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Viruses
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The Role of NK Cells in Antiviral Innate Immunity
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The Role of NK Cells in Antiviral Innate Immunity

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Animal Viruses".

Deadline for manuscript submissions: closed (31 March 2019) | Viewed by 48937

Special Issue Editors

Dr. Jeanette Boudreau

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Guest Editor
Departments of Microbiology & Immunology and Pathology, Dalhousie University, Halifax, Canada
Interests: We investigate how human natural killer cell immunogenetics program immune responsiveness to cancer and infectious diseases. We use bioinformatics, humanized in vivo models, cell-signal analysis, and highly-parametric flow cytometry to understand how genetic variation creates diversity in human immune potentials. Our interdisciplinary and collaborative work aims to translate research findings into precision therapies.
Dr. Craig McCormick

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Guest Editor
Department of Microbiology and Immunology, Dalhousie University, Sir Charles Tupper Medical Building, Room 7-P 5850 College Street, Halifax, NS B3H 4R2, Canada
Interests: influenza A virus; Kaposi’s sarcoma-associated herpesvirus; viral oncogenes; mRNA turnover and translation; stress granules; p-bodies; autophagy; unfolded protein response; inflammation; host shutoff
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The early and ongoing control of viral infections requires robust host innate immune defences. Innate-like lymphocytes including natural killer (NK) cells are critical and early responders to virus infections and play lead roles in controlling chronic infections by herpes viruses, hepatitis viruses and HIV. Increasingly, subpopulations of NK cells and NK cell immunogenetics are understood to predict the outcomes of virus–host interactions and viral mechanisms to manipulate host innate defences are being uncovered. An increasing body of evidence is demonstrating that viruses have driven the evolution of NK cell function; reciprocally, innate immune defences pressure virus evolution for the increased virulence, latency or polarization of innate immune responses. The goal of this Special Issue of Viruses is to explore interactions between NK cells and viruses.

Primary research and review articles pertaining to virus interactions with NK and NK-related immune populations are invited. Topics of interest include, but are not limited to, the following:

  1. Co-evolution of virus and host defence factors,
  2. Viral mechanisms of immune evasion,
  3. Antiviral mechanisms of NK cells and ILC,
  4. Consequences of virus–host interactions, including immune senescence or viral latency,
  5. Viral pathogenesis by immune evasion or immunopathology,
  6. Interactions between viruses and NK-related immune populations including innate lymphoid cells (ILC), NKT and MAIT cells,
  7. Innate immune-based vaccination and anti-viral immunotherapy.

Dr. Jeanette Boudreau
Dr. Craig McCormick
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Viruses is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • natural killer cells
  • virus
  • NK cells
  • innate immunity
  • anti-viral response
  • co-evolution
  • host-defence
  • innate lymphoid cells
  • invariant T cells (NKT, MAIT, γδT cells)

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Published Papers (8 papers)

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Research

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17 pages, 1705 KiB  
Article
Quantifying Anti-HIV Envelope-Specific Antibodies in Plasma from HIV Infected Individuals
by Sanket Kant, Ningyu Zhang, Jean-Pierre Routy, Cécile Tremblay, Réjean Thomas, Jason Szabo, Pierre Côté, Benoit Trottier, Roger LeBlanc, Danielle Rouleau, Marianne Harris, Franck P. Dupuy and Nicole F. Bernard
Viruses 2019, 11(6), 487; https://doi.org/10.3390/v11060487 - 28 May 2019
Cited by 11 | Viewed by 4149
Abstract
Quantifying HIV Envelope (Env)-specific antibodies in HIV+ plasma is useful for interpreting antibody dependent cellular cytotoxicity assay results. HIV Env, the only viral protein expressed on the surface of infected cells, has a native trimeric closed conformation on cells infected with wild-type [...] Read more.
Quantifying HIV Envelope (Env)-specific antibodies in HIV+ plasma is useful for interpreting antibody dependent cellular cytotoxicity assay results. HIV Env, the only viral protein expressed on the surface of infected cells, has a native trimeric closed conformation on cells infected with wild-type HIV. However, CD4+ uninfected bystander cells in HIV+ cell cultures bind gp120 shed from HIV+ cells exposing CD4-induced epitopes normally hidden in native Env. We used flow-cytometry based assays to quantify antibodies in HIV+ plasma specific for native trimeric Env or gp120/CD4 conjugates using CEM.NKr.CCR5 (CEM) cells infected with HIV (iCEM) or coated with recombinant gp120 (cCEM), as a surrogate for gp120+ HIV- bystander cells. Results from both assays were compared to those of a plate-based ELISA to monomeric gp120. The levels of Env-specific antibodies to cCEM and iCEM, measured by flow cytometry, and to gp120 by ELISA were positively correlated. More antibodies in HIV+ plasma recognized the gp120 conformation exposed on cCEM than on iCEM. Comparisons of plasma from untreated progressors, treated progressors, and elite controllers revealed that antibodies to Env epitopes were the lowest in treated progressors. Plasma from elite controllers and untreated progressors had similarly high levels of Env-specific antibodies, despite elite controllers having undetectable HIV viral loads, while untreated progressors maintained high viral loads. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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14 pages, 4914 KiB  
Article
Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2Cnull Human Immunodeficiency Virus-Infected Individuals
by Emilie M. Comeau, Kayla A. Holder, Neva J. Fudge and Michael D. Grant
Viruses 2019, 11(3), 239; https://doi.org/10.3390/v11030239 - 9 Mar 2019
Cited by 10 | Viewed by 4503
Abstract
Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate FcεRIγ and promyelocytic leukemia zinc finger protein (PLZF). Lacking [...] Read more.
Expansion of natural killer (NK) cells expressing NKG2C occurs following human cytomegalovirus (HCMV) infection and is amplified by human immunodeficiency virus (HIV) co-infection. These NKG2C-expressing NK cells demonstrate enhanced CD16-dependent cytokine production and downregulate FcεRIγ and promyelocytic leukemia zinc finger protein (PLZF). Lacking NKG2C diminishes resistance to HIV infection, but whether this affects NK cell acquisition of superior antibody-dependent function is unclear. Therefore, our objective was to investigate whether HCMV-driven NK cell differentiation is impaired in NKG2Cnull HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, FcεRIγ, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV–infected NKG2Cnull and NKG2C-expressing groups. Cytokine production was compared following stimulation through natural cytotoxicity receptors or through CD16. Cytotoxicity was measured by anti-CD16-redirected lysis and by classical antibody-dependent cell-mediated cytotoxicity (ADCC) against anti-class I human leukocyte antigen (HLA) antibody-coated cells. Our data indicate highly similar HCMV-driven NK cell differentiation in HIV infection with or without NKG2C. While the fraction of mature (CD57pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2Cnull HIV-infected individuals, there were no significant differences in NKG2A, FcεRIγ, or PLZF expression. The general phenotypic and functional equivalency observed suggests NKG2C-independent routes of HCMV-driven NK cell differentiation, which may involve increased CD2 expression. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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Review

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17 pages, 992 KiB  
Review
The Evolutionary Arms Race between Virus and NK Cells: Diversity Enables Population-Level Virus Control
by Sarah K. A. Savoy and Jeanette E. Boudreau
Viruses 2019, 11(10), 959; https://doi.org/10.3390/v11100959 - 17 Oct 2019
Cited by 24 | Viewed by 7053
Abstract
Viruses and natural killer (NK) cells have a long co-evolutionary history, evidenced by patterns of specific NK gene frequencies in those susceptible or resistant to infections. The killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) ligands together form the most polymorphic [...] Read more.
Viruses and natural killer (NK) cells have a long co-evolutionary history, evidenced by patterns of specific NK gene frequencies in those susceptible or resistant to infections. The killer immunoglobulin-like receptors (KIR) and their human leukocyte antigen (HLA) ligands together form the most polymorphic receptor-ligand partnership in the human genome and govern the process of NK cell education. The KIR and HLA genes segregate independently, thus creating an array of reactive potentials within and between the NK cell repertoires of individuals. In this review, we discuss the interplay between NK cell education and adaptation with virus infection, with a special focus on three viruses for which the NK cell response is often studied: human immunodeficiency virus (HIV), hepatitis C virus (HCV) and human cytomegalovirus (HCMV). Through this lens, we highlight the complex co-evolution of viruses and NK cells, and their impact on viral control. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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18 pages, 1636 KiB  
Review
Mast Cells and Natural Killer Cells—A Potentially Critical Interaction
by Liliana Portales-Cervantes, Bassel Dawod and Jean S. Marshall
Viruses 2019, 11(6), 514; https://doi.org/10.3390/v11060514 - 4 Jun 2019
Cited by 17 | Viewed by 7117
Abstract
Natural killer (NK) cells play critical roles in host defense against infectious agents or neoplastic cells. NK cells provide a rapid innate immune response including the killing of target cells without the need for priming. However, activated NK cells can show improved effector [...] Read more.
Natural killer (NK) cells play critical roles in host defense against infectious agents or neoplastic cells. NK cells provide a rapid innate immune response including the killing of target cells without the need for priming. However, activated NK cells can show improved effector functions. Mast cells are also critical for early host defense against a variety of pathogens and are predominately located at mucosal surfaces and close to blood vessels. Our group has recently shown that virus-infected mast cells selectively recruit NK cells and positively modulate their functions through mechanisms dependent on soluble mediators, such as interferons. Here, we review the possible consequences of this interaction in both host defense and pathologies involving NK cell and mast cell activation. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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11 pages, 694 KiB  
Review
Treatment of Metastatic Disease through Natural Killer Cell Modulation by Infected Cell Vaccines
by Seyedeh Raheleh Niavarani, Christine Lawson and Lee-Hwa Tai
Viruses 2019, 11(5), 434; https://doi.org/10.3390/v11050434 - 11 May 2019
Cited by 4 | Viewed by 4357
Abstract
Oncolytic viruses (OVs) are a form of immunotherapy that release tumor antigens in the context of highly immunogenic viral signals following tumor-targeted infection and destruction. Emerging preclinical and clinical evidence suggests that this in situ vaccine effect is critical for successful viro-immunotherapy. In [...] Read more.
Oncolytic viruses (OVs) are a form of immunotherapy that release tumor antigens in the context of highly immunogenic viral signals following tumor-targeted infection and destruction. Emerging preclinical and clinical evidence suggests that this in situ vaccine effect is critical for successful viro-immunotherapy. In this review, we discuss the application of OV as an infected cell vaccine (ICV) as one method of enhancing the potency and breadth of anti-tumoral immunity. We focus on understanding and manipulating the critical role of natural killer (NK) cells and their interactions with other immune cells to promote a clinical outcome. With a synergistic tumor killing and immune activating mechanism, ICVs represent a valuable new addition to the cancer fighting toolbox with the potential to treat malignant disease. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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13 pages, 2005 KiB  
Review
Tissue-Resident Innate and Innate-Like Lymphocyte Responses to Viral Infection
by Andrew D. Hildreth and Timothy E. O’Sullivan
Viruses 2019, 11(3), 272; https://doi.org/10.3390/v11030272 - 19 Mar 2019
Cited by 16 | Viewed by 5574
Abstract
Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Recent discoveries have demonstrated that tissue-resident lymphocyte subsets, comprised of innate lymphoid cells (ILCs) and unconventional T cells, have vital roles in the initiation of primary antiviral responses. Via direct [...] Read more.
Infection is restrained by the concerted activation of tissue-resident and circulating immune cells. Recent discoveries have demonstrated that tissue-resident lymphocyte subsets, comprised of innate lymphoid cells (ILCs) and unconventional T cells, have vital roles in the initiation of primary antiviral responses. Via direct and indirect mechanisms, ILCs and unconventional T cell subsets play a critical role in the ability of the immune system to mount an effective antiviral response through potent early cytokine production. In this review, we will summarize the current knowledge of tissue-resident lymphocytes during initial viral infection and evaluate their redundant or nonredundant contributions to host protection or virus-induced pathology. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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13 pages, 2831 KiB  
Review
Viral Infection of Human Natural Killer Cells
by Elisabeth A. van Erp, Mirjam R. van Kampen, Puck B. van Kasteren and Jelle de Wit
Viruses 2019, 11(3), 243; https://doi.org/10.3390/v11030243 - 12 Mar 2019
Cited by 74 | Viewed by 9122
Abstract
Natural killer (NK) cells are essential in the early immune response against viral infections, in particular through clearance of virus-infected cells. In return, viruses have evolved multiple mechanisms to evade NK cell-mediated viral clearance. Several unrelated viruses, including influenza virus, respiratory syncytial virus, [...] Read more.
Natural killer (NK) cells are essential in the early immune response against viral infections, in particular through clearance of virus-infected cells. In return, viruses have evolved multiple mechanisms to evade NK cell-mediated viral clearance. Several unrelated viruses, including influenza virus, respiratory syncytial virus, and human immunodeficiency virus, can directly interfere with NK cell functioning through infection of these cells. Viral infection can lead to immune suppression, either by downregulation of the cytotoxic function or by triggering apoptosis, leading to depletion of NK cells. In contrast, some viruses induce proliferation or changes in the morphology of NK cells. In this review article, we provide a comprehensive overview of the viruses that have been reported to infect NK cells, we discuss their mechanisms of entry, and describe the interference with NK cell effector function and phenotype. Finally, we discuss the contribution of virus-infected NK cells to viral load. The development of specific therapeutics, such as viral entry inhibitors, could benefit from an enhanced understanding of viral infection of NK cells, opening up possibilities for the prevention of NK cell infection. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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15 pages, 1035 KiB  
Review
Control of Acute Arboviral Infection by Natural Killer Cells
by Christopher Maucourant, Caroline Petitdemange, Hans Yssel and Vincent Vieillard
Viruses 2019, 11(2), 131; https://doi.org/10.3390/v11020131 - 31 Jan 2019
Cited by 23 | Viewed by 5369
Abstract
The recent explosive pandemic of chikungunya virus (CHIKV) followed by Zika (ZIKV) virus infections occurring throughout many countries represents the most unexpected arrival of arthropod-borne viral diseases in the past 20 years. Transmitted through the bite of Aedes mosquitoes, the clinical picture associated [...] Read more.
The recent explosive pandemic of chikungunya virus (CHIKV) followed by Zika (ZIKV) virus infections occurring throughout many countries represents the most unexpected arrival of arthropod-borne viral diseases in the past 20 years. Transmitted through the bite of Aedes mosquitoes, the clinical picture associated with these acute arbovirus infections, including Dengue (DENV), CHIKV and ZIKV, ranges from classical febrile illness to life-threatening disease. Whereas ZIKV and CHIKV-mediated infections have previously been recognized as relatively benign diseases, in contrast to Dengue fever, recent epidemic events have brought waves of increased morbidity and mortality leading to a serious public health problem. Although the host immune response plays a crucial role in controlling infections, it may also promote viral spread and immunopathology. Here, we review recent developments in our understanding of the immune response, with an emphasis on the early antiviral immune response mediated by natural killer cells and emphasize their Janus-faced effects in the control of arbovirus infection and pathogenesis. Improving our understanding knowledge on of the mechanisms that control viral infection is crucial in the current race against the globalization of arbovirus epidemics. Full article
(This article belongs to the Special Issue The Role of NK Cells in Antiviral Innate Immunity)
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