The Tegument Protein pUL47 of Marek's Disease Virus Is Necessary for Horizontal Transmission and Is Important for Expression of Glycoprotein gC.

Viral tropism and transmission of herpesviruses are best studied in their natural host for maximal biological relevance. In the case of alphaherpesviruses, few reports have focused on those aspects, primarily because of the few animal models available as natural hosts that are compatible with such studies. Here, using Marek's disease virus (MDV), a highly contagious and deadly alphaherpesvirus of chickens, we analyze the role of tegument proteins pUL47 and pUL48 in the whole life cycle of the virus. We report that a virus lacking the UL48 gene (vΔUL48) is impaired in growth in cell culture and has diminished virulence in vivo In contrast, a virus lacking UL47 (vΔUL47) is unaffected in its growth in vitro and is as virulent in vivo as the wild-type (WT) virus. Surprisingly, we observed that vΔUL47 was unable to be horizontally transmitted to naive chickens, in contrast to the WT virus. In addition, we show that pUL47 is important for the splicing of UL44 transcripts encoding glycoprotein gC, a protein known as being essential for horizontal transmission of MDV. Importantly, we observed that the levels of gC are lower in the absence of pUL47. Notably, this phenotype is similar to that of another transmission-incompetent mutant ΔUL54, which also affects the splicing of UL44 transcripts. This is the first study describing the role of pUL47 in both viral transmission and the splicing and expression of gC.IMPORTANCE Host-to-host transmission of viruses is ideally studied in vivo in the natural host. Veterinary viruses such as Marek's disease virus (MDV) are, therefore, models of choice to explore these aspects. The natural host of MDV, the chicken, is small, inexpensive, and economically important. MDV is a deadly and contagious herpesvirus that can kill infected animals in less than 4 weeks. The virus naturally infects epithelial cells of the feather follicle epithelium from where it is shed into the environment. In this study, we demonstrate that the viral protein pUL47 is an essential factor for bird-to-bird transmission of the virus. We provide some molecular basis to this function by showing that pUL47 enhances the splicing and the expression of another viral gene, UL44, which is essential for viral transmission. pUL47 may have a similar function in human herpesviruses such as varicella-zoster virus or herpes simplex viruses.