In the core network derived from the overlap of all five herpesviruses, mCMV M51, and its orthologs HSV-1 UL33, VZV ORF 25, EBV BFRF4 and KSHV ORF 67.5, show up as intraviral hubs with a number of conserved interactions. For instance, the interaction between M51 and M53 was observed in all species apart from HSV-1. Interestingly, when retesting UL33 interactions under more stringent conditions (Figure S12) , the corresponding interaction between UL33 and the M53 ortholog in HSV-1, UL31, is clearly one of the positive interactions on both 2.5 and 5 mM 3AT. These interactions were not included in the HSV interactome to prevent an overrepresentation of interactions tested more than once. While not much is known about M51, M53 has been extensively documented to be involved in nuclear egress through its binding to M50 [35, 38, 49, 50] . The interaction between M53 and M50 was confirmed in this study in four viruses. In addition, from our study of interactions in VZV we observed an association between the ortholog of M51 (ORF25) with the M50 ortholog (ORF24) [23] , and retesting of HSV-1 UL33 interactions also revealed its binding to HSV-1 UL34 lacking the transmembrane region ( Figure S12 ). Finally, immunofluorescense studies indicated that M51 co-localizes with both M53 and M50 when using fluorescent fusion proteins. These results suggest a possible role for M51 in nuclear egress through its interactions with M53 and/or M50. As interactions between orthologs of M51 and M53 were observed in members of all three subfamilies, it is likely that this represents a conserved function of M51. Previous studies have indicated that the M51 ortholog in HSV-1 (UL33) is involved in packaging of DNA [51] , and that it interacts with at least one of the subunits of the terminase complex (UL28) [52] . In the data presented here, UL33 was observed to interact with UL15 and UL28 in three different species. These results suggest that UL33 represents an association between packaging and egress. Studies done in HSV-1 have indicated that UL33 is associated with the external surface of capsids [53] , which would make such a dual role reasonable. While it is not known exactly how UL33 associates with the capsid, the interaction observed between M51 and the smallest capsid protein (m48.2) in mCMV and EBV suggests a possible manner of association.