Apoptosis as a mechanism of natural resistance to HIV-1 infection in an exposed but uninfected population

Velilla, Paula A.; Hoyos, Álvaro Turriago; Rojas, Mauricio; Patiño, Pablo Javier; Vélez, Lázaro A.; Rugeles, Marı́a Teresa

doi:10.1016/j.jcv.2004.08.018

Cited by 12 publications

(6 citation statements)

References 47 publications

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“…We found that peripheral blood monocytes in the ESNs group had a greater predisposition to undergo spontaneous apoptosis as well as apoptosis induced by HIV infection in vitro , compared to monocytes from HCs at low risk of HIV infection. This suggests that monocytes could play an important role in the control of HIV infection by undergoing apoptosis [5]. …”

Section: Immune Response During Hiv-1 Exposurementioning

confidence: 99%

“…Certain reports indicate that apoptosis of target cells [5], increased production of interferon gamma (IFN-γ) by natural killer (NK) cells [6] and positive regulation of costimulatory molecules [7] are factors associated with resistance. The humoral response contributes significantly to resistance to HIV infection through the production of anti- HIV IgA in mucosal [8] and finally, several soluble factors such as RNases, chemokines, cytokines and cationic proteins are involved in blocking HIV infection in ESNs or in decreasing the time required to disease progression in LTNPs individuals [9].…”

Section: Introductionmentioning

confidence: 99%

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Genetic and Immunological Factors Involved in Natural Resistance to HIV-1 Infection

Vanegas

Zapata²,

Rugeles

2011

TOVJ

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Infection with Human immunodeficiency virus type-1 (HIV-1) induces severe alterations of the immune system leading to an increased susceptibility to opportunistic infections and malignancies. However, exposure to the virus does not always results in infection. Indeed, there exist individuals who have been repeatedly exposed to HIV-1 but do not exhibit clinical or serological evidence of infection, known as exposed seronegative individuals. Many studies have focused on the different mechanisms involved in natural resistance to HIV-1 infection, and have reported several factors associated with this phenomenon, including the presence of genetic polymorphisms in the viral coreceptors, innate and adaptive immune cells with particular phenotypic and functional features, and molecules such as antibodies and soluble factors that play an important role in defense against infection by HIV-1. The study of these factors could be the key for controlling this viral infection. This review summarizes the main mechanisms involved in resistance to HIV-1 infection.

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Section: Immune Response During Hiv-1 Exposurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genetic and Immunological Factors Involved in Natural Resistance to HIV-1 Infection

Vanegas

Zapata²,

Rugeles

2011

TOVJ

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“…Some genetic and immunological mechanisms have been associated with the resistant phenotype as follows: (i) genetic polymorphisms in the required co-receptors for viral entry, such as CCR5 or CCR2 ( 5 , 6 ); (ii) increased production of the co-receptor ligands MIP-1α/β, RANTES or SDF-1; (iii) the presence of antibodies blocking viral co-receptors ( 7 ); (iv) the expression of different microRNAs induced by the viral exposure ( 8 , 9 ) that may modulate the innate immune system or interfere directly with viral mRNAs blocking the infection ( 10 ); (v) induction of spontaneous apoptosis of target cells ( 6 , 11 ); (vi) production of soluble factors with antiviral activity, such as TRIM5α, APOBEC-3G, SAMHD-1, serpina1, elafin, Human neutrophil peptide, beta-defensins, and LL-37 ( 12 – 14 ), other proteins implicated in host defense and bacterial binding, such as bPRP2, Histatin-3, Lysozyme C, and SLPI ( 15 ), and the presence of non-cationic proteins in genital secretions with HIV-1 neutralizing activity ( 16 ); (vii) high activity of natural killer cells ( 17 , 18 ) and dendritic cells (DC) ( 19 ); (viii) high levels of neutralizing IgA antibodies ( 18 , 20 ), which are even associated with protection in vaccine clinical trials, as they could prevent HIV mucosal transcytosis ( 21 ); (ix) expression of the alleles HLA-B57 and -B27 that present immunodominant peptides ( 6 ); and (x) effective and polyfunctional profile of HIV-specific CD4 + and CD8 + T cell responses ( 22 , 23 ).…”

Section: Introductionmentioning

confidence: 99%

Role of Different Subpopulations of CD8+ T Cells during HIV Exposure and Infection

2017

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During HIV infection, specific responses exhibited by CD8+ T cells are crucial to establish an early, effective, and sustained viral control, preventing severe immune alterations and organ dysfunction. Several CD8+ T cells subsets have been identified, exhibiting differences in terms of activation, functional profile, and ability to limit HIV replication. Some of the most important CD8+ T cells subsets associated with viral control, production of potent antiviral molecules, and strong polyfunctional responses include Th1-like cytokine pattern and Tc17 cells. In addition, the expression of specific activation markers has been also associated with a more effective response of CD8+ T cells, as evidenced in HLA-DR+ CD38− cells. CD8+ T cells in both, peripheral blood and gut mucosa, are particularly important in individuals with a resistant phenotype, including HIV-exposed seronegative individuals (HESNs), long-term non-progressors (LTNPs) and HIV-controllers. Although the role of CD8+ T cells has been extensively explored in the context of an established HIV-1 infection, the presence of HIV-specific cells with effector abilities and a defined functional profile in HESNs, remain poorly understood. Here, we reviewed studies carried out on different subpopulations of CD8+ T cells in relation with natural resistance to HIV infection and progression.

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“…Despite the rapid spread of this virus, some individuals, known as exposed seronegatives (ESN), have an apparent resistance to HIV-1 infection despite multiple and repeated exposures [2]. Numerous factors have been proposed as potentially protective mechanisms including the rapid development of adaptive cellular [3] and humoral defenses [4], as well as certain elements of the innate immune response [5-7]. These findings have not been consistently reproduced from one study to another and among persons at high risk for HIV infection by the parenteral route [8]; only a 32 base pair deletion in the CCR5 gene was demonstrably associated with protection against infection [9].…”

Section: Introductionmentioning

confidence: 99%

Increased Levels of Human Beta-Defensins mRNA in Sexually HIV-1 Exposed But Uninfected Individuals

Zapata¹,

Rodrı́guez²,

Weber³

et al. 2008

CHR

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Protection against HIV-1 infection in exposed seronegative (ESN) individuals likely involves natural resistance mechanisms that have not been fully elucidated. Human beta defensins (HBD) are antimicrobial peptides found primarily in mucosae, the main ports of HIV entry. HBD-2 and 3 mRNA are induced by HIV-1 in human oral epithelial cells and exhibit strong anti-HIV-1 activity; in addition, polymorphisms in the DEFB1 gene, which encodes HBD-1, have been associated with resistance/susceptibility to different infections, including HIV-1. Here, we have assessed the association of HBD expression with the ESN phenotype. Peripheral blood and vaginal/endocervical and oral mucosal samples were taken from 47 ESN, 44 seropositive (SP) and 39 healthy controls (HC). HBD-1, 2 and 3 mRNA copy numbers were quantified by real time RT-PCR and A692G/G1654A/A1836G polymorphisms in the DEFB1 gene were detected by restriction fragment length polymorphisms and confirmed by nucleotide sequencing. ESN expressed significantly greater mRNA copy numbers of HBD-2 and 3 in oral mucosa than HC; p=0.0002 and p=0.007, respectively. mRNA copy numbers of HBD-1, 2 and 3 in vaginal/endocervical mucosa from ESN and HC were similar. Homozygosity for the A692G polymorphism was significantly more frequent in ESN (0.39) than in SP (0.05) (p=0.0002). In summary, ESN exhibited enhanced mucosal expression of the innate defense genes HBD-2 and 3; however, additional studies are required to verify these results and the potential association of the A692G polymorphism to the relative resistance of ESN to HIV-1 infection.

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Apoptosis as a mechanism of natural resistance to HIV-1 infection in an exposed but uninfected population

Cited by 12 publications

References 47 publications

Genetic and Immunological Factors Involved in Natural Resistance to HIV-1 Infection

Genetic and Immunological Factors Involved in Natural Resistance to HIV-1 Infection

Role of Different Subpopulations of CD8+ T Cells during HIV Exposure and Infection

Increased Levels of Human Beta-Defensins mRNA in Sexually HIV-1 Exposed But Uninfected Individuals

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