Axonal transport and sorting of herpes simplex virus components in a mature mouse visual system.
The time course for delivery and transport of two major proteins of herpes simplex virus (HSV) has been determined for mature mouse retinal ganglion cell axons in vivo. Twenty-four hours after intravitreal injection of HSV, valacyclovir was introduced into the drinking water of the mice to inhibit subsequent viral replication. Without treatment, viral spread and replication in periaxonal glial cells confound study of axonal transport. At 2 to 5 days after infection, the animals were sacrificed and contiguous segments of the optic pathway were removed. Immunofluorescence microscopy indicated that the number of infected astrocytes was reduced in the proximal optic nerve and eliminated in the optic tract. Western blots of the retina with antibodies for envelope and capsid components, glycoprotein D (gD) and VP5, respectively, revealed that both components were expressed in retinal homogenates by 2 days. Results of reverse transcription-PCR indicated that there was no gD mRNA present in the treated optic tract 5 days after infection. Therefore, we conclude that gD is transcribed from viral mRNA in the retinal ganglion cell bodies. The gD accumulated in the proximal ganglion cell axon by 2 days and reached the most distal segment after 3 days. The VP5 first appeared in the proximal axons at 4 days, about 48 h after the appearance of gD. Thus, gD entered the axon earlier and independent of VP5. These finding confirm the subassembly model of viral transport in neurons and suggest that there is a 4- to 5-day window for initiation of effective antiviral treatment with valacyclovir.
LaVail
Jennifer H
JH
Department of Anatomy, University of California- San Francisco, 94143, USA. jhl@itsa.ucsf.edu
Tauscher
Andrew N
AN
Aghaian
Elda
E
Harrabi
Ons
O
Sidhu
Sukhvinder S
SS
D000212:Acyclovir / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001253:Astrocytes / Q000821:virology; D001370:Axonal Transport / Q000502:physiology*; D036022:Capsid Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D016849:Keratitis, Herpetic / Q000188:drug therapy / Q000821:virology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009900:Optic Nerve / Q000166:cytology / Q000821:virology; D012160:Retina / Q000166:cytology / Q000821:virology; D012165:Retinal Ganglion Cells / Q000821:virology*; D018139:Simplexvirus / Q000187:drug effects / Q000472:pathogenicity* / Q000502:physiology*; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014759:Viral Envelope Proteins / Q000378:metabolism; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; D036022:Capsid Proteins; C442523:VP5 protein, Herpes simplex virus type 1; D014759:Viral Envelope Proteins; C039447:glycoprotein D, Human herpesvirus 1; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir