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Viruses
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Natural Killer Cell in Viral Infection
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Natural Killer Cell in Viral Infection

A special issue of Viruses (ISSN 1999-4915). This special issue belongs to the section "Viral Immunology, Vaccines, and Antivirals".

Deadline for manuscript submissions: closed (31 October 2024) | Viewed by 11004

Special Issue Editor

Prof. Dr. Min Fang

E-Mail Website
Guest Editor
School of Life Sciences, Henan University, Kaifeng 475004, China
Interests: the role and mechanism of NK cells in viral infection; mechanism of NK in controlling early virus replication and transmission; the mechanisms by which NK cells recognize virus infected cells; the role of different subgroups of NK cell during viral infection; the functional change of NK cells with aging; the impact and mechanism of NK cell response on subsequent T and B cell responses

Special Issue Information

Dear Colleagues,

NK cells are a critical cell population in innate immunity, playing roles in antiviral and anti-tumor immunity. Nevertheless, how NK cells function to address these challenges remains poorly understood. Meanwhile, NK cell function declines with aging, which has a critical impact on overall immunity in the elderly. Understanding the molecular and cellular mechanisms involved in NK cell activation, expansion, and memory will reveal possible pathways to enhance NK cell function and enhance immunity against viral infections. 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. Innate recognition of NK cells during viral infection;
  2. Generation and regulation of NK cell memory;
  3. Defects in NK cell function with aging and viral infection.

Prof. Dr. Min Fang
Guest Editor

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

  • NK cells
  • viral infection
  • innate immune responses
  • signaling pathway
  • virus replication and transmission
  • NK cell receptors

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Published Papers (6 papers)

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Editorial

Jump to: Research, Review

3 pages, 163 KiB  
Editorial
Natural Killer Cells in Viral Infection: Special Issue Editorial
by Min Fang
Viruses 2025, 17(3), 391; https://doi.org/10.3390/v17030391 - 10 Mar 2025
Viewed by 504
Abstract
NK cells are a critical cell population in innate immunity, playing an important role in antiviral immunity [...] Full article
(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)

Research

Jump to: Editorial, Review

12 pages, 1079 KiB  
Communication
NTB-A and 2B4 Natural Killer Cell Receptors Modulate the Capacity of a Cocktail of Non-Neutralizing Antibodies and a Small CD4-Mimetic to Eliminate HIV-1-Infected Cells by Antibody-Dependent Cellular Cytotoxicity
by Lorie Marchitto, Alexandra Tauzin, Mehdi Benlarbi, Guillaume Beaudoin-Bussières, Katrina Dionne, Étienne Bélanger, Debashree Chatterjee, Catherine Bourassa, Halima Medjahed, Derek Yang, Ta-Jung Chiu, Hung-Ching Chen, Amos B. Smith III, Jonathan Richard and Andrés Finzi
Viruses 2024, 16(7), 1167; https://doi.org/10.3390/v16071167 - 20 Jul 2024
Cited by 1 | Viewed by 1474
Abstract
Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion [...] Read more.
Natural Killer (NK) cells have the potential to eliminate HIV-1-infected cells by antibody-dependent cellular cytotoxicity (ADCC). NK cell activation is tightly regulated by the engagement of its inhibitory and activating receptors. The activating receptor CD16 drives ADCC upon binding to the Fc portion of antibodies; NK cell activation is further sustained by the co-engagement of activating receptors NTB-A and 2B4. During HIV-1 infection, Nef and Vpu accessory proteins contribute to ADCC escape by downregulating the ligands of NTB-A and 2B4. HIV-1 also evades ADCC by keeping its envelope glycoproteins (Env) in a “closed” conformation which effectively masks epitopes recognized by non-neutralizing antibodies (nnAbs) which are abundant in the plasma of people living with HIV. To achieve this, the virus uses its accessory proteins Nef and Vpu to downregulate the CD4 receptor, which otherwise interacts with Env and exposes the epitopes recognized by nnAbs. Small CD4-mimetic compounds (CD4mc) have the capacity to expose these epitopes, thus sensitizing infected cells to ADCC. Given the central role of NK cell co-activating receptors NTB-A and 2B4 in Fc-effector functions, we studied their contribution to CD4mc-mediated ADCC. Despite the fact that their ligands are partially downregulated by HIV-1, we found that both co-activating receptors significantly contribute to CD4mc sensitization of HIV-1-infected cells to ADCC. Full article
(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)
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11 pages, 4842 KiB  
Article
Cytokine Response of Natural Killer Cells to Hepatitis B Virus Infection Depends on Monocyte Co-Stimulation
by Paul Kupke, Johanna Brucker, Jochen M. Wettengel, Ulrike Protzer, Jürgen J. Wenzel, Hans J. Schlitt, Edward K. Geissler and Jens M. Werner
Viruses 2024, 16(5), 741; https://doi.org/10.3390/v16050741 - 8 May 2024
Viewed by 1815
Abstract
Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal [...] Read more.
Hepatitis B virus (HBV) is a major driver of chronic hepatic inflammation, which regularly leads to liver cirrhosis or hepatocellular carcinoma. Immediate innate immune cell response is crucial for the rapid clearance of the infection. Here, natural killer (NK) cells play a pivotal role in direct cytotoxicity and the secretion of antiviral cytokines as well as regulatory function. The aim of this study was to further elucidate NK cell responses triggered by an HBV infection. Therefore, we optimized HBV in vitro models that reliably stimulate NK cells using hepatocyte-like HepG2 cells expressing the Na+-taurocholate co-transporting polypeptide (NTCP) and HepaRG cells. Immune cells were acquired from healthy platelet donors. Initially, HepG2-NTCP cells demonstrated higher viral replication compared to HepaRG cells. Co-cultures with immune cells revealed increased production of interferon-γ and tumor necrosis factor-α by NK cells, which was no longer evident in isolated NK cells. Likewise, the depletion of monocytes and spatial separation from target cells led to the absence of the antiviral cytokine production of NK cells. Eventually, the combined co-culture of isolated NK cells and monocytes led to a sufficient cytokine response of NK cells, which was also apparent when communication between the two immune cell subpopulations was restricted to soluble factors. In summary, our study demonstrates antiviral cytokine production by NK cells in response to HBV+ HepG2-NTCP cells, which is dependent on monocyte bystander activation. Full article
(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)
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17 pages, 4760 KiB  
Article
Galectin-3-ITGB1 Signaling Mediates Interleukin 10 Production of Hepatic Conventional Natural Killer Cells in Hepatitis B Virus Transgenic Mice and Correlates with Hepatocellular Carcinoma Progression in Patients
by Yongyan Chen, Wendi Zhang, Min Cheng, Xiaolei Hao, Haiming Wei, Rui Sun and Zhigang Tian
Viruses 2024, 16(5), 737; https://doi.org/10.3390/v16050737 - 7 May 2024
Cited by 3 | Viewed by 1942
Abstract
Background and Aims: The outcomes of HBV infections are related to complex immune imbalances; however, the precise mechanisms by which HBV induces immune dysfunction are not well understood. Methods: HBV transgenic (HBs-Tg) mice were used to investigate intrahepatic NK cells in two distinct [...] Read more.
Background and Aims: The outcomes of HBV infections are related to complex immune imbalances; however, the precise mechanisms by which HBV induces immune dysfunction are not well understood. Methods: HBV transgenic (HBs-Tg) mice were used to investigate intrahepatic NK cells in two distinct subsets: conventional NK (cNK) and liver-resident NK (LrNK) cells during a chronic HBV infection. Results: The cNK cells, but not the LrNK cells, were primarily responsible for the increase in the number of bulk NK cells in the livers of ageing HBs-Tg mice. The hepatic cNK cells showed a stronger ability to produce IL-10, coupled with a higher expression of CD69, TIGIT and PD-L1, and lower NKG2D expression in ageing HBs-Tg mice. A lower mitochondrial mass and membrane potential, and less polarized localization were observed in the hepatic cNK cells compared with the splenic cNK cells in the HBs-Tg mice. The enhanced galectin-3 (Gal-3) secreted from HBsAg+ hepatocytes accounted for the IL-10 production of hepatic cNK cells via ITGB1 signaling. For humans, LGALS3 and ITGB1 expression is positively correlated with IL-10 expression, and negatively correlated with the poor clinical progression of HCC. Conclusions: Gal-3-ITGB1 signaling shapes hepatic cNK cells but not LrNK cells during a chronic HBV infection, which may correlate with HCC progression. Full article
(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)
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Review

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15 pages, 2014 KiB  
Review
Emerging Insights into Memory Natural Killer Cells and Clinical Applications
by Jonida Kokiçi, Anucha Preechanukul, Helena Arellano-Ballestero, Frances Gorou and Dimitra Peppa
Viruses 2024, 16(11), 1746; https://doi.org/10.3390/v16111746 - 7 Nov 2024
Cited by 1 | Viewed by 2049
Abstract
Natural killer (NK) cells are innate lymphocytes that can rapidly mount a response to their targets by employing diverse mechanisms. Due to their functional attributes, NK cells have been implicated in anti-viral and anti-tumour immune responses. Although traditionally known to mount non-specific, rapid [...] Read more.
Natural killer (NK) cells are innate lymphocytes that can rapidly mount a response to their targets by employing diverse mechanisms. Due to their functional attributes, NK cells have been implicated in anti-viral and anti-tumour immune responses. Although traditionally known to mount non-specific, rapid immune responses, in recent years, the notion of memory NK cells with adaptive features has gained more recognition. Memory NK cells emerge in response to different stimuli, such as viral antigens and specific cytokine combinations. They form distinct populations, accompanied by transcriptional, epigenetic and metabolic reprogramming, resulting in unique phenotypic and functional attributes. Several clinical trials are testing the efficacy of memory NK cells due to their enhanced functionality, bioenergetic profile and persistence in vivo. The therapeutic potential of NK cells is being harnessed in viral infections, with wider applications in the cancer field. In this review, we summarise the current state of research on the generation of memory NK cells, along with their clinical applications in viral infection and cancer. Full article
(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)
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20 pages, 1267 KiB  
Review
The Role of Natural Killer Cells and Their Metabolism in HIV-1 Infection
by Kewreshini K. Naidoo and Marcus Altfeld
Viruses 2024, 16(10), 1584; https://doi.org/10.3390/v16101584 - 9 Oct 2024
Cited by 1 | Viewed by 2450
Abstract
Natural killer (NK) cells are multifaceted innate effector cells that critically influence antiviral immunity, and several protective NK cell features that modulate HIV-1 acquisition and viral control have been described. Chronic HIV-1 infection leads to NK cell impairment that has been associated with [...] Read more.
Natural killer (NK) cells are multifaceted innate effector cells that critically influence antiviral immunity, and several protective NK cell features that modulate HIV-1 acquisition and viral control have been described. Chronic HIV-1 infection leads to NK cell impairment that has been associated with metabolic dysregulations. Therapeutic approaches targeting cellular immune metabolism represent potential novel interventions to reverse defective NK cell function in people living with HIV. Full article
(This article belongs to the Special Issue Natural Killer Cell in Viral Infection)
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