COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

Pontarotti, Pierre; Paganini, Julien

doi:10.3390/ijms23052665

Cited by 5 publications

(9 citation statements)

References 71 publications

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“…HLA genes, which are important targets for natural selection, were the most polymorphic genes in the human genome ( 46 ). HLA molecules serve as an important factor for regulating the outcome of various infections in the host organism and stand out as a leading candidate for disease susceptibility, and it has been recognized that HLA molecules play a central role in antigen presentation and additionally provide modulation of NK cell activity ( 8 , 47 ).…”

Section: Discussionmentioning

confidence: 99%

Immune modulation as a consequence of SARS-CoV-2 infection

et al. 2022

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Erroneous immune responses in COVID-19 could have detrimental effects, which makes investigation of immune network underlying COVID-19 pathogenesis a requisite. This study aimed to investigate COVID-19 related alterations within the frame of innate and adaptive immunity. Thirty-four patients clinically diagnosed with mild, moderate and severe COVID-19 disease were enrolled in this study. Decreased ILC1 and increased ILC2 subsets were detected in mild and moderate patients compared to healthy controls. NK cell subsets and cytotoxic capacity of NK cells were decreased in severe patients. Moreover, CD3+ T cells were reduced in severe patients and a negative correlation was found between CD3+ T cells and D-dimer levels. Likewise, moderate and severe patients showed diminished CD3+CD8+ T cells. Unlike T and NK cells, plasmablast and plasma cells were elevated in patients and IgG and IgA levels were particularly increased in severe patients. Severe patients also showed elevated serum levels of pro-inflammatory cytokines such as TNF-α, IL-6 and IL-8, reduced intracellular IFN-γ and increased intracellular IL-10 levels. Our findings emphasize that SARS-CoV-2 infection significantly alters immune responses and innate and acquired immunity are differentially modulated in line with the clinical severity of the disease. Elevation of IL-10 levels in NK cells and reduction of CD3+ and CD8+ T cells in severe patients might be considered as a protective response against the harmful effect of cytokine storm seen in COVID-19.

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Section: Discussionmentioning

confidence: 99%

Immune modulation as a consequence of SARS-CoV-2 infection

et al. 2022

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“…Unlike other mechanisms, ongoing pathogen evolution is required to escape effective presentation of their antigens by the host's MHC to T‐cells. Several potential mechanisms of such escape have been considered 8,28 . First, evasion might occur via escape from effective MHC binding, as documented in HIV and a few other pathogens 29,30 .…”

Section: Immune Memory and Selection On Mhcmentioning

confidence: 99%

“…Several potential mechanisms of such escape have been considered. 8,28 First, evasion might occur via escape from effective MHC binding, as documented in HIV and a few other pathogens. 29,30 Another route of escape would favour mutations in TCR epitopes, which exploit holes in the host's TCR repertoire that might result from MHC-dependent thymic selection against self-reacting lymphocytes.…”

Section: Immune Memory and Selection On Mhcmentioning

confidence: 99%

Integration of the immune memory into the pathogen‐driven MHC polymorphism hypothesis

Radwan,

Kohi,

Ejsmond

et al. 2023

HLA

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Major histocompatibility complex (MHC) genes (referred to as human leukocyte antigen or HLA in humans) are a key component of vertebrate immune systems, coding for proteins which present antigens to T‐cells. These genes are outstanding in their degree of polymorphism, with important consequences for human and animal health. The polymorphism is thought to arise from selection pressures imposed by pathogens on MHC allomorphs, which differ in their antigen‐binding capacity. However, the existing theory has not considered MHC selection in relation to the formation of immune memory. In this paper, we argue that this omission limits our understanding of the evolution of MHC polymorphism and its role in disease. We review recent evidence that has emerged from the massive research effort related to the SARS‐CoV‐2 pandemics, and which provides new evidence for the role of MHC in shaping immune memory. We then discuss why the inclusion of immune memory within the existing theory may have non‐trivial consequence for our understanding of the evolution of MHC polymorphism. Finally, we will argue that neglecting immune memory hinders our interpretation of empirical findings, and postulate that future studies focusing on pathogen‐driven MHC selection would benefit from stratifying the available data according to the history of infection (and vaccination, if relevant).

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“…Deletions in S protein leads to loss of seven CD8 + and twelve except the one's derived from S protein which also indicates an intact T cell immunity against the variant (Ahmed et al, 2021;Flemming., 2022). Moreover, mutations in regions not recognized by MHC allotypes do not affect memory (Pontarotti et al, 2022). Omicron is found to be resistant to mAb like casirivimab and imdevimab (Wilhelm et al, 2021).…”

Section: Delta Variant (B16172)mentioning

confidence: 99%

Immunity Escape of SARS-CoV-2 Variants: Omicron Leads the Way

Dhingra¹,

Sharma²,

Balda³

et al. 2022

Preprint

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With the emergence of COVID-19 pandemic in 2019, the world saw a humungous loss of human life and economic resources globally but also the rapid appearance of SARS-CoV-2 variants which have exhibited a higher transmissibility and/or virulence and which also evade immune system to such an extent that it raises a big question mark on the efficacy of current diagnostics, vaccines and convalescent plasma and mAb therapies. This has been attributed to the emergence of huge spectrum of mutations, especially in the virus’s spike (S) protein, occurring in regions harboring high concentration of B cell epitopes thus allowing neutralizing antibody escape. The mutations resulting in ACE 2 receptor recognition failure (T19R), unfavorable electrostatic interactions (E484K), structural change (∆69-70), disruption of hydrogen bonds, salt bridges or hydrophobic interactions (K417N, N501Y, ∆Y145) and change in orientation (N501Y) cause strong immune evasion by these variants. Further, the recent emergence of Omicron with more than 30 mutations in the S protein VOC allows it to escape and fail diagnosis as well as immune system and the protection generated by different vaccination regimes. Yet Omicron may not be the end of the story. This review presents an insight of the immunity escape and its mechanisms followed by different SARS-CoV-2 variant of concerns.

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COVID-19 Pandemic: Escape of Pathogenic Variants and MHC Evolution

Cited by 5 publications

References 71 publications

Immune modulation as a consequence of SARS-CoV-2 infection

Immune modulation as a consequence of SARS-CoV-2 infection

Integration of the immune memory into the pathogen‐driven MHC polymorphism hypothesis

Immunity Escape of SARS-CoV-2 Variants: Omicron Leads the Way

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