlates of protection against HIV infection and slow disease progression in those already infected.

Prof. Dr. Keith Fowke

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Guest Editor

Departments of Medical Microbiology and Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Interests: HIV immunology; HIV-exposed uninfected; immune quiescence; inflammation

Dr. Julie Lajoie

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Guest Editor

Departments of Medical Microbiology and Community Health Sciences, University of Manitoba, Winnipeg, MB, Canada
Interests: HIV immunology; HIV-exposed uninfected; immune quiescence; inflammation

Special Issue Information

Dear Colleagues,

There have been important advancements in preventing HIV infection through interventions such as treatment as prevention (TASP), pre-exposure prophylaxis (PrEP), circumcision and condom use. Despite this, there were 1.7 million new HIV infections reported globally in 2019. It is notable that some individuals remain HIV uninfected despite being highly exposed to this virus. Such HIV Exposed SeoroNegative (HESN) people can be found among commercial sex workers, injection drug users, men who have sex with men and HIV discordant heterosexual and homosexual couples. Children of treatment naïve HIV-infected mothers who remain HIV seronegative are also a model for HIV exposure. A well accepted mechanism for resistance to HIV infection is homozygosity for the Δ32CCR5 genotype that prevents the CCR5 co-receptor for HIV entry from being expressed on cells otherwise susceptible to HIV infection. However, carriage of this genotype accounts for only a fraction of people considered to be HESN. The mechanisms underlying the ability of HESNs to remain uninfected may vary from one group to another and depend on the route of exposure. Understanding the mechanisms underlying why some people appear to be resistant to HIV has the potential to inform the development of novel preventative strategies against HIV infection that can be added to the arsenal of protective interventions. Understanding the mechanisms of natural models of resistance to HIV is of interest to other areas of infectious diseases, such as COVID-19.

This Special Issue of Viruses is focused on describing Immune Correlates of Protection against HIV Infection.

This Special Issue will bring together cutting-edge research in the basic and clinical sciences, epidemiology and the behavioral and social sciences. The aim of this Special Issue is to collate evidence-based manuscripts on relevant topics in the field. Research articles, clinical studies, meta-analyses, and reviews are all welcome.

Prof. Dr. Nicole F. Bernard
Prof. Dr. Keith Fowke
Dr. Julie Lajoie
Guest Editors

Manuscript Submission Information

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

HESN
immune quiescence
innate immunity
natural resistance
adaptive immunity
mucosal immunology
neutralizing antibodies
T cells
NK cells

Published Papers (7 papers)

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Research

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20 pages, 2863 KiB

Open AccessArticle

Transient Increases in Inflammation and Proapoptotic Potential Are Associated with the HESN Phenotype Observed in a Subgroup of Kenyan Female Sex Workers

by Marcel Gluchowski, Xiaoqiong Yu, Bernard Abrenica, Samantha Yao, Joshua Kimani, Renée N. Douville, Terry Blake Ball and Ruey-Chyi Su

Viruses 2022, 14(3), 471; https://0-doi-org.brum.beds.ac.uk/10.3390/v14030471 - 25 Feb 2022

Cited by 1 | Viewed by 1833

Abstract

Interferon (IFN) -stimulated genes (ISGs) are critical effectors of IFN response to viral infection, but whether ISG expression is a correlate of protection against HIV infection remains elusive. A well-characterized subcohort of Kenyan female sex workers, who, despite being repeatedly exposed to HIV-1 remain seronegative (HESN), exhibit reduced baseline systemic and mucosal immune activation. This study tested the hypothesis that regulation of ISGs in the cells of HESN potentiates a robust antiviral response against HIV. Transcriptional profile of a panel of ISGs with antiviral function in PBMC and isolated CD4+ T cells from HESN and non-HESN sex worker controls were defined following exogenous IFN-stimulation using relative RT-qPCR. This study identified a unique profile of proinflammatory and proapoptotic ISGs with robust but transient responses to exogenous IFN-γ and IFN-α2 in HESN cells. In contrast, the non-HESN cells had a strong and prolonged proinflammatory ISG profile at baseline and following IFN challenge. Potential mechanisms may include augmented bystander apoptosis due to increased TRAIL expression (16-fold), in non-HESN cells. The study also identified two negative regulators of ISG induction associated with the HESN phenotype. Robust upregulation of SOCS-1 and IRF-1, in addition to HDM2, could contribute to the strict regulation of proinflammatory and proapoptotic ISGs in HESN cells. As reducing IRF-1 in the non-HESN cells resulted in the identified HESN ISG profile, and decreased HIV susceptibility, the unique HESN ISG profile could be a correlate of protection against HIV infection. Full article

(This article belongs to the Special Issue Correlates of Immune Protection against HIV Infection)

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20 pages, 4749 KiB

Open AccessArticle

Monocyte Gene and Molecular Expression Profiles Suggest Distinct Effector and Regulatory Functions in Beninese HIV Highly Exposed Seronegative Female Commercial Sex Workers

by Laurence Blondin-Ladrie, Lyvia Fourcade, Alessandro Modica, Matheus Aranguren, Nicolas de Montigny, Annie-Claude Labbé, Michel Alary, Fernand Guédou, Johanne Poudrier and Michel Roger

Viruses 2022, 14(2), 361; https://0-doi-org.brum.beds.ac.uk/10.3390/v14020361 - 10 Feb 2022

Cited by 2 | Viewed by 2256

Abstract

We have previously reported that the female genital tract (FGT) of Beninese HIV highly-exposed seronegative (HESN) commercial sex workers (CSWs), presented elevated frequencies of a myeloid HLA-DR+CD14+CD11c+ population presenting “tolerogenic” monocyte derived dendritic cells (MoDC) features. In order to assess whether a differential profile of monocytes may be involved in the generation of these genital MoDCs, we have herein characterized the blood monocyte compartment of Beninese HESNs (HIV-uninfected ≥ 10 years CSWs) and relevant controls (HIV-uninfected 2.5–5 years CSWs herein termed “early HESNs”), HIV-infected CSWs, and low-risk HIV-uninfected women from the general population. Transcriptomic analyses by RNA-Seq of total sorted blood monocytes demonstrate that in comparison to the control groups, HESNs present increased expression levels of FCGR2C, FCAR, ITGAX, ITGAM, CR2, CD68, and CD163 genes, associated with effector functions. Moreover, we found increased expression levels of genes associated with protection/control against SHIV/HIV such as CCL3, CCL4, CCL5, BHLHE40, and TNFSF13, as well as with immune regulation such as IL-10, Ahr, CD83, and the orphan nuclear receptor (NR)4A1, NR4A2, and NR4A3. Through multicolor flow cytometry analyses, we noticed that the frequencies of intermediate and non-classical monocyte populations tended to be elevated in the blood of HESNs, and exhibited increased expression levels of effector CD16, CD11c, CD11b, as well as regulatory HLA-G, IL-10, and IFN-α markers when compared to HIV-uninfected women and/or HIV-infected CSWs. This profile is compatible with that previously reported in the FGT of HESNs, and likely confers an enormous advantage in their resistance to HIV infection. Full article

(This article belongs to the Special Issue Correlates of Immune Protection against HIV Infection)

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14 pages, 2028 KiB

Open AccessArticle

The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion

by Christophe Vanpouille, Gökçe Günaydın, Mattias Jangard, Mario Clerici, Leonid Margolis, Kristina Broliden and Andrea Introini

Viruses 2021, 13(11), 2303; https://0-doi-org.brum.beds.ac.uk/10.3390/v13112303 - 18 Nov 2021

Cited by 1 | Viewed by 2059

Abstract

The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the changes occurring in the female genital mucosa and blood. However, one of the main sites of HIV-1 pathogenesis is lymphoid organs. To investigate the immunoregulatory effect of medroxyprogesterone acetate (MPA) at this site, human tonsillar tissue explants were infected ex vivo with either a CCR5 (BaL) or CXCR4 (LAI) HIV-1 variant and the release of p24_gag and cytokines was measured in culture supernatant. The response to MPA was compared with that elicited by treatment with progesterone (P4) and dexamethasone (DEX), which selectively binds the glucocorticoid receptor, in donor-matched explant cultures. MPA treatment reduced the replication of both tested HIV-1 strains as well as the production of the mediators of inflammation IL-1β, IL-17A and CCL5, but not CCL20, in a similar way to DEX, whereas P4 had no effect on HIV-1 replication. The magnitude of both MPA and DEX-mediated responses was proportional to the length of exposure and/or administered dose. Blockage of the progesterone and glucocorticoid receptors with mifepristone abolished all observed changes in HIV-1 and cytokine production, and was associated with increased IL-22 levels in HIV-infected explants. Our data indicate that elevated doses of MPA may affect the immune responses in lymphoid tissue in a glucocorticoid-like fashion with an immediate impact on local HIV-1 replication. Full article

(This article belongs to the Special Issue Correlates of Immune Protection against HIV Infection)

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Review

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13 pages, 409 KiB

Open AccessReview

Natural Immunity against HIV-1: Progression of Understanding after Association Studies

by Ma Luo

Viruses 2022, 14(6), 1243; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061243 - 08 Jun 2022

Cited by 2 | Viewed by 6497 | Correction

Abstract

Natural immunity against HIV has been observed in many individuals in the world. Among them, a group of female sex workers enrolled in the Pumwani sex worker cohort remained HIV uninfected for more than 30 years despite high-risk sex work. Many studies have been carried out to understand this natural immunity to HIV in the hope to develop effective vaccines and preventions. This review focuses on two such examples. These studies started from identifying immunogenetic or genetic associations with resistance to HIV acquisition, and followed up with an in-depth investigation to understand the biological relevance of the correlations of protection, and to develop and test novel vaccines and preventions. Full article

(This article belongs to the Special Issue Correlates of Immune Protection against HIV Infection)

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16 pages, 823 KiB

Open AccessReview

The Penis, the Vagina and HIV Risk: Key Differences (Aside from the Obvious)

by Rupert Kaul, Cindy M. Liu, Daniel E. Park, Ronald M. Galiwango, Aaron A. R. Tobian and Jessica L. Prodger

Viruses 2022, 14(6), 1164; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061164 - 27 May 2022

Cited by 4 | Viewed by 11202

Abstract

Globally, most Human Immunodeficiency Virus type 1 (HIV) transmission occurs through vaginal–penile sex (heterosexual transmission). The local immune environment at the site of HIV exposure is an important determinant of whether exposure during sex will lead to productive infection, and the vaginal and penile immune milieus are each critically shaped by the local microbiome. However, there are key differences in the microbial drivers of inflammation and immune quiescence at these tissue sites. In both, a high abundance of anaerobic taxa (e.g., Prevotella) is associated with an increased local density of HIV target cells and an increased risk of acquiring HIV through sex. However, the taxa that have been associated to date with increased risk in the vagina and penis are not identical. Just as importantly, the microbiota associated with comparatively less inflammation and HIV risk—i.e., the optimal microbiota—are very different at the two sites. In the vagina, Lactobacillus spp. are immunoregulatory and may protect against HIV acquisition, whereas on the penis, “skin type” flora such as Corynebacterium are associated with reduced inflammation. Compared to its vaginal counterpart, much less is known about the dynamics of the penile microbiome, the ability of clinical interventions to alter the penile microbiome, or the impact of natural/induced microbiome alterations on penile immunology and HIV risk. Full article

(This article belongs to the Special Issue Correlates of Immune Protection against HIV Infection)

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20 pages, 1897 KiB

Open AccessReview

NK Cells in Protection from HIV Infection

by Nicole F. Bernard, Khlood Alsulami, Erik Pavey and Franck P. Dupuy

Viruses 2022, 14(6), 1143; https://0-doi-org.brum.beds.ac.uk/10.3390/v14061143 - 25 May 2022

Cited by 3 | Viewed by 2768

Abstract

Some people, known as HIV-exposed seronegative (HESN) individuals, remain uninfected despite high levels of exposure to HIV. Understanding the mechanisms underlying their apparent resistance to HIV infection may inform strategies designed to protect against HIV infection. Natural Killer (NK) cells are innate immune cells whose activation state depends on the integration of activating and inhibitory signals arising from cell surface receptors interacting with their ligands on neighboring cells. Inhibitory NK cell receptors use a subset of major histocompatibility (MHC) class I antigens as ligands. This interaction educates NK cells, priming them to respond to cells with reduced MHC class I antigen expression levels as occurs on HIV-infected cells. NK cells can interact with both autologous HIV-infected cells and allogeneic cells bearing MHC antigens seen as non self by educated NK cells. NK cells are rapidly activated upon interacting with HIV-infected or allogenic cells to elicit anti-viral activity that blocks HIV spread to new target cells, suppresses HIV replication, and kills HIV-infected cells before HIV reservoirs can be seeded and infection can be established. In this manuscript, we will review the epidemiological and functional evidence for a role for NK cells in protection from HIV infection. Full article

(This article belongs to the Special Issue Correlates of Immune Protection against HIV Infection)

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