scholarly journals Squid Axoplasm Supports the Retrograde Axonal Transport of Herpes Simplex Virus

1999 ◽  
Vol 197 (2) ◽  
pp. 257-258 ◽  
Author(s):  
E. L. Bearer ◽  
M. L. Schlief ◽  
X. O. Breakefield ◽  
D. E. Schuback ◽  
T. S. Reese ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Axonal Transport ◽  
Retrograde Axonal Transport ◽  
Simplex Virus

scholarly journals The herpes simplex virus type I deamidase enhances propagation but is dispensable for retrograde axonal transport into the nervous system

2019 ◽  
Author(s):  
Austin M. Stults ◽  
Gregory A. Smith
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Axonal Transport ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Retrograde Axonal Transport ◽  
Nerve Endings ◽  
Type I ◽  
Simplex Virus

ABSTRACTUpon replication in mucosal epithelia and transmission to nerve endings, capsids of herpes simplex virus type I (HSV-1) travel retrograde within axons to peripheral ganglia where life-long latent infections are established. A capsid-bound tegument protein, pUL37, is an essential effector of retrograde axonal transport and also houses a deamidase activity that antagonizes innate immune signaling. In this report, we examined whether the deamidase of HSV-1 pUL37 contributes to the neuroinvasive retrograde axonal transport mechanism. We conclude that neuroinvasion is enhanced by the deamidase, but the critical contribution of pUL37 to retrograde axonal transport functions independently of this activity.IMPORTANCEHerpes simplex virus type 1 invades the nervous system by entering nerve endings and sustaining long-distance retrograde axonal transport to reach neuronal nuclei in ganglia of the peripheral nervous system. The incoming viral particle carries a deamidase activity on its surface that antagonizes antiviral responses. We examined the contribution of the deamidase to the hallmark neuroinvasive property of this virus.

scholarly journals The Herpes Simplex Virus 1 Deamidase Enhances Propagation but Is Dispensable for Retrograde Axonal Transport into the Nervous System

2019 ◽  
Vol 93 (22) ◽  
Author(s):  
Austin M. Stults ◽  
Gregory A. Smith
Keyword(s):  
Nervous System ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Axonal Transport ◽  
Retrograde Axonal Transport ◽  
Nerve Endings ◽  
Long Distance ◽  
Herpes Simplex Virus 1 ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Upon replication in mucosal epithelia and transmission to nerve endings, capsids of herpes simplex virus 1 (HSV-1) travel retrogradely within axons to peripheral ganglia, where life-long latent infections are established. A capsid-bound tegument protein, pUL37, is an essential effector of retrograde axonal transport and also houses a deamidase activity that antagonizes innate immune signaling. In this report, we examined whether the deamidase of HSV-1 pUL37 contributes to the neuroinvasive retrograde axonal transport mechanism. We conclude that neuroinvasion is enhanced by the deamidase, but the critical contribution of pUL37 to retrograde axonal transport functions independently of this activity. IMPORTANCE Herpes simplex virus 1 invades the nervous system by entering nerve endings and sustaining long-distance retrograde axonal transport to reach neuronal nuclei in ganglia of the peripheral nervous system. The incoming viral particle carries a deamidase activity on its surface that antagonizes antiviral responses. We examined the contribution of the deamidase to the hallmark neuroinvasive property of this virus.

scholarly journals Herpes Simplex Virus Utilizes the Large Secretory Vesicle Pathway for Anterograde Transport of Tegument and Envelope Proteins and for Viral Exocytosis from Growth Cones of Human Fetal Axons

2009 ◽  
Vol 83 (7) ◽  
pp. 3187-3199 ◽  
Author(s):  
Monica Miranda-Saksena ◽  
Ross A. Boadle ◽  
Anupriya Aggarwal ◽  
Bibing Tijono ◽  
Frazer J. Rixon ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Axonal Transport ◽  
Virus Assembly ◽  
Growth Cones ◽  
Secretory Vesicle ◽  
Envelope Proteins ◽  
Anterograde Axonal Transport ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Axonal transport of herpes simplex virus (HSV-1) is essential for viral infection and spread in the peripheral nervous system of the host. Therefore, the virus probably utilizes existing active transport and targeting mechanisms in neurons for virus assembly and spread from neurons to skin. In the present study, we used transmission immnunoelectron microscopy to investigate the nature and origin of vesicles involved in the anterograde axonal transport of HSV-1 tegument and envelope proteins and of vesicles surrounding partially and fully enveloped capsids in growth cones. This study aimed to elucidate the mechanism of virus assembly and exit from axons of human fetal dorsal root ganglia neurons. We demonstrated that viral tegument and envelope proteins can travel in axons independently of viral capsids and were transported to the axon terminus in two types of transport vesicles, tubulovesicular membrane structures and large dense-cored vesicles. These vesicles and membrane carriers were derived from the trans-Golgi network (TGN) and contained key proteins, such as Rab3A, SNAP-25, GAP-43, and kinesin-1, involved in the secretory and exocytic pathways in axons. These proteins were also observed on fully and partially enveloped capsids in growth cones and on extracellular virions. Our findings provide further evidence to the subassembly model of separate transport in axons of unenveloped capsids from envelope and tegument proteins with final virus assembly occurring at the axon terminus. We postulate that HSV-1 capsids invaginate tegument- and envelope-bearing TGN-derived vesicles and utilize the large secretory vesicle pathway of exocytosis for exit from axons.

scholarly journals Herpes Simplex Virus gE/gI and US9 Promote both Envelopment and Sorting of Virus Particles in the Cytoplasm of Neurons, Two Processes That Precede Anterograde Transport in Axons

2017 ◽  
Vol 91 (11) ◽  
Author(s):  
Grayson DuRaine ◽  
Todd W. Wisner ◽  
Paul Howard ◽  
Melissa Williams ◽  
David C. Johnson
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Membrane Proteins ◽  
Axonal Transport ◽  
Neuronal Cell ◽  
Anterograde Transport ◽  
Peripheral Tissues ◽  
Virus Particles ◽  
Anterograde Axonal Transport ◽  
Simplex Virus

ABSTRACT Herpes simplex virus (HSV) anterograde transport in neuronal axons is vital, allowing spread from latently infected ganglia to epithelial tissues, where viral progeny are produced in numbers allowing spread to other hosts. The HSV membrane proteins gE/gI and US9 initiate the process of anterograde axonal transport, ensuring that virus particles are transported from the cytoplasm into the most proximal segments of axons. These proteins do not appear to be important once HSV is inside axons. We previously described HSV double mutants lacking both gE and US9 that failed to transport virus particles into axons. Here we show that gE− US9− double mutants accumulate large quantities of unenveloped and partially enveloped capsids in neuronal cytoplasm. These defects in envelopment can explain the defects in axonal transport of enveloped virions. In addition, the unenveloped capsids that accumulated were frequently bound to cytoplasmic membranes, apparently immobilized in intermediate stages of envelopment. A gE-null mutant produced enveloped virions, but these accumulated in large numbers in the neuronal cytoplasm rather than reaching cell surfaces as wild-type HSV virions do. Thus, in addition to the defects in envelopment, there was missorting of capsids and enveloped particles in the neuronal cytoplasm, which can explain the reduced anterograde transport of unenveloped capsids and enveloped virions. These mechanisms differ substantially from existing models suggesting that gE/gI and US9 function by tethering HSV particles to kinesin microtubule motors. The defects in assembly of gE− US9− mutant virus particles were novel because they were neuron specific, in keeping with observations that US9 is neuron specific. IMPORTANCE Herpes simplex virus (HSV) and other alphaherpesviruses, such as varicella-zoster virus, depend upon the capacity to navigate in neuronal axons. To do this, virus particles tether themselves to dyneins and kinesins that motor along microtubules from axon tips to neuronal cell bodies (retrograde transport) or from cell bodies to axon tips (anterograde transport). This transit in axons is essential for alphaherpesviruses to establish latency in ganglia and then to reactivate and move back to peripheral tissues for spread to other hosts. Anterograde transport of HSV requires two membrane proteins: gE/gI and US9. Our studies reveal new mechanisms for how gE/gI and US9 initiate anterograde axonal transport. HSV mutants lacking both gE and US9 fail to properly assemble enveloped virus particles in the cytoplasm, which blocks anterograde transport of enveloped particles. In addition, there are defects in the sorting of virus particles such that particles, when formed, do not enter proximal axons.

scholarly journals Axonal Transport and Sorting of Herpes Simplex Virus Components in a Mature Mouse Visual System

2003 ◽  
Vol 77 (11) ◽  
pp. 6117-6126 ◽  
Author(s):  
Jennifer H. LaVail ◽  
Andrew N. Tauscher ◽  
Elda Aghaian ◽  
Ons Harrabi ◽  
Sukhvinder S. Sidhu
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Ganglion Cell ◽  
Axonal Transport ◽  
Retinal Ganglion Cell ◽  
Optic Tract ◽  
Retinal Ganglion ◽  
Viral Spread ◽  
Mature Mouse ◽  
Simplex Virus

ABSTRACT 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.

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