Comprehensive Analyses of Intraviral Epstein-Barr Virus Protein–Protein Interactions Hint Central Role of BLRF2 in the Tegument Network

Abstract

EBV remains a significant public health challenge, causing infectious mononucleosis and several cancer types. Therefore, the better understanding of the molecular mechanisms underlying EBV replication is of high clinical importance.

Tegument proteins of Epstein-Barr virus: Diverse functions, complex networks, and oncogenesis

“…Tegument proteins form a complex PPI network that attaches the viral envelope to the nucleocapsid. We prepared a simplified diagram of the EBV PPI network based on prior reports [ [20] , [21] , [22] , [23] ] ( Fig. 1 ).…”

“…Although palmitoylation of EBV BSRF1 and HCMV UL71 proteins has not been confirmed, it is likely because the modified N-terminal cysteine is conserved and associated with membranes, particularly of the Golgi apparatus [ 14 , 47 ]. EBV BSRF1 associates with many viral proteins, besides BBRF2, including gB, gH [ 40 ], gN, BLRF2 [ 22 ], and BGLF3.5 [ 14 ] ( Fig. 1 ).…”

“…BBLF1 and its counterparts are post-translationally modified by palmitoylation and myristoylation [ [54] , [55] , [56] ]. BBLF1 is a small protein, which interacts with BNRF1, gH and gp350 [ [20] , [21] , [22] ]. BGLF2 associates with BBRF2, BKRF4, and gB ( Fig.…”

“…BGLF2 associates with BBRF2, BKRF4, and gB ( Fig. 1 ) [ 21 , 22 , 48 , 57 ]. HSV UL11 binds with gE [ 58 ], and UL16 binds to gE [ 59 ], UL49 [ 60 ], UL7 [ 21 ], UL21 [ 61 ], and UL35 (small capsid) [ 21 ] ( Fig.…”

“…In EBV, the loss of these tegument proteins can be compensated for by gamma-herpesvirus-specific proteins, BKRF4, BNRF1, and BLRF2. BKRF4 is linked to BGLF2, BLRF2, BOLF1, BNRF1, and gN [ 22 , 41 , 57 ]. BNRF1 interacts with tegument proteins, BKRF4, BBLF1, and BLRF2, and possibly BFRF3 (small capsid) [ [20] , [21] , [22] ].…”