Reference : Myeloid infection links epithelial and B cell tropisms of murid herpesvirus-4.
Scientific journals : Article
Life sciences : Microbiology
http://hdl.handle.net/2268/135277
Myeloid infection links epithelial and B cell tropisms of murid herpesvirus-4.
English
Frederico, Bruno [> >]
Milho, Ricardo [> >]
May, Janet S. [> >]
Gillet, Laurent mailto [Université de Liège - ULg > > Immunologie et vaccinologie >]
Stevenson, Philip G. [> >]
2012
PLoS Pathogens
8
9
e1002935
Yes
International
1553-7366
1553-7374
United States
[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.
http://hdl.handle.net/2268/135277
10.1371/journal.ppat.1002935

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