PMID- 15207616 OWN - NLM STAT- MEDLINE DCOM- 20040730 LR - 20220317 IS - 0042-6822 (Print) IS - 0042-6822 (Linking) VI - 324 IP - 2 DP - 2004 Jul 1 TI - Regulation of antigen processing and presentation molecules in West Nile virus-infected human skin fibroblasts. PG - 286-96 AB - 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)alpha/beta because IFNalpha/beta-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 IFNalpha/beta-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. FAU - Arnold, Stephanie J AU - Arnold SJ AD - Centre for Virus Research, Westmead Millennium Institute, Department of Medicine, The University of Sydney, Westmead, Sydney, NSW 2145, Australia. FAU - Osvath, Sarah R AU - Osvath SR FAU - Hall, Roy A AU - Hall RA FAU - King, Nicholas J C AU - King NJ FAU - Sedger, Lisa M AU - Sedger LM LA - eng PT - Comparative Study PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Virology JT - Virology JID - 0110674 RN - 0 (ATP Binding Cassette Transporter, Subfamily B, Member 2) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Antibodies, Monoclonal) RN - 0 (Fluoresceins) RN - 0 (HLA Antigens) RN - 0 (HLA-A Antigens) RN - 0 (RNA, Messenger) RN - 0 (TAP1 protein, human) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (Viral Nonstructural Proteins) RN - 0 (fluorescein carboxylate) RN - 144416-78-4 (LMP-2 protein) RN - 77238-31-4 (Interferon-beta) RN - EC 3.4.22.- (Cysteine Endopeptidases) SB - IM MH - ATP Binding Cassette Transporter, Subfamily B, Member 2 MH - ATP-Binding Cassette Transporters/biosynthesis/genetics MH - Antibodies, Monoclonal MH - Antigen-Presenting Cells/*immunology MH - Cysteine Endopeptidases/biosynthesis/genetics MH - Fibroblasts/*immunology/virology MH - Fluoresceins MH - Fluorescent Antibody Technique MH - HLA Antigens/analysis/*biosynthesis/genetics MH - HLA-A Antigens/biosynthesis/genetics MH - Humans MH - Immunohistochemistry MH - Interferon-beta/analysis/biosynthesis MH - RNA, Messenger/analysis/biosynthesis MH - Reverse Transcriptase Polymerase Chain Reaction MH - Skin MH - Tumor Necrosis Factor-alpha/analysis/biosynthesis MH - Viral Nonstructural Proteins/*analysis/immunology MH - West Nile Fever/*immunology/virology MH - West Nile virus/growth & development/*immunology EDAT- 2004/06/23 05:00 MHDA- 2004/07/31 05:00 CRDT- 2004/06/23 05:00 PHST- 2004/01/06 00:00 [received] PHST- 2004/03/02 00:00 [revised] PHST- 2004/03/29 00:00 [accepted] PHST- 2004/06/23 05:00 [pubmed] PHST- 2004/07/31 05:00 [medline] PHST- 2004/06/23 05:00 [entrez] AID - S0042682204002235 [pii] AID - 10.1016/j.virol.2004.03.036 [doi] PST - ppublish SO - Virology. 2004 Jul 1;324(2):286-96. doi: 10.1016/j.virol.2004.03.036.