Myeloid infection links epithelial and B cell tropisms of Murid Herpesvirus-4

Frederico, Bruno, Milho, Rrcardo, May, Janet S., Gillet, Laurent and Stevenson, Philip G. (2012) Myeloid infection links epithelial and B cell tropisms of Murid Herpesvirus-4. PLoS Pathogens, 8 9: e1002935-e1002935. doi:10.1371/journal.ppat.1002935

Author Frederico, Bruno
Milho, Rrcardo
May, Janet S.
Gillet, Laurent
Stevenson, Philip G.
Title Myeloid infection links epithelial and B cell tropisms of Murid Herpesvirus-4
Journal name PLoS Pathogens   Check publisher's open access policy
ISSN 1553-7366
Publication date 2012-09
Year available 2012
Sub-type Article (original research)
DOI 10.1371/journal.ppat.1002935
Open Access Status DOI
Volume 8
Issue 9
Start page e1002935
End page e1002935
Total pages 14
Place of publication San Francisco, CA United States
Publisher Public Library of Science
Collection year 2012
Language eng
Formatted abstract
Gamma-herpesviruses persist in lymphocytes and cause disease by driving their proliferation. Lymphocyte infection is therefore a key pathogenetic event. Murid Herpesvirus-4 (MuHV-4) is a rhadinovirus that like the related Kaposi's Sarcoma-associated Herpesvirus persists in B cells in vivo yet infects them poorly in vitro. Here we used MuHV-4 to understand how virion tropism sets the path to lymphocyte colonization. Virions that were highly infectious in vivo showed a severe post-binding block to B cell infection. Host entry was accordingly an epithelial infection and B cell infection a secondary event. Macrophage infection by cell-free virions was also poor, but improved markedly when virion binding improved or when macrophages were co-cultured with infected fibroblasts. Under the same conditions B cell infection remained poor; it improved only when virions came from macrophages. This reflected better cell penetration and correlated with antigenic changes in the virion fusion complex. Macrophages were seen to contact acutely infected epithelial cells, and cre/lox-based virus tagging showed that almost all the virus recovered from lymphoid tissue had passed through lysM+ and CD11c+ myeloid cells. Thus MuHV-4 reached B cells in 3 distinct stages: incoming virions infected epithelial cells; infection then passed to myeloid cells; glycoprotein changes then allowed B cell infection. These data identify new complexity in rhadinovirus infection and potentially also new vulnerability to intervention.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 18 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 23 Mar 2015, 11:20:34 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences