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17 pages, 1705 KiB

Open AccessArticle

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 3506

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

Open AccessArticle

Cytomegalovirus-Driven Adaption of Natural Killer Cells in NKG2C^null 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 9 | Viewed by 3839

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 NKG2C^null HIV-infected individuals. Phenotypic (CD2, CD16, CD57, NKG2A, FcεRIγ, and PLZF expression) and functional (cytokine induction and cytotoxicity) properties were compared between HIV–infected NKG2C^null 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 (CD57^pos) NK cells expressing CD2 (p = 0.009) or co-expressing CD2 and CD16 (p = 0.03) was significantly higher in NKG2C^null 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

Jump to: Research

17 pages, 992 KiB

Open AccessReview

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 21 | Viewed by 6154

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

Open AccessReview

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 14 | Viewed by 6109

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

Open AccessReview

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 3832

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

Open AccessReview

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 12 | Viewed by 4899

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

Open AccessReview

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 57 | Viewed by 7504

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

Open AccessReview

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 21 | Viewed by 4698

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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