Herpes Simplex Virus 1 ICP8 Mutant Lacking Annealing Activity Is Deficient for Viral DNA Replication
Herpes simplex virus 1 ICP8 mutant lacking annealing activity is deficient for viral DNA replication Savithri Weerasooriyaa,1, Katherine A. DiScipioa,b,1, Anthar S. Darwisha,b, Ping Baia, and Sandra K. Wellera,2 aDepartment of Molecular Biology and Biophysics, University of Connecticut School of Medicine, Farmington, CT 06030; and bMolecular Biology and Biochemistry Graduate Program, University of Connecticut School of Medicine, Farmington, CT 06030 Edited by Jack D. Griffith, University of North Carolina, Chapel Hill, NC, and approved December 4, 2018 (received for review October 13, 2018) Most DNA viruses that use recombination-dependent mechanisms culating in patient populations (18–22). Additionally, it has long to replicate their DNA encode a single-strand annealing protein been recognized that viral replication intermediates are com- (SSAP). The herpes simplex virus (HSV) single-strand DNA binding posed of complex X- and Y-branched structures as evidenced by protein (SSB), ICP8, is the central player in all stages of DNA electron microscopy (10, 16) and pulsed-field gel electrophoresis replication. ICP8 is a classical replicative SSB and interacts physi- (15, 23, 24). ′ ′ cally and/or functionally with the other viral replication proteins. The HSV exo/SSAP, composed of a 5 -to-3 exonuclease Additionally, ICP8 can promote efficient annealing of complemen- (UL12) and an SSAP (ICP8), is capable of promoting strand ex- tary ssDNA and is thus considered to be a member of the SSAP change in vitro (25, 26). More recently, we have shown that HSV infection stimulates single-strand annealing (27), and ICP8 has family. The role of annealing during HSV infection has been been reported to promote recombineering in transfected cells difficult to assess in part, because it has not been possible to (28).
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