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Abstract

We used knockout recombinant viruses to examine the functions of the M81 tegument proteins. It has recently been shown that functions of EBV proteins and of some EBV non-coding RNAs differ between the EBV M81 and B95.8 strains. EBV M81 strain has the unique feature to show a spontaneous lytic replication within B cells. In particular, this allows for an easy investigation without addition of chemical agents or artificial induction of the virus replication to the cells. The first part of our work underscored the importance of tegument proteins for an efficient virus production and for the infectivity of the produced viruses. We then found that the deletion of BGLF4 does not block production of virus and transmission across B cells but only reduces it on average three times. This suggests that the effects of the deletion are less pronounced than in 293 producer cells in which the absence of BGLF4 reduces the efficiency of transmission by a factor 30. Altogether, the effect of BGLF4 deletion affected lytic replication and propagation only mildly, suggesting that the multiple effects in the literature have little influence in the context of the whole virus. We could confirm viral targets of BGLF4 such as BMRF1 and the role of this kinase in late protein expression. However, our work has also evidenced the role of BGLF4 in B cell infection, a function that was not identified clearly before. Here the impact of BGLF4 on late gene expression through reduced binding and fusion is probably also crucial. Finally, although the BGLF4 deletion mutant virus could transform B cells normally, we found that BGLF4 surprisingly regulates the expression of latent proteins, in particular of LMP1. How a protein expressed only in lytically replicating cells can influence the expression of proteins in latently infected cells remains to be elucidated.