PMID- 29187538 OWN - NLM STAT- MEDLINE DCOM- 20180419 LR - 20190705 IS - 1098-5514 (Electronic) IS - 0022-538X (Print) IS - 0022-538X (Linking) VI - 92 IP - 4 DP - 2018 Feb 15 TI - The Absence of DHHC3 Affects Primary and Latent Herpes Simplex Virus 1 Infection. LID - 10.1128/JVI.01599-17 [doi] LID - e01599-17 AB - UL20, an essential herpes simplex virus 1 (HSV-1) protein, is involved in cytoplasmic envelopment of virions and virus egress. We reported recently that UL20 can bind to a host protein encoded by the zinc finger DHHC-type containing 3 (ZDHHC3) gene (also known as Golgi-specific DHHC zinc finger protein [GODZ]). Here, we show for the first time that HSV-1 replication is compromised in murine embryonic fibroblasts (MEFs) isolated from GODZ(-/-) mice. The absence of GODZ resulted in blocking palmitoylation of UL20 and altered localization and expression of UL20 and glycoprotein K (gK); the expression of gB and gC; and the localization and expression of tegument and capsid proteins within HSV-1-infected MEFs. Electron microscopy revealed that the absence of GODZ limited the maturation of virions at multiple steps and affected the localization of virus and endoplasmic reticulum morphology. Virus replication in the eyes of ocularly HSV-1-infected GODZ(-/-) mice was significantly lower than in HSV-1-infected wild-type (WT) mice. The levels of UL20, gK, and gB transcripts in the corneas of HSV-1-infected GODZ(-/-) mice on day 5 postinfection were markedly lower than in WT mice, whereas only UL20 transcripts were reduced in trigeminal ganglia (TG). In addition, HSV-1-infected GODZ(-/-) mice showed notably lower levels of corneal scarring, and HSV-1 latency reactivation was also reduced. Thus, normal HSV-1 infectivity and viral pathogenesis are critically dependent on GODZ-mediated palmitoylation of viral UL20.IMPORTANCE HSV-1 infection is widespread. Ocular infection can cause corneal blindness; however, approximately 70 to 90% of American adults exposed to the virus show no clinical symptoms. In this study, we show for the first time that the absence of a zinc finger protein called GODZ affects primary and latent infection, as well as reactivation, in ocularly infected mice. The reduced virus infectivity is due to the absence of the GODZ interaction with HSV-1 UL20. These results strongly suggest that binding of UL20 to GODZ promotes virus infectivity in vitro and viral pathogenesis in vivo. CI - Copyright (c) 2018 American Society for Microbiology. FAU - Wang, Shaohui AU - Wang S AD - Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Los Angeles, California, USA. FAU - Mott, Kevin R AU - Mott KR AD - Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Los Angeles, California, USA. FAU - Cilluffo, Marianne AU - Cilluffo M AD - Brain Research Institute, UCLA, Los Angeles, California, USA. FAU - Kilpatrick, Casey L AU - Kilpatrick CL AD - Department of Biology, Biochemistry and Molecular Biology, and Psychiatry, Pennsylvania State University, University Park, Pennsylvania, USA. FAU - Murakami, Shoko AU - Murakami S AD - Department of Biology, Biochemistry and Molecular Biology, and Psychiatry, Pennsylvania State University, University Park, Pennsylvania, USA. FAU - Ljubimov, Alexander V AU - Ljubimov AV AD - Eye Program, Board of Governors Regenerative Medicine Institute, Cedars-Sinai Medical Center, and David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. FAU - Kousoulas, Konstantin G AU - Kousoulas KG AD - Division of Biotechnology and Molecular Medicine, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana, USA. FAU - Awasthi, Sita AU - Awasthi S AD - Infectious Disease Division, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA. FAU - Luscher, Bernhard AU - Luscher B AD - Department of Biology, Biochemistry and Molecular Biology, and Psychiatry, Pennsylvania State University, University Park, Pennsylvania, USA. FAU - Ghiasi, Homayon AU - Ghiasi H AD - Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Los Angeles, California, USA ghiasih@cshs.org. LA - eng GR - R01 EY013615/EY/NEI NIH HHS/United States GR - R01 MH060989/MH/NIMH NIH HHS/United States GR - R01 MH062391/MH/NIMH NIH HHS/United States GR - R01 MH099851/MH/NIMH NIH HHS/United States PT - Journal Article DEP - 20180130 PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (GODZ protein, mouse) RN - 0 (Membrane Proteins) RN - 0 (UL20 protein, Herpes simplex virus type 1) RN - 0 (Viral Proteins) SB - IM MH - Animals MH - Cell Line MH - Cornea/virology MH - Cytoplasm/virology MH - Female MH - Herpes Simplex/*virology MH - Herpesvirus 1, Human/genetics/*physiology MH - Lipoylation MH - Male MH - Membrane Proteins/genetics/*metabolism MH - Mice MH - Mice, Inbred C57BL MH - Mice, Knockout MH - Microscopy, Electron MH - Trigeminal Ganglion/virology MH - Viral Proteins/genetics/*metabolism MH - *Virus Latency MH - *Virus Replication PMC - PMC5790959 OTO - NOTNLM OT - EM OT - GODZ OT - HSV-1 OT - TG OT - knockout OT - latency OT - latency reactivation OT - primary infection OT - zinc finger protein EDAT- 2017/12/01 06:00 MHDA- 2018/04/20 06:00 PMCR- 2018/07/30 CRDT- 2017/12/01 06:00 PHST- 2017/09/08 00:00 [received] PHST- 2017/11/15 00:00 [accepted] PHST- 2017/12/01 06:00 [pubmed] PHST- 2018/04/20 06:00 [medline] PHST- 2017/12/01 06:00 [entrez] PHST- 2018/07/30 00:00 [pmc-release] AID - JVI.01599-17 [pii] AID - 01599-17 [pii] AID - 10.1128/JVI.01599-17 [doi] PST - epublish SO - J Virol. 2018 Jan 30;92(4):e01599-17. doi: 10.1128/JVI.01599-17. Print 2018 Feb 15.