Article (Scientific journals)
Myeloid infection links epithelial and B cell tropisms of murid herpesvirus-4.
Frederico, Bruno; Milho, Ricardo; May, Janet S. et al.
2012In PLoS Pathogens, 8 (9), p. 1002935
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Abstract :
[en] 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.
Disciplines :
Microbiology
Author, co-author :
Frederico, Bruno
Milho, Ricardo
May, Janet S.
Gillet, Laurent  ;  Université de Liège - ULiège > Immunologie et vaccinologie
Stevenson, Philip G.
Language :
English
Title :
Myeloid infection links epithelial and B cell tropisms of murid herpesvirus-4.
Publication date :
2012
Journal title :
PLoS Pathogens
ISSN :
1553-7366
eISSN :
1553-7374
Publisher :
Public Library of Science, United States - California
Volume :
8
Issue :
9
Pages :
e1002935
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 27 November 2012

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