Publication Database

Marek's disease viral interleukin-8 promotes lymphoma formation through targeted recruitment of B cells and CD4+ CD25+ T cells (2012)

Art

Zeitschriftenartikel / wissenschaftlicher Beitrag

Autoren

Engel, Annemarie T (WE 5)

Selvaraj, Ramesh K

Kamil, Jeremy P

Osterrieder, Nikolaus (WE 5)

Kaufer, Benedikt B (WE 5)

Quelle

Journal of virology : publ. by the American Society for Microbiology

Bandzählung: 86

Heftzählung: 16

Seiten: 8536 – 8545

ISSN: 1098-5514

Sprache

Englisch

Verweise

DOI: 10.1128/JVI.00556-12

Pubmed: 22647701

Kontakt

Institut für Virologie

Robert-von-Ostertag-Str. 7-13
14163 Berlin
+49 30 838 51833
virologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Marek's disease virus (MDV) is a cell-associated and highly oncogenic alphaherpesvirus that infects chickens. During lytic and latent MDV infection, a CXC chemokine termed viral interleukin-8 (vIL-8) is expressed. Deletion of the entire vIL-8 open reading frame (ORF) was shown to severely impair disease progression and tumor development; however, it was unclear whether this phenotype was due to loss of secreted vIL-8 or of splice variants that fuse exons II and III of vIL-8 to certain upstream open reading frames, including the viral oncoprotein Meq. To specifically examine the role of secreted vIL-8 in MDV pathogenesis, we constructed a recombinant virus, vΔMetvIL-8, in which we deleted the native start codon from the signal peptide encoding exon I. This mutant lacked secreted vIL-8 but did not affect Meq-vIL-8 splice variants. Loss of secreted vIL-8 resulted in highly reduced disease and tumor incidence in animals infected with vΔMetvIL-8 by the intra-abdominal route. Although vΔMetvIL-8 was still able to spread to naïve animals by the natural route, infection and lymphomagenesis in contact animals were severely impaired. In vitro assays showed that purified recombinant vIL-8 efficiently binds to and induces chemotaxis of B cells, which are the main target for lytic MDV replication, and also interacts with CD4(+) CD25(+) T cells, known targets of MDV transformation. Our data provide evidence that vIL-8 attracts B and CD4(+) CD25(+) T cells to recruit targets for both lytic and latent infection.