Regulation of antigen processing and presentation molecules in West Nile virus-infected human skin fibroblasts

Autor: Nicholas J. C. King, Stephanie J Arnold, Lisa M. Sedger, Sarah R. Osvath, Roy A. Hall
Rok vydání: 2004
Předmět:
viruses
Antigen-Presenting Cells
Fluorescent Antibody Technique
Human leukocyte antigen
Biology
Viral Nonstructural Proteins
Major histocompatibility complex
Immune recognition molecules
Antigen
Interferon
Kunjin virus
HLA Antigens
Virology
medicine
Humans
RNA
Messenger

ATP Binding Cassette Transporter
Subfamily B
Member 2

Antigen-presenting cell
Skin
HLA-A Antigens
Human leukocyte antigen-A
-B
-C

Antigen processing
Tumor Necrosis Factor-alpha
Reverse Transcriptase Polymerase Chain Reaction
Flavivirus
ATP-Binding Cassette Sub-Family B Member 2
Antibodies
Monoclonal

Interferon-beta
Low molecular weight polypeptide
Fibroblasts
biology.organism_classification
Fluoresceins
Molecular biology
Immunohistochemistry
Tumor necrosis factor-α
Cysteine Endopeptidases
biology.protein
ATP-Binding Cassette Transporters
Transporter associated with antigen presentation
West Nile virus
West Nile Fever
medicine.drug
Popis: Infection of humans with the West Nile flavivirus principally occurs via tick and mosquito bites. Here, we document the expression of antigen processing and presentation molecules in West Nile virus (WNV)-infected human skin fibroblast (HFF) cells. Using a new Flavivirus-specific antibody, 4G4, we have analyzed cell surface human leukocyte antigen (HLA) expression on virus-infected cells at a single cell level. Using this approach, we show that West Nile Virus infection alters surface HLA expression on both infected HFF and neighboring uninfected HFF cells. Interestingly, increased surface HLA evident on infected HFF cultures is almost entirely due to virus-induced interferon (IFN)α/β because IFNα/β-neutralizing antibodies completely prevent increased surface HLA expression. In contrast, RT-PCR analysis indicates that WNV infection results in increased mRNAs for HLA-A, -B, and -C genes, and HLA-associated molecules low molecular weight polypeptide-2 (LMP-2) and transporter associated with antigen presentation-1 (TAP-1), but induction of these mRNAs is not diminished in HFF cells cultured with IFNα/β- neutralizing antibodies. Taken together, these data support the idea that that both cytokine-dependent and cytokine-independent mechanisms account for WNV-induced HLA expression in human skin fibroblasts. © 2004 Elsevier Inc. All rights reserved.
Databáze: OpenAIRE