Viral Infection of Human Natural Killer Cells

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.

[1]  Oliver Wicht,et al.  Respiratory Syncytial Virus Infects Primary Neonatal and Adult Natural Killer Cells and Affects Their Antiviral Effector Function , 2018, The Journal of infectious diseases.

[2]  B. Slobedman,et al.  Varicella zoster virus productively infects human natural killer cells and manipulates phenotype , 2018, PLoS pathogens.

[3]  Y. Lau,et al.  Avian influenza virus directly infects human natural killer cells and inhibits cell activity , 2017, Virologica Sinica.

[4]  M. Degli-Esposti,et al.  “Natural Regulators”: NK Cells as Modulators of T Cell Immunity , 2016, Front. Immunol..

[5]  J. McLinden,et al.  Human Pegivirus (HPgV; formerly known as GBV-C) inhibits IL-12 dependent natural killer cell function. , 2015, Virology.

[6]  M. Winters,et al.  Human pegivirus RNA is found in multiple blood mononuclear cells in vivo and serum-derived viral RNA-containing particles are infectious in vitro. , 2014, The Journal of general virology.

[7]  A. Helenius,et al.  Host Cell Entry of Respiratory Syncytial Virus Involves Macropinocytosis Followed by Proteolytic Activation of the F Protein , 2013, PLoS pathogens.

[8]  M. Rowe,et al.  Epstein-Barr Virus and the Pathogenesis of T and NK Lymphoma: a Mystery Unsolved , 2012, Current Hematologic Malignancy Reports.

[9]  R. Sun,et al.  Lung natural killer cells in mice: phenotype and response to respiratory infection , 2012, Immunology.

[10]  A. Helenius,et al.  Gulping rather than sipping: macropinocytosis as a way of virus entry. , 2012, Current opinion in microbiology.

[11]  Tzou-Yien Lin,et al.  Effect of influenza A infection on umbilical cord blood natural killer function regulation with interleukin-15. , 2012, The Journal of infectious diseases.

[12]  R. Sun,et al.  Natural Killer Cells Are Involved in Acute Lung Immune Injury Caused by Respiratory Syncytial Virus Infection , 2011, Journal of Virology.

[13]  M. Smyth,et al.  Activating and inhibitory receptors of natural killer cells , 2011, Immunology and cell biology.

[14]  Bali Pulendran,et al.  Analysis of in vivo dynamics of influenza virus infection in mice using a GFP reporter virus , 2010, Proceedings of the National Academy of Sciences.

[15]  J. Peiris,et al.  Inhibition of Human Natural Killer Cell Activity by Influenza Virions and Hemagglutinin , 2010, Journal of Virology.

[16]  Yan Zhou,et al.  The functional impairment of natural killer cells during influenza virus infection , 2009, Immunology and cell biology.

[17]  L. Avendaño,et al.  Impaired Immune Response in Severe Human Lower Tract Respiratory Infection by Respiratory Syncytial Virus , 2009, The Pediatric infectious disease journal.

[18]  Y. Lau,et al.  Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis , 2009, Journal of Virology.

[19]  J. Orange,et al.  Immune dysregulation in severe influenza , 2009, Journal of leukocyte biology.

[20]  J. Zack,et al.  CD4+ NK cells can be productively infected with HIV, leading to downregulation of CD4 expression and changes in function. , 2009, Virology.

[21]  M. Degli-Esposti,et al.  Killers and beyond: NK‐cell‐mediated control of immune responses , 2008, European journal of immunology.

[22]  Eric Vivier,et al.  Functions of natural killer cells , 2008, Nature Immunology.

[23]  A. Helenius,et al.  Vaccinia Virus Uses Macropinocytosis and Apoptotic Mimicry to Enter Host Cells , 2008, Science.

[24]  F. Geissmann,et al.  The trafficking of natural killer cells , 2007, Immunological reviews.

[25]  H. Harada,et al.  Proliferative activation up‐regulates expression of CD4 and HIV‐1 co‐receptors on NK cells and induces their infection with HIV‐1 , 2007, European journal of immunology.

[26]  R. Lechler,et al.  Intercellular Transfer of MHC and Immunological Molecules: Molecular Mechanisms and Biological Significance , 2007, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[27]  Jennifer L. Reed,et al.  Severe Human Lower Respiratory Tract Illness Caused by Respiratory Syncytial Virus and Influenza Virus Is Characterized by the Absence of Pulmonary Cytotoxic Lymphocyte Responses , 2007, The Journal of infectious diseases.

[28]  L. Lanier,et al.  Natural killer cells as an initial defense against pathogens , 2006, Current Opinion in Immunology.

[29]  D. Burshtyn,et al.  Vaccinia virus modulation of natural killer cell function by direct infection. , 2006, Virology.

[30]  Yoshihiro Kawaoka,et al.  Avian flu: Influenza virus receptors in the human airway , 2006, Nature.

[31]  M. Smyth,et al.  Activation of NK cell cytotoxicity. , 2005, Molecular immunology.

[32]  J. M. Sánchez-Puig,et al.  Susceptibility of different leukocyte cell types to Vaccinia virus infection , 2004, Virology Journal.

[33]  K. Sugimoto,et al.  Epstein-Barr Virus Infection of Human Natural Killer Cell Lines and Peripheral Blood Natural Killer Cells , 2004, Cancer Research.

[34]  P. Brousset,et al.  Acquisition of Viral Receptor by NK Cells Through Immunological Synapse1 , 2003, The Journal of Immunology.

[35]  G. Pavlakis,et al.  Natural killer cells are persistently infected and resistant to direct killing by HIV-1. , 2003, Anticancer research.

[36]  Mitsuhiro Osame,et al.  Spread of HTLV-I Between Lymphocytes by Virus-Induced Polarization of the Cytoskeleton , 2003, Science.

[37]  J. Orange.  Human natural killer cell deficiencies and susceptibility to infection. , 2002, Microbes and infection.

[38]  R. Gascoyne,et al.  Evidence for Early Infection of Nonneoplastic Natural Killer Cells by Epstein-Barr Virus , 2002, Journal of Virology.

[39]  L. Kostrikis,et al.  Persistent HIV-1 infection of natural killer cells in patients receiving highly active antiretroviral therapy , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[40]  Masaharu Takahashi,et al.  TT virus is distributed in various leukocyte subpopulations at distinct levels, with the highest viral load in granulocytes. , 2002, Biochemical and biophysical research communications.

[41]  Jeffrey S. Miller.  Biology of Natural Killer Cells in Cancer and Infection , 2002, Cancer investigation.

[42]  Angel Porgador,et al.  Recognition of viral hemagglutinins by NKp44 but not by NKp30 , 2001, European journal of immunology.

[43]  Angel Porgador,et al.  Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells , 2001, Nature.

[44]  R. Longnecker,et al.  Epstein-Barr virus entry into cells. , 2000, Virology.

[45]  A. Gruhler,et al.  A comparison of viral immune escape strategies targeting the MHC class I assembly pathway , 1999, Immunological reviews.

[46]  P. Openshaw,et al.  Intracellular IFN-gamma expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection. , 1998, The Journal of general virology.

[47]  G. Srivastava,et al.  Nasal NK‐ and T‐cell lymphomas share the same type of Epstein‐Barr virus latency as nasopharyngeal carcinoma and Hodgkin's disease , 1996, International journal of cancer.

[48]  J. D'Orazio,et al.  Human natural killer (NK) cells present staphylococcal enterotoxin B (SEB) to T lymphocytes , 1996, Clinical and experimental immunology.

[49]  C A Smith,et al.  Identification and characterization of a new member of the TNF family that induces apoptosis. , 1995, Immunity.

[50]  David C. Johnson,et al.  Direct contact with herpes simplex virus-infected cells results in inhibition of lymphokine-activated killer cells because of cell-to-cell spread of virus. , 1993, The Journal of infectious diseases.

[51]  Eric O Long,et al.  Infection of natural killer cells by human herpesvirus 6 , 1993, Nature.

[52]  P. Anderson,et al.  Infection of human natural killer (NK) cells with replication-defective human T cell leukemia virus type I provirus. Increased proliferative capacity and prolonged survival of functionally competent NK cells. , 1992, Journal of immunology.

[53]  D. Scott‐Algara,et al.  Natural killer (NK) cell activity during HIV infection: a decrease in NK activity is observed at the clonal level and is not restored after in vitro long‐term culture of NK cells , 1992, Clinical and experimental immunology.

[54]  M. Rowe,et al.  Epstein-Barr viral DNA in acute large granular lymphocyte (natural killer) leukemic cells. , 1992, Blood.

[55]  B. Perussia,et al.  In vitro infection of natural killer cells with different human immunodeficiency virus type 1 isolates , 1991, Journal of virology.

[56]  M. Wainberg,et al.  Natural Killer Cell Function in Patients With Acquired Immunodeficiency Syndrome and Related Diseases , 1989, Journal of leukocyte biology.

[57]  R. Zinkernagel,et al.  Persistence of vesicular stomatitis virus in cloned interleukin-2-dependent natural killer cell lines , 1986, Journal of virology.

[58]  H. Ljunggren,et al.  Selective rejection of H–2-deficient lymphoma variants suggests alternative immune defence strategy , 1986, Nature.

[59]  G. Rice,et al.  Cytomegalovirus infects human lymphocytes and monocytes: virus expression is restricted to immediate-early gene products. , 1984, Proceedings of the National Academy of Sciences of the United States of America.

[60]  G. Rice,et al.  Viruses disrupt functions of human lymphocytes. Effects of measles virus and influenza virus on lymphocyte-mediated killing and antibody production , 1984, The Journal of experimental medicine.

[61]  L. Lanier,et al.  Natural killer cells activated in a human mixed lymphocyte response culture identified by expression of Leu-11 and class II histocompatibility antigens , 1984, The Journal of experimental medicine.

[62]  J. Streilein.  Skin-associated lymphoid tissues (SALT): origins and functions. , 1983, The Journal of investigative dermatology.

[63]  M. Kannagi,et al.  Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. , 1982, Science.

[64]  Van Kasteren.  Respiratory Syncytial Virus Infects Primary Neonatal and Adult Natural Killer Cells and Affects Their Antiviral Effector Function , 2020 .

[65]  G. Beall,et al.  Alterations in cytotoxic and phenotypic subsets of natural killer cells in acquired immune deficiency syndrome (AIDS) , 2004, Journal of Clinical Immunology.

[66]  W. Mitchell,et al.  Spontaneous and interferon resistant natural killer cell anergy in AIDS. , 1983, AIDS research.