Association of polymorphisms in NFκB1 promoter and NFκBIA gene with the development of antibodies against HHV-8 in HIV-infected individuals

Gonçales, Juliana Prado; Júnior, José Valter Joaquim Silva; Lopes, Thaísa Regina Rocha; Tozetto‐Mendoza, Tânia Regina; D, Guimaraes; Morais, Viviane Martha Santos de; Coêlho, Maria Rosângela Cunha Duarte

doi:10.1016/j.virol.2019.07.011

Cited by 3 publications

(7 citation statements)

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“…The limited number of retrieved studies and the low-level of evidence of the retrieved studies [ 42 , 43 ], together with the low number of recent publications investigating this topic suggests that this potentially controversial topic has not been studied in depth from a broad, multidisciplinary perspective. Scientific interest in recent years has focused mainly on describing the viral oncogenic role through mechanistic studies [ 44 , 45 , 46 , 47 , 48 ] and relatively little attention has been paid to the analysis of factors influencing clonal growth in KS. However, the identification of such underlying mechanisms and subsequent definitions could lead to improvements in the clinical management of KS patients.…”

Section: Discussionmentioning

confidence: 99%

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review

Ruiz

Armon

Watanabe

et al. 2022

Cancers

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Background: It remains uncertain whether Kaposi sarcoma (KS) is a true neoplasm, in that it regresses after removal of the stimulus to growth (as HHV8) when immunosuppression is reduced. We aimed to summarize the available evidence on somatic mutations and clonality within KS to assess whether KS is a neoplasm or not. Methods: Medline and Web of Science were searched until September 2020 for articles on clonality or mutation in KS. Search strings were supervised by expert librarians, and two researchers independently performed study selection and data extraction. An adapted version of the QUADAS2 tool was used for methodological quality appraisal. Results: Of 3077 identified records, 20 publications reported on relevant outcomes and were eligible for qualitative synthesis. Five studies reported on clonality, 10 studies reported on various mutations, and 5 studies reported on chromosomal aberrations in KS. All studies were descriptive and were judged to have a high risk of bias. There was considerable heterogeneity of results with respect to clonality, mutation and cytogenetic abnormalities as well as in terms of types of lesions and patient characteristics. Conclusions: While KS certainly produces tumours, the knowledge is currently insufficient to determine whether KS is a clonal neoplasm (sarcoma), or simply an aggressive reactive virus-driven lesion.

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Section: Discussionmentioning

confidence: 99%

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review

Ruiz

Armon

Watanabe

et al. 2022

Cancers

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“…MBL2 haplotypes (based on combinations of two promoter region genotypes (−550 H/L and −221 Y/X) and a structural region genotype (exon 1 A/O)) associated with intermediate expression of MBL, an innate immune system protein, were found to be associated with lower CD4 count in HIV and KSHV co‐infected patients compared to patients with only HIV infection 47 . Additionally, polymorphisms in the NFκB1 promoter (NG_050628.1:g.4670_4673ATTG[1], reference SNP (rs)28 362 491) and the 3′ UTR region of the NFκB1 inhibitor alpha (NM_020529.3:NFκBIA c.*126G>A, rs696) were found to be associated with the presence of antibodies to KSHV lytic antigens 46 . Natural killer (NK) cell activation is important in the immune response to viruses and proposed to be protective against KSHV infection 50,68 .…”

Section: Candidate Susceptibility Genes—current Knowledgementioning

confidence: 99%

“…Lagging diagnostics, particularly of KSHV‐associated pathologies other than KS, are an issue. Even diagnosis of KSHV infection (by antibody response using various serological assays 23,46,58 or viral load in peripheral blood leukocytes 45 ) or KS (by clinical examination with or without indicated biopsy and histological confirmation, 50,52,58 with or without investigations for visceral KS and with or without tumour staging) is heterogeneously performed or not reported at all. For example, KSHV seropositivity may not be a consistently defined phenotype between studies, as Newton et al 23 noted disparity in KSHV seroprevalence estimates between their study and those previously reported due to the sensitivity of different serological assays (peptide based EIAs, protein ELISA and immunofluorescent assays).…”

Section: Limitations Of Current Reports and Genetic Association Studiesmentioning

confidence: 99%

“…Thus far, immune-modulatory genes have been the focus of investigations of candidate susceptibility genes. In particular, published studies have reported significant associations of KSHV infection or its associated pathologies with genetic polymorphism in genes encoding interleukins IL6, IL8 and IL13, [41][42][43][44] vascular endothelial growth factor (VEGF), 45 nuclear factor kappa B (NFκB), 46 mannose-binding lectin (MBL)-2, 47 Fc gamma receptors (FcγR), 48 HLA killer cell immunoglobulin-like receptors (KIR) 49,50 and their HLA ligands and linked genes [50][51][52][53][54][55][56] and homologues of human genes pirated by KSHV, namely cyclin D1 (CCND1), IL6, C-C chemokine ligand 2 (CCL2) and FADD-like apoptosis regulator (CFLAR). 57 Additionally, we identified genetic variants in the KSHV entry receptor Eph receptor A2 (EPHA2) to be significantly associated with KSHV infection and KS development.…”

Section: Candidate Susceptibility Genes-current Knowledgementioning

confidence: 99%

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Evidence for altered host genetic factors in KSHV infection and KSHV‐related disease development

Blumenthal

Castro

Whitby

et al. 2020

Reviews in Medical Virology

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Summary Kaposi's sarcoma‐associated herpesvirus (KSHV) is the etiological agent of Kaposi's sarcoma (KS), the most common AIDS‐related malignancy. It also causes other rare, but certainly underreported, KSHV‐associated pathologies, namely primary effusion lymphoma, multicentric Castleman disease and KSHV inflammatory cytokine syndrome. Epidemiology and pathogenicity studies point to the potential for host genetic predisposition to KSHV infection and/or the subsequent development of KSHV‐associated pathologies partly explaining the peculiar geographic and population‐specific incidence of KSHV and associated pathologies and discrepancies in KSHV exposure and infection and KSHV infection and disease development. This review consolidates the current knowledge of host genetic factors involved in the KSHV‐driven pathogenesis. Studies reviewed here indicate a plausible connection between KSHV susceptibility and host genetic factors that affect either viral access to host cells via entry mechanisms or host innate immunity to viral infection. Subsequent to infection, KSHV‐associated pathogenesis, reviewed here primarily in the context of KS, is likely influenced by an orchestrated concert of innate immune system interactions, downstream inflammatory pathways and oncogenic mechanisms. The association studies reviewed here point to interesting candidate genes that may prove important in achieving a more nuanced understanding of the pathogenesis and therapeutic targeting of KSHV and associated diseases. Recent studies on host genetic factors suggest numerous candidate genes strongly associated with KSHV infection or subsequent disease development, particularly innate immune system mediators. Taken together, these contribute toward our understanding of the geographic prevalence and population susceptibility to KSHV and KSHV‐associated diseases.

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“…Control of HHV-8 infection and early stages of KS development are mediated by innate and adaptive immunity responses [15][16][17][18]. In this context, mannose-binding MBL protein expression is genetically determined and variations in plasma concentrations can also be attributed to MBL2 gene polymorphisms, which may cause defects in the polymerization of the molecule leading to functional deficiency and/or serum levels [26,27,[29][30][31][32][33].…”

Section: Introductionmentioning

confidence: 99%