Table 2.
Summary of notable studies and their evidence for or against the Married and Separate Models
| Reference | Viral strain and infection timepoint | Neuronal culture | Assay type and axon location | Findings/model supported |
|---|---|---|---|---|
| Taylor et al., 2012 [20] | PRV 8–10hpi | Rat SCG dissociated cultures | Live cell imaging; proximal and distal axon regions | 96% colocalization of capsid/membrane protein signals during anterograde transport events→Married Model |
| Ibiricu et al., 2011 [60] | HSV-1 F, KOS 16hpi | Rat hippocampal dissociated cultures | Cryo-electron tomography; mid-axon(?) | Predominantly naked capsids (67 of 73 total axonal structures); secondary envelopment events at axon termini, no quantitation→Separate Model |
| Wisner et al., 2011 [25] | HSV-1 YK304; 19–23hpi | Rat DRG in microfluidic chambers, SK-N-SH (induced neuron-like human cells) dissociated cultures | Live cell imaging; undescribed region of axon | Variable colocalization (~50% max) of capsid/glycoprotein signals during anterograde transport events→Married and Separate Models |
| Huang et al., 2011 [22] | PRV, HSV-1 NS, HSV-2 2.12 24, 48 hpi | Rat SCG Campenot Chambered Cultures | TEM; distal axon contained within Campenot chamber | Enveloped capsids in axons across all three viral strains; no quantitation→Married Model |
| Antinone et al., 2010 [24] | HSV-1 18–24hpi | Chick and Rat DRG, mouse Cath.A-differentiated (induced neuron-like cells) dissociated cultures | Live cell imaging; proximal and distal axon | 65%–70% colocalization of capsid/glycoprotein signals during clear anterograde transport events→Married Model |
| Negatsch et al., 2010 [34] | HSV-1 HFEM, SC16, 17+16–24hpi | Rat SCG dissociated cultures | TEM; proximal and distal axon | 75% enveloped virions in axons→Married Model |
| Maresch et al., 2010 [23] | PRV 18hpi | Rat SCG dissociated cultures | TEM; proximal and distal axon | <10% naked capsids in axons→Married Model |
| Miranda-Saksena et al., 2009 [64] | HSV-1 CW1 28hpi | Human DRG explant | TIEM; undefined region of axon | Colocalization of Vp16 and Vp22 on large dense-core vesicles, no colocalization with gB→Separate Model |
| Snyder et al., 2008 [39] | HSV-1 F 18hpi | SK-N-SH dissociated cultures | IF; proximal and distal axon | No detection of glycoproteins (gD/gB) or capsids in axons in Us9-null background; colocalization of Us9, but not gE/gI with capsids in axons→Separate Model |
| Lyman et al., 2007 [15] | PRV 24hpi | Rat SCG explant cultures; dual chamber | Live cell imaging; proximal and distal axon | No viral structural components (tegument, capsid, or glycoprotein) detected in axon in Us9-null background→Married Model |
| Feierbach et al., 2007 [21] | PRV 20hpi | Rat SCG, dual chamber culture | TEM; mid-axon | Mostly enveloped virions in axons, no quantitation→Married Model |
| Miranda-Saksena et al., 2006 [62] | HSV-1 CW1 24 and 48 hpi | Human DRG explant cultures | TEM; varicosities and growth cones | Enveloped and unenveloped capsids at sites of egress; 6 partially enveloped; 1974 “axon processes and regions” examined total→Separate Model |
| Snyder et al., 2006 [38] | HSV-1 F 15–18hpi | SK-N-SH dissociated cultures | IF; proximal and distal axon | Only 3%–6% colocalization of capsid (anti-Vp5) and glycoprotein (anti-gD, gB, gE/gI) signals→Separate Model |
| Antinone et al., 2006 [19] | PRV 10-13hpi | Chick DRG dissociated cultures | Live cell imaging; proximal and distal axon | 85% colocalization of capsid/glycoprotein signals→Married Model |
| Ch'ng and Enquist, 2005 [14] | PRV 14hpi | Rat SCG Campenot Chamber Cultures | TEM; mid-axon | Mostly enveloped virions in axons, no quantitation→Married Model |
| Del Rio et al., 2005 [52] | PRV 12hpi | Rat SCG dissociated cultures | TEM; proximal and distal axon | Mostly enveloped virions in axons, no quantitation→Married Model |
| Tomishima and Enquist, 2001 [13] | PRV 12, 16hpi | Rat SCG dissociated cultures | IF, proximal and distal axon | Capsids and tegument (Vp22, UL25) can be detected in axons despite nonfunctional Us9→Separate Model |
| Miranda-Saksena et al., 2000 [51] | HSV-1 CS1 17 and 24 hpi | Human and Rat DRG dissociated cultures; Brefeldin pretreatment | TEM, TIEM; proximal axon | No glycoproteins (gC) or tegument (Vp16) detected in axons following Brefeldin-A treatment; unenveloped capsids present in axon; no quantitation→Separate Model |
| Ohara et al., 2000 [33] | HSV-1 F 3dpi | Murine trigeminal ganglia axons, in vivo | TIEM; undefined axonal region | Mature virions in vesicles in axons visualized by day 3 of infection→Married Model |
| Holland et al., 1999 [59] | HSV-1 CW1 24hpi | Human DRG, dual chamber cultures | TEM, TIEM; undefined axonal region | Only unenveloped capsids detected, no quantitation; 95% colocalization of Vp5 with Vp16 signal; dense-core vesicles resembling naked capsids detected in uninfected axons→Separate Model |
| LaVail et al., 1997 [32] | HSV-1 H129 3dpi | Murine trigeminal ganglia axons, in vivo | TEM; undefined axonal region | Enveloped virions detected in axonal profiles; no quantitation→Married Model |
| Penfold et al., 1994 [35] | HSV-1 WM1 and WM2 16, 24, 48 hpi | Human DRG explant cultures; dual chamber | TEM; undefined axonal region | Only unenveloped capsids detected in axons (>200), enveloped capsids in soma (20)→Separate Model |
| Lycke et al., 1988 [31] | HSV-1 McIntyre 20hpi | Human DRG dissociated cultures | TEM; undefined axonal region | Enveloped virions detected in axonal profiles; exocytosis of virion transport vesicles; no quantitation→Married Model |
| Kristensson et al., 1974 [29] | HSV-2 G 3dpi | Rabbit retinal ganglia and right superior colliculus | TEM; undefined axonal region | Predominantly enveloped virions detected in axonal processes; no quantitation—> Married Model |
| Cook and Stevens, 1973 [28] | HSV-1 McIntrye 4dpi | Murine DRG, in vivo | TEM; undefined axonal region | Enveloped virions detected in axonal profiles; no quantitation→Married Model |
| Yamamoto et al., 1973 [30] | HSV-1 HF 1–4dpi | Murine coeliac ganglia, in vivo | TEM; undefined axonal region | Enveloped virions detected in groups in axonal profiles; no quantitation→Married Model |
| Hill et al., 1972 [26] | HSV-1, –2 6–7dpi | Murine sciatic nerve ganglia | TEM; undefined axonal region | Enveloped virions detected in axonal endoplasmic reticulum; no quantitation→Married Model |
Key points relating to viral strain, cell type, and location are noted. The key findings have been summarized as well as whether the interpretation supports the Married or Separate models. The studies have been organized by date published, most recent first.
SCG, superior cervical ganglia; DRG, dorsal root ganglia; TEM, transmission electron microscopy; TIEM, transmission immuno-electron microscopy;IF, immuno-fluorescence.