NDLI: NK Cell and Ig Interplay in Defense against Herpes Simplex Virus Type 1: Epistatic Interaction of CD16A and IgG1 Allotypes of Variable Affinities Modulates Antibody-Dependent Cellular Cytotoxicity and Susceptibility to Clinical Reactivation.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	López-Botet, Miguel Portero, Francisca Muntasell, Aura Moraru, Manuela Reyburn, Hugh T. Black, Laurel E. Pandey, Janardan P. Vilches, Carlos
Description	Author Affiliation: Moraru M ( Inmunogenética e Histocompatibilidad, Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Madrid, Spain); Black LE ( Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425); Muntasell A ( Institut Hospital del Mar d'Investigaciones Médiques, 08002 Barcelona, Spain); Portero F ( Servicio de Microbiología, Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Madrid, Spain); López-Botet M ( Institut Hospital del Mar d'Investigaciones Médiques, 08002 Barcelona, Spain); Reyburn HT ( Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas, 28049 Madrid, Spain.); Pandey JP ( Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425); Vilches C ( Inmunogenética e Histocompatibilidad, Instituto de Investigación Sanitaria Puerta de Hierro, 28222 Majadahonda, Madrid, Spain)
Abstract	HSV-1 latently infects most humans, causing a variable clinical picture that depends, in part, on host genetic factors. Both IgG and its cellular FcRs, CD16A and CD32A-C (encoded by FCGR3A and FCGR2A-C, respectively, on chromosome 1), display polymorphisms that could affect their defensive function. Of potential relevance are a FCGR3A dimorphism resulting in CD16A-valine/phenylalanine-158 allotypes with different IgG affinity, variations conditioning NK cell expression of CD32B or CD32C, and IgG1 H chain (IGHG1) and kappa-chain (IGKC) polymorphisms determining allotypes designated G1m and Km. In this study, we assessed the contribution of Ig genetic variations and their interaction with FcR polymorphism to HSV-1 susceptibility, as well as their impact on NK cell-mediated Ab-dependent cellular cytotoxicity (ADCC). Our results show an epistatic interaction between IGHG1 and FCGR3A such that the higher affinity CD16A-158V/V genotype associates with an asymptomatic course of HSV-1 infection only in homozygotes for G1m3. Furthermore, CD16A-158V and G1m3 allotypes enhanced ADCC against opsonized HSV-1-infected fibroblasts. Conversely, Km allotypes and CD32B or CD32C expression on NK cells did not significantly influence HSV-1 susceptibility or ADCC. NK cells degranulating against immune serum-opsonized HSV-1-infected fibroblasts had heterogeneous phenotypes. Yet, enhanced ADCC was observed among NK cells showing a differentiated, memory-like phenotype (NKG2C(bright)NKG2A(-)CD57(+)FcRÎ³(-)), which expand in response to human CMV. These results extend our knowledge on the importance of immunogenetic polymorphisms and NK cell-Ab interplay in the host response against HSV-1 and point to the relevance of interactions between immune responses elicited during chronic coinfection by multiple herpesviruses.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	195
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Herpes Simplex Immunology Herpesvirus 1, Human Immunoglobulin G Killer Cells, Natural Animals Antibody-dependent Cell Cytotoxicity Genetics Cell Degranulation Cell Line Disease Susceptibility Epistasis, Genetic Gene Expression Genetic Variation Genotype Immunoglobulin Heavy Chains Immunoglobulin Kappa-chains Immunophenotyping Phenotype Polymorphism, Genetic Receptors, Igg Metabolism Virus Activation Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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