Killing of Avian and Swine Influenza Virus by Natural Killer Cells (cid:1)

Today, global attention is focused on two influenza virus strains: the current pandemic strain, swine origin influenza virus (H1N1-2009), and the highly pathogenic avian influenza virus, H5N1. At present, the infection caused by the H1N1-2009 is moderate, with mortality rates of less <1%. In contrast, infection with the H5N1 virus resulted in high mortality rates, and ca. 60% of the infected patients succumb to the infection. Thus, one of the world greatest concerns is that the H5N1 virus will evolve to allow an efficient human infection and human-to-human transmission. Natural killer (NK) cells are one of the innate immune components playing an important role in fighting against influenza viruses. One of the major NK activating receptors involved in NK cell cytotoxicity is NKp46. We previously demonstrated that NKp46 recognizes the hemagglutinin proteins of B and A influenza virus strains. Whether NKp46 could also interact with H1N1-2009 virus or with the avian influenza virus is still unknown. We analyzed the immunological properties of both the avian and the H1N1-2009 influenza viruses. We show that NKp46 recognizes the hemagglutinins of H1N1-2009 and H5 and that this recognition leads to virus killing both in vitro and in vivo . However, importantly, while the swine H1-NKp46 interactions lead to the direct killing of the infected cells, the H5-NKp46 interactions were unable to elicit direct killing, probably because the NKp46 binding sites for these two viruses are different.

[1]  Marion Koopmans,et al.  Pathogenesis and Transmission of Swine-Origin 2009 A(H1N1) Influenza Virus in Ferrets , 2009, Science.

[2]  Eric Vivier,et al.  The B7 family member B7-H6 is a tumor cell ligand for the activating natural killer cell receptor NKp30 in humans , 2009, The Journal of experimental medicine.

[3]  M. Pappaioanou.  Highly pathogenic H5N1 avian influenza virus: cause of the next pandemic? , 2009, Comparative immunology, microbiology and infectious diseases.

[4]  Rahul Raman,et al.  Transmission and Pathogenesis of Swine-Origin 2009 A(H1N1) Influenza Viruses in Ferrets and Mice , 2009, Science.

[5]  Gabriele Neumann,et al.  Emergence and pandemic potential of swine-origin H1N1 influenza virus , 2009, Nature.

[6]  A. Arnold,et al.  Activation of Natural Killer Cells by Newcastle Disease Virus Hemagglutinin-Neuraminidase , 2009, Journal of Virology.

[7]  Hui Zeng,et al.  Pathogenesis of emerging avian influenza viruses in mammals and the host innate immune response , 2008, Immunological reviews.

[8]  I. Wilson,et al.  Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity. , 2008, Journal of molecular biology.

[9]  H. Achdout,et al.  Influenza Virus Infection Augments NK Cell Inhibition through Reorganization of Major Histocompatibility Complex Class I Proteins , 2008, Journal of Virology.

[10]  O. Mandelboim,et al.  The unique properties of human NK cells in the uterine mucosa. , 2008, Placenta.

[11]  Yingying Chen,et al.  Prostaglandin D2 Suppresses Human NK Cell Function via Signaling through D Prostanoid Receptor1 , 2007, The Journal of Immunology.

[12]  Hanah Margalit,et al.  Host Immune System Gene Targeting by a Viral miRNA , 2007, Science.

[13]  Peter Parham,et al.  NKp46 and NKG2D Recognition of Infected Dendritic Cells Is Necessary for NK Cell Activation in the Human Response to Influenza Infection1 , 2007, The Journal of Immunology.

[14]  Y. Kawaoka,et al.  Strategies for developing vaccines against H5N1 influenza A viruses. , 2006, Trends in molecular medicine.

[15]  O. Mandelboim,et al.  Tumor and viral recognition by natural killer cells receptors. , 2006, Seminars in cancer biology.

[16]  Thijs Kuiken,et al.  H5N1 Virus Attachment to Lower Respiratory Tract , 2006, Science.

[17]  Ian A. Wilson,et al.  Structure and Receptor Specificity of the Hemagglutinin from an H5N1 Influenza Virus , 2006, Science.

[18]  Angel Porgador,et al.  Lethal influenza infection in the absence of the natural killer cell receptor gene Ncr1 , 2006, Nature Immunology.

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

[20]  E. D. Kilbourne.  Influenza Pandemics of the 20th Century , 2006, Emerging infectious diseases.

[21]  Ofer Levi,et al.  Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus , 2005, Nature Immunology.

[22]  Z. Grossman,et al.  Evaluation of a Multiplex Real-Time Reverse Transcriptase PCR Assay for Detection and Differentiation of Influenza Viruses A and B during the 2001-2002 Influenza Season in Israel , 2005, Journal of Clinical Microbiology.

[23]  I. Julkunen,et al.  Cytokine and contact-dependent activation of natural killer cells by influenza A or Sendai virus-infected macrophages. , 2004, The Journal of general virology.

[24]  W. Yokoyama,et al.  The dynamic life of natural killer cells. , 2004, Annual review of immunology.

[25]  Angel Porgador,et al.  The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46. , 2004, Blood.

[26]  P. Sun,et al.  Crystal Structure of the Human Natural Killer (NK) Cell Activating Receptor NKp46 Reveals Structural Relationship to Other Leukocyte Receptor Complex Immunoreceptors* , 2003, Journal of Biological Chemistry.

[27]  D. Raulet.  Roles of the NKG2D immunoreceptor and its ligands , 2003, Nature Reviews Immunology.

[28]  H. Achdout,et al.  Enhanced Recognition of Human NK Receptors After Influenza Virus Infection1 , 2003, The Journal of Immunology.

[29]  Adelheid Cerwenka,et al.  Natural killer cells, viruses and cancer , 2001, Nature Reviews Immunology.

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

[31]  C. Sutherland,et al.  The UL16‐binding proteins, a novel family of MHC class I‐related ligands for NKG2D, activate natural killer cell functions , 2001, Immunological reviews.

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

[33]  O. Mandelboim,et al.  Human CD16 as a lysis receptor mediating direct natural killer cell cytotoxicity. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[34]  R. Biassoni,et al.  Molecular Cloning of NKp46: A Novel Member of the Immunoglobulin Superfamily Involved in Triggering of Natural Cytotoxicity , 1998, The Journal of experimental medicine.

[35]  W. Yokoyama.  Natural killer cell receptors. , 1998, Current opinion in immunology.

[36]  O. Mandelboim,et al.  Protection from lysis by natural killer cells of group 1 and 2 specificity is mediated by residue 80 in human histocompatibility leukocyte antigen C alleles and also occurs with empty major histocompatibility complex molecules , 1996, The Journal of experimental medicine.

[37]  C. Scholtissek,et al.  Source for influenza pandemics , 1994, European Journal of Epidemiology.

[38]  Eric O Long,et al.  Synergy among receptors on resting NK cells for the activation of natural cytotoxicity and cytokine secretion. , 2006, Blood.

[39]  R. Biassoni,et al.  Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis. , 2001, Annual review of immunology.