scholarly journals Association of Dementia Human Leukocyte Antigen (HLA) Profile with Human Herpes Viruses 3 and 7: An in-silico Investigation

2021 ◽  
Vol 5 (3) ◽  
pp. 7-14
Author(s):  
Lisa M. James ◽  
Spyros A. Charonis ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
In Silico ◽  
Human Leukocyte ◽  
Binding Affinities ◽  
Herpes Viruses ◽  
Human Herpes ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Dementia Risk ◽  
Human Herpes Viruses

Human leukocyte antigen (HLA), the most highly polymorphic region of the human genome, is increasingly recognized as an important genetic contributor to dementia risk and resilience. HLA is involved in protection against foreign antigens including human herpes viruses (HHV), which have been widely implicated in dementia. Here we used an in silico approach1 to determine binding affinities of glycoproteins from 9 human herpes virus (HHV) strains to 113 HLA alleles, and to examine the association of a previously identified HLA-dementia risk profile2 to those affinities. We found a highly significant correlation between high binding affinities of HLA alleles to HHV 3 and 7 and the dementia risk scores of those alleles, such that the higher the estimated binding affinity, the lower the dementia risk score. These findings suggest that protection conferred by HLA alleles may be related to their ability to bind and eliminate HHV3 and HHV7 and point to the possibility that protection against these viruses may reduce dementia incidence.

scholarly journals In silico investigation of binding affinities between human leukocyte antigen class I molecules and SARS-CoV-2 virus spike and ORF1ab proteins

2021 ◽  
Author(s):  
Spyros A. Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos P. Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
In Silico ◽  
Human Leukocyte ◽  
Hla Class I ◽  
Hla Class Ii ◽  
Class I ◽  
Binding Affinities ◽  
S Protein ◽  
Leukocyte Antigen ◽  
Hla Class I Molecules

Aim: The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019, a global pandemic. There is hence an urgent need for effective approaches to understand the mechanism of viral interaction with immune cells that lead to viral elimination and subsequent long-term immunity. The first, immediate response to the viral infection involves mobilization of native immunity and human leukocyte antigen (HLA) class I mechanisms to kill infected cells and eliminate the virus. The second line of defense involves the activation of HLA class II system for the production of antibodies against the virus which will add to the elimination of the virus and prevent future infections. In a previous study, investigated the relations between SARS-CoV-2 spike glycoprotein (S protein) and HLA class II alleles were investigaed; here report on the relations of the S protein and the open reading frame 1ab (ORF1ab) of SARS-CoV-2 to HLA class I alleles. Methods: An in silico sliding window approach was used to determine exhaustively the binding affinities of linear epitopes of 10 amino acid length (10-mers) to each of 61 common (global frequency ≥ 0.01) HLA class I molecules (17, 24 and 20 from gene loci A, B and C, respectively). A total of 8,354 epitopes were analyzed; 1,263 from the S protein and 7,091 from ORF1ab. Results: HLA-A genes were the most effective at binding SARS-CoV-2 epitopes for both spike and ORF1ab proteins. Good binding affinities were found for all three genes and were distributed throughout the length of the S protein and ORF1ab polyprotein sequence. Conclusions: Common HLA class I molecules, as a population, are very well suited to binding with high affinity to SARS-CoV-2 spike and ORF1ab proteins and hence should be effective in aiding the early elimination of the virus.

scholarly journals SARS-CoV-2 Virus and Human Leukocyte Antigen (HLA) Class II: Investigation in silico of Binding Affinities for COVID-19 Protection and Vaccine Development

2020 ◽  
Vol 4 (4) ◽  
pp. 12-23 ◽  
Author(s):  
Spyros Charonis ◽  
Effie-Photini Tsilibary ◽  
Apostolos Georgopoulos
Keyword(s):  
Human Leukocyte Antigen ◽  
Binding Affinity ◽  
In Silico ◽  
Vaccine Development ◽  
Human Leukocyte ◽  
Class Ii ◽  
Hla Class Ii ◽  
Effective Vaccine ◽  
Binding Affinities ◽  
Leukocyte Antigen

SARS-CoV-2 causes COVID-19, urgently requiring the development of effective vaccine(s). Much of current efforts focus on the SARS-CoV-2 spike-glycoprotein by identifying highly antigenic epitopes as good vaccine candidates. However, high antigenicity is not sufficient, since the activation of relevant T cells depends on the presence of the complex of the antigen with a suitably matching Human Leukocyte Antigen (HLA) Class II molecule, not the antigen alone: in the absence of such a match, even a highly antigenic epitope in vitro will not elicit antibody formation in vivo. Here we assessed systematically in silico the binding affinity of epitopes of the spike-glycoprotein to 66 common HLA-Class-II alleles (frequency ≥ 0.01). We used a sliding epitope window of 22-amino-acid-width to scan the entire protein and determined the binding affinity of each subsequence to each HLA allele. DPB1 had highest binding affinities, followed by DRB1 and DQB1. Higher binding affinities were concentrated in the initial part of the glycoprotein (S1-S460), with a peak at S223-S238. This region would be well suited for effective vaccine development by ensuring high probability for successful matching of the vaccine antigen from that region to a HLA Class II molecule for CD4+ T cell activation by the antigen-HLA molecule complex.

scholarly journals Non-inherited maternal human leukocyte antigen alleles in susceptibility to familial rheumatoid arthritis

2008 ◽  
Vol 68 (1) ◽  
pp. 107-109 ◽  
Author(s):  
K A Guthrie ◽  
N R Tishkevich ◽  
J L Nelson
Keyword(s):  
Rheumatoid Arthritis ◽  
Human Leukocyte Antigen ◽  
Age Of Onset ◽  
Human Leukocyte ◽  
Paternal Allele ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
The North ◽  
Significant Difference ◽  
Hla Genotype

Objectives:Some patients with rheumatoid arthritis (RA) lack RA-associated human leukocyte antigen (HLA) alleles. Prior studies investigated non-inherited maternal HLA alleles (NIMA) in RA risk with conflicting results.Methods:We examined NIMA in a large cohort of families from the North American Rheumatoid Arthritis Consortium (NARAC).Results:Among 620 patients with 1 or both parents having a HLA genotype, patients with RA informative for analysis included 176 without HLA-DRB1*04 and 86 without the HLA shared epitope (SE). The frequency of NIMA encoding HLA-DR4 or the SE was compared to the non-inherited paternal allele (NIPA). DR4-encoding NIMA vs NIPA revealed no significant difference (27% vs 20%). However, parity is known to modulate RA risk and analyses stratified by sex and age of onset showed significant variation among women. Interestingly, among women with onset <45 years DR4-encoding NIMA was increased compared to NIPA; among women ⩾45 years at onset the reverse was observed (31% vs 16% compared to 10% vs 60%, p = 0.008). DR4 encoding NIMA vs NIPA did not differ in men. The SE did not differ in men or women.Conclusions:Risk of RA was associated with HLA-DR4 encoding NIMA in younger-onset women but not in older-onset women or men. These observations could help explain conflicting prior results of NIMA in RA.

scholarly journals PIRCHE-II: an algorithm to predict indirectly recognizable HLA epitopes in solid organ transplantation

2019 ◽  
Vol 72 (1-2) ◽  
pp. 119-129 ◽  
Author(s):  
Kirsten Geneugelijk ◽  
Eric Spierings
Keyword(s):  
Human Leukocyte Antigen ◽  
Organ Transplantation ◽  
Graft Survival ◽  
Solid Organ Transplantation ◽  
Human Leukocyte ◽  
Solid Organ ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
Hla System ◽  
Hla Mismatches

AbstractHuman leukocyte antigen (HLA) mismatches between donors and recipients may lead to alloreactivity after solid organ transplantation. Over the last few decades, our knowledge of the complexity of the HLA system has dramatically increased, as numerous new HLA alleles have been identified. As a result, the likelihood of alloreactive responses towards HLA mismatches after solid organ transplantation cannot easily be assessed. Algorithms are promising solutions to estimate the risk for alloreactivity after solid organ transplantation. In this review, we show that the recently developed PIRCHE-II (Predicted Indirectly ReCognizable HLA Epitopes) algorithm can be used to minimize alloreactivity towards HLA mismatches. Together with the use of other algorithms and simulation approaches, the PIRCHE-II algorithm aims for a better estimated alloreactive risk for individual patients and eventually an improved graft survival after solid organ transplantation.

scholarly journals Hepatitis B infection outcome is associated with novel human leukocyte antigen variants in Ghanaian cohort

2020 ◽  
Vol 245 (9) ◽  
pp. 815-822
Author(s):  
Kwesi Z Tandoh ◽  
Kwadwo A Kusi ◽  
Timothy N Archampong ◽  
Isaac Boamah ◽  
Osbourne Quaye
Keyword(s):  
Hepatitis B Virus ◽  
Hepatitis B ◽  
Human Leukocyte Antigen ◽  
Human Leukocyte ◽  
P Value ◽  
Hepatitis B Infection ◽  
Virus Persistence ◽  
Hla Alleles ◽  
Leukocyte Antigen ◽  
B Virus

Chronic hepatitis B infection is an important medical problem in sub-Saharan Africa. With increasing concerns of dwindling access to needed care, increasing cost of treatment, and rising prevalence of dire outcomes like liver cirrhosis and hepatocellular cancer, the need to determine the genetic associations underpinning hepatitis B virus persistence or clearance in a population comes to the fore. Genetic association studies have suggested a variation in human leukocyte antigen alleles associated with hepatitis B virus outcome along geo-ethnic lines. We investigated the association of human leukocyte antigen alleles to hepatitis B virus outcome against this backdrop. We used targeted next generation sequencing to type the human leukocyte antigen class I and II alleles of 173 study participants. These comprised of 92 cases with chronic hepatitis B infection and 81 healthy controls with serological evidence of naturally cleared hepatitis B virus infection. We have identified human leukocyte antigen alleles associated with hepatitis B virus clearance and persistence for the first time in a Ghanaian population. The class 1 allele C*16:01 (odds ratio (OR) = 3.4, confidence interval (CI) = 1.6–7.0, P-value = 0.01) was associated with hepatitis B virus persistence. Four class I alleles and one class II allele: A*34:02 (OR = 0.1, CI = 0.04–0.2, P-value = 3.4e-05), A*74:01 (OR = 0.3, CI = 0.2–0.7, P-value = 0.0135), B*13:02 (OR = 0.04, CI = 0.01–0.2, P-value = 0.000172), C*08:04 (OR = 0.06, CI = 0.01–0.2, P-value = 7.83e-05), and DRB1*08:04 (OR = 0.2, CI = 0.03–0.27, P-value = 0.000252) were associated with hepatitis B virus clearance. Our data show that previously reported human leukocyte antigen alleles associations to hepatitis B virus outcome are not found in this Ghanaian study. This study has therefore identified human leukocyte antigen types that are associated with either hepatitis B virus persistence or clearance and highlights the importance of geo-ethnic pivoted studies in determining the genetic associations to acute hepatitis B virus infection outcome. Impact statement Genetic association studies can determine the effect size of gene loci on disease outcomes. In the arena of HBV infections, HLA alleles that associate with HBV outcomes can be used in clinical management decisions. This potential translational utility can shape the future management of HBV infections by identifying at-risk individuals and tailoring medical interventions accordingly. This precision medicine motif is currently only a nascent idea. However, it has stakes that may well override the current “wait and see” approach of clinical management of HBV infections. Here, we have identified HLA alleles associated with HBV outcome in a Ghanaian cohort. Our findings support the motif that HLA alleles associate with HBV outcome along geo-ethnic lines. This buttresses the need for further population pivoted studies. In the long term, our findings add to efforts towards the development of an HLA molecular-based algorithm for predicting HBV infection outcomes.

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