Variation sites at the HLA-G 3’ untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell

Medeiros, Fernanda; Martins, Albert Eduardo Silva; Gomes, Rachel Novaes; Oliveira, Stefan Vilges de; Welkovic, Stefan; Maruza, Magda; Menezes, Maria Luiza Bezerra; Ximenes, Ricardo Arraes de Alencar; Diniz, George Tadeu Nunes; Donadi, Eduardo Antônio; Lucena‐Silva, Norma

doi:10.1371/journal.pone.0204679

Cited by 12 publications

(11 citation statements)

References 51 publications

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“…Moreover, some have focused on the association between HLA-G 3 ′ UTR polymorphisms and HPV infection among HIV-positive women who have a higher risk of developing HPV co-infection. The combination of the +3142CX (CC or CG) and +3187AA genotypes conferred the highest risk of HPV-induced aneuploidy in cervical cells among Brazilian women with HIV/HPV co-infections (94).A SNP (rs1633038) in the 3 ′ UTR of the HLA-G gene was significantly related to higher HPV clearance rates among African-Americans with HIV/HPV co-infection, but this association was not observed in Hispanics or European-Americans (95).…”

Section: Hla-g Polymorphisms In the Context Of Hpv Infectionsmentioning

confidence: 96%

“…Accumulating evidence has supported the concept that HLA-G polymorphisms are genetic susceptibility and/or protection-relevant factors for cervical HPV infections and viral persistence (89)(90)(91)(92)(93)(94)(95)(96)(97)(98)(99)(100)(101). Many studies have primarily focused on polymorphisms in the 3 ′ UTR of the HLA-G gene (89-95), while few have assessed its promoter region (96).…”

Section: Hla-g Polymorphisms In the Context Of Hpv Infectionsmentioning

confidence: 99%

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The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

Xu¹,

Yan²,

Lin³

2020

Front. Immunol.

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Human leukocyte antigen (HLA)-G, a non-classical HLA-class I molecule, has a low polymorphism frequency, restricted tissue distribution and immunoinhibitory property. HLA-G expression in tumor cells and cells chronically infected with virus may enable them to escape from host immune surveillance. It is well-known that the HLA-G molecule is a novel biomarker and potential therapeutic target that is relevant in various types of cancers, but its role in cervical cancer has not been fully explored. In this review, we aim to summarize and discuss the immunologic role of the HLA-G molecule in the context of HPV infections and the process of cervical cancer carcinogenesis. A better understanding of the potential impact of HLA-G on the clinical course of persistent HPV infections, cervical epithelial cell transformation, tumor growth, recurrence and metastasis is needed to identify a novel diagnostic/prognostic biomarker for cervical cancer, which is critical for cervical cancer risk screening. In addition, it is also necessary to identify HLA-G-driven immune mechanisms involved in the interactions between host and virus to explore novel immunotherapy strategies that target HLA-G/immunoglobulin-like transcript (ILT) immune checkpoints.

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Section: Hla-g Polymorphisms In the Context Of Hpv Infectionsmentioning

confidence: 96%

Section: Hla-g Polymorphisms In the Context Of Hpv Infectionsmentioning

confidence: 99%

The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

Xu¹,

Yan²,

Lin³

2020

Front. Immunol.

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“…Moreover, the +3142G and +3187A alleles were significantly associated with predisposition to HIV infection, irrespective of the presence or not of HIV/HPV co‐infection. Finally, the +3187G allele and the +3187GG genotype significantly predominated among healthy women (Medeiros et al., 2018).…”

Section: Hla‐g and Diseasementioning

confidence: 99%

“…Recent data revealed that polymorphisms located in the 3′-UTR region of the gene played a role in HIV susceptibility. In a recent analysis of HLA-G polymorphisms in a cohort of HIV-infected woman, co-infected or not with HPV (Medeiros et al, 2018), it was found that the +3142G allele and +3142GG genotype were significantly overrepresented in all HIV-infected women. Moreover, the +3142G…”

Section: Chronic Viral Infectionsmentioning

confidence: 99%

HLA‐G: Function, polymorphisms and pathology

Arnaiz‐Villena

Juárez

Suárez-Trujillo

et al. 2020

Int J Immunogenetics

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HLA‐G immune modulatory genes and molecules are presently being studied by a widespread number of research groups. In the present study, we do not aim to be exhaustive since the number of manuscripts published every year is overwhelming. Instead, our aim is pointing out facts about HLA‐G function, polymorphism and pathology that have been confirmed by several different researchers, together with exposing aspects that may have been overlooked or not sufficiently remarked in this productive field of study. On the other hand, we question whether performing mainly studies on HLA‐G and disease associations is going to give a clear answer in the future, since 40 years of study of classical HLA molecules association with disease has still given no definite answer on this issue.

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“…primarily reflect the severity of inflammation associated with HPV infection (Yang et al, 2013), whereas the expression at the epithelium strongly indicates the role of PD-1 on the progression of the cervical lesions (Yang et al, 2017;Chang et al, 2018;Medeiros et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 (PDCD1) rs36084323 A Allele in a Dominant Model

Silva

Medeiros

Silva

et al. 2021

Front. Cell. Infect. Microbiol.

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The high-risk oncogenic human papillomavirus (HPV) has developed mechanisms for evasion of the immune system, favoring the persistence of the infection. The chronic inflammation further contributes to the progression of tissue injury to cervical cancer. The programmed cell death protein (PD-1) after contacting with its ligands (PD-L1 and PD-L2) exerts an inhibitory effect on the cellular immune response, maintaining the balance between activation, tolerance, and immune cell-dependent lesion. We evaluated 295 patients exhibiting or not HPV infection, stratified according to the location (injured and adjacent non-injured areas) and severity of the lesion (benign, pre-malignant lesions). Additionally, we investigated the role of the promoter region PDCD1 -606G>A polymorphism (rs36084323) on the studied variables. PD-1 and PDCD1 expression were evaluated by immunohistochemistry and qPCR, respectively, and the PDCD1 polymorphism was evaluated by nucleotide sequencing. Irrespective of the severity of the lesion, PD-1 levels were increased compared to adjacent uninjured areas. Additionally, in cervical intraepithelial neoplasia (CIN) I, the presence of HPV was associated with increased (P = 0.0649), whereas in CIN III was associated with decreased (P = 0.0148) PD-1 levels, compared to the uninjured area in absence of HPV infection. The PDCD1 -606A allele was rare in our population (8.7%) and was not associated with the risk for development of HPV infection, cytological and histological features, and aneuploidy. In contrast, irrespective of the severity of the lesion, patients exhibiting the mutant PDCD1 -606A allele at single or double doses exhibited increased protein and gene expression when compared to the PDCD1 -606GG wild type genotype. Besides, the presence of HPV was associated with the decrease in PDCD1 expression and PD-1 levels in carriers of the -606 A allele presenting severe lesions, suggesting that other mediators induced during the HPV infection progression may play an additional role. This study showed that increased PD-1 levels are influenced by the -606G>A nucleotide variation, particularly in low-grade lesions, in which the A allele favors increased PDCD1 expression, contributing to HPV immune system evasion, and in the high-grade lesion, by decreasing tissue PD-1 levels.

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Variation sites at the HLA-G 3’ untranslated region confer differential susceptibility to HIV/HPV co-infection and aneuploidy in cervical cell

Cited by 12 publications

References 51 publications

The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

The Role of HLA-G in Human Papillomavirus Infections and Cervical Carcinogenesis

HLA‐G: Function, polymorphisms and pathology

Increased PD-1 Level in Severe Cervical Injury Is Associated With the Rare Programmed Cell Death 1 (PDCD1) rs36084323 A Allele in a Dominant Model

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