PMID- 32937797 OWN - NLM STAT- MEDLINE DCOM- 20210302 LR - 20210302 IS - 1999-4915 (Electronic) IS - 1999-4915 (Linking) VI - 12 IP - 9 DP - 2020 Sep 14 TI - Two Separate Tyrosine-Based YXXL/Phi Motifs within the Glycoprotein E Cytoplasmic Tail of Bovine Herpesvirus 1 Contribute in Virus Anterograde Neuronal Transport. LID - 10.3390/v12091025 [doi] LID - 1025 AB - Bovine herpesvirus 1 (BHV-1) causes respiratory infection and abortion in cattle. Following a primary infection, BHV-1 establishes lifelong latency in the trigeminal ganglia (TG). Periodic reactivation of the latent virus in TG neurons results in anterograde virus transport to nerve endings in the nasal mucosa and nasal virus shedding. The BHV-1 glycoprotein E cytoplasmic tail (gE-CT) is necessary for virus cell-to-cell spread in epithelial cells and neuronal anterograde transport. Recently, we identified two tyrosine residues, Y467 and Y563, within the tyrosine-based motifs (467)YTSL(470) and (563)YTVV(566), which, together, account for the gE CT-mediated efficient cell-to-cell spread of BHV-1 in epithelial cells. Here, we determined that in primary neuron cultures in vitro, the individual alanine exchange Y467A or Y563A mutants had significantly diminished anterograde axonal spread. Remarkably, the double-alanine-exchanged Y467A/Y563A mutant virus was not transported anterogradely. Following intranasal infection of rabbits, both wild-type (wt) and the Y467A/Y563A mutant viruses established latency in the TG. Upon dexamethasone-induced reactivation, both wt and the mutant viruses reactivated and replicated equally efficiently in the TG. However, upon reactivation, only the wt, not the mutant, was isolated from nasal swabs. Therefore, the gE-CT tyrosine residues Y467 and Y563 together are required for gE CT-mediated anterograde neuronal transport. FAU - Yezid, Hocine AU - Yezid H AD - Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. FAU - Lay, Christian T AU - Lay CT AD - Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. FAU - Pannhorst, Katrin AU - Pannhorst K AD - Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. FAU - Chowdhury, Shafiqul I AU - Chowdhury SI AUID- ORCID: 0000-0002-8008-5512 AD - Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA. LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200914 PL - Switzerland TA - Viruses JT - Viruses JID - 101509722 RN - 0 (Glycoproteins) RN - 0 (Viral Envelope Proteins) RN - 42HK56048U (Tyrosine) SB - IM MH - Animals MH - Biological Transport/*physiology MH - Cattle MH - Cattle Diseases/virology MH - Cell Line MH - Glycoproteins/*metabolism MH - Herpesviridae Infections/virology MH - Herpesvirus 1, Bovine/genetics/*physiology MH - Lab-On-A-Chip Devices MH - Neurons/*virology MH - Rabbits MH - Trigeminal Ganglion/virology MH - Tyrosine/*metabolism MH - Viral Envelope Proteins/genetics/metabolism MH - Virus Activation MH - Virus Latency MH - Virus Shedding PMC - PMC7551581 OTO - NOTNLM OT - BHV-1 OT - YXXL/Phi sorting motifs OT - anterograde neuronal traffic OT - compartmentalized primary neurons OT - gE CT domain OT - glycoprotein E OT - microfluidic chambers OT - reactivation from latency COIS- The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results. EDAT- 2020/09/18 06:00 MHDA- 2021/03/03 06:00 PMCR- 2020/09/01 CRDT- 2020/09/17 01:02 PHST- 2020/07/12 00:00 [received] PHST- 2020/08/31 00:00 [revised] PHST- 2020/09/12 00:00 [accepted] PHST- 2020/09/17 01:02 [entrez] PHST- 2020/09/18 06:00 [pubmed] PHST- 2021/03/03 06:00 [medline] PHST- 2020/09/01 00:00 [pmc-release] AID - v12091025 [pii] AID - viruses-12-01025 [pii] AID - 10.3390/v12091025 [doi] PST - epublish SO - Viruses. 2020 Sep 14;12(9):1025. doi: 10.3390/v12091025.