Reference : An essential role for gamma-herpesvirus latency-associated nuclear antigen homolog in...
Scientific journals : Article
Life sciences : Veterinary medicine & animal health
http://hdl.handle.net/2268/148679
An essential role for gamma-herpesvirus latency-associated nuclear antigen homolog in an acute lymphoproliferative disease of cattle.
English
Palmeira, Leonor mailto [Université de Liège > Département de productions animales > GIGA-R : Génomique animale >]
Sorel, Océane mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Van Campe, Willem [> >]
Boudry, Christel mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Roels, Stefan [> >]
Myster, Françoise mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Reschner, Anca [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Coulie, Pierre G. [> >]
Kerkhofs, Pierre [> >]
Vanderplasschen, Alain mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
Dewals, Benjamin G mailto [Université de Liège - ULiège > > Immunologie et vaccinologie >]
29-Apr-2013
Proceedings of the National Academy of Sciences of the United States of America
National Academy of Sciences
Yes (verified by ORBi)
International
0027-8424
1091-6490
Washington
DC
[en] Wildebeests carry asymptomatically alcelaphine herpesvirus 1 (AlHV-1), a gamma-herpesvirus inducing malignant catarrhal fever (MCF) to several ruminant species (including cattle). This acute and lethal lymphoproliferative disease occurs after a prolonged asymptomatic incubation period after transmission. Our recent findings with the rabbit model indicated that AlHV-1 infection is not productive during MCF. Here, we investigated whether latency establishment could explain this apparent absence of productive infection and sought to determine its role in MCF pathogenesis. First, whole-genome cellular and viral gene expression analyses were performed in lymph nodes of MCF-developing calves. Whereas a severe disruption in cellular genes was observed, only 10% of the entire AlHV-1 genome was expressed, contrasting with the 45% observed during productive infection in vitro. In vivo, the expressed viral genes included the latency-associated nuclear antigen homolog ORF73 but none of the regions known to be essential for productive infection. Next, genomic conformation analyses revealed that AlHV-1 was essentially episomal, further suggesting that MCF might be the consequence of a latent infection rather than abortive lytic infection. This hypothesis was further supported by the high frequencies of infected CD8+ T cells during MCF using immunodetection of ORF73 protein and single-cell RT-PCR approaches. Finally, the role of latency-associated ORF73 was addressed. A lack of ORF73 did not impair initial virus replication in vivo, but it rendered AlHV-1 unable to induce MCF and persist in vivo and conferred protection against a lethal challenge with a WT virus. Together, these findings suggest that a latent infection is essential for MCF induction.
http://hdl.handle.net/2268/148679
10.1073/pnas.1216531110

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