Herpesvirus Evasion of Natural Killer Cells

Pelsmaeker, Steffi De; Romero, Nicolás; Vitale, Massimo; Favoreel, Herman

doi:10.1128/jvi.02105-17

Cited by 66 publications

(69 citation statements)

References 139 publications

(169 reference statements)

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“…Two NK cell subsets might play a critical role in the immune response against Dengue virus infection [286]. NK cells are important in herpes virus infections as patients with de iciencies of NK cells experience systemic and lifethreatening infections that are caused by herpes viruses [287]. VZV productively infects human NK cells and actively manipulates their phenotype thus NK cells play a potential role in the pathogenesis of VZV infections [288].…”

Section: Nk Cells In Solid Tumorsmentioning

confidence: 99%

“…In immunocompromised hosts including recipients of HSCT and cancer patients, recovery of the immune system has a major impact on the outcome of infectious complications that represent a signi icant cause of morbidity and mortality in this group of patients [163,287]. Strategies that can be employed to strengthen the host immune response to counteract infections include the use of: growth factors; speci ic cytokines and adoptive cellular therapies such as granulocyte transfusions, pathogen-speci ic T-cells and adoptive transfer of NK cells [163].…”

Section: Nk Cells In Solid Tumorsmentioning

confidence: 99%

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Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

Ka¹,

Al-Jasser²,

Wk³

2019

J Stem Cell Ther Transplant

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Section: Nk Cells In Solid Tumorsmentioning

confidence: 99%

Section: Nk Cells In Solid Tumorsmentioning

confidence: 99%

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

Ka¹,

Al-Jasser²,

Wk³

2019

J Stem Cell Ther Transplant

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“…The human herpesviruses are highly host adapted [2] and possess the capacity for latency [3], allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response [4] poses particular challenges for vaccine development [5] but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine [6,7].…”

Section: Introductionmentioning

confidence: 99%

Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

Maple

2020

Vaccines

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Herpesviruses have been isolated from a wide range of hosts including humans—for which, nine species have been designated. The human herpesviruses are highly host adapted and possess the capacity for latency, allowing them to survive in the host for life, effectively hidden from the immune system. This ability of human herpesviruses to modulate the host immune response poses particular challenges for vaccine development but at the same time proves attractive for the application of human herpesvirus vaccines to certain spheres of medicine. In this review, congenital cytomegalovirus (CMV) infection and hearing loss will be described followed by a comment on the status of current vaccine development. Secondly, the association of Epstein–Barr virus (EBV) infection with multiple sclerosis (MS) and how EBV vaccination may be of benefit will then be discussed. Prevention of congenital CMV by vaccination is an attractive proposition and several vaccines have been evaluated for potential use. Particularly challenging for the development of CMV vaccines are the needs to prevent primary infection, reinfection, and reactivation at the same time as overcoming the capacity of the virus to generate highly sophisticated immunomodulatory mechanisms. Cost and the practicalities of administering potential vaccines are also significant issues, particularly for low- and middle-income countries, where the burden of disease is greatest. An effective EBV vaccine that could prevent the 200,000 new EBV-associated malignancies which occur globally each year is not currently available. There is increasing interest in developing EBV vaccines to prevent MS and, in view of the association of infectious mononucleosis with MS, reducing childhood infectious mononucleosis is a potential intervention. Currently, there is no licensed EBV vaccine and, in order to progress the development of EBV vaccines for preventing MS, a greater understanding of the association of EBV with MS is required.

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“…HCMV targets the NKG2D stress-induced ligands by multiple and diverse immune evasion mechanisms, including by manipulation of the ubiquitin proteasome system (23)(24)(25). The viral microRNA miR-UL112 inhibits MICB translation (26).…”

Section: Introductionmentioning

confidence: 99%

The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing

Seidel¹,

Dassa²,

Oiknine‐Djian

et al. 2020

Preprint

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Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells without prior sensitization. NK cell activity is regulated by signals received from activating and inhibitory receptors. One pivotal activating NK receptor is NKG2D, which binds a family of eight ligands, including the major histocompatibility complex (MHC) class I-related chain A (MICA). Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunosuppressed patients and congenitally infected infants. HCMV encodes multiple antagonists of NK cell activation, including many mechanisms targeting MICA. However, only one of these mechanisms counters the most prevalent MICA allele, MICA*008. Here, we discover that a hitherto uncharacterized HCMV protein, UL147A, specifically targets MICA*008 to proteasomal degradation, thus hindering the elimination of HCMV-infected cells by NK cells. Mechanistic analyses disclose that the non-canonical GPI anchoring pathway of immature MICA*008 constitutes the determinant of UL147A specificity for this MICA allele. These findings advance our understanding of the complex and rapidly evolving HCMV immune evasion mechanisms, which may facilitate the development of antiviral drugs and vaccines.

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Herpesvirus Evasion of Natural Killer Cells

Cited by 66 publications

References 139 publications

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

Natural killer cells in patients with hematologic malignancies, solid tumors and in recipients of hematopoietic stem cell transplantation

Cytomegalovirus and Epstein–Barr Virus Associations with Neurological Diseases and the Need for Vaccine Development

The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing

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