Overexpression of herpes simplex virus glycoprotein K (gK) alters expression of HSV receptors in ocularly-infected mice.

Abstract

PURPOSE:

We have shown previously that HSV-1 glycoprotein K (gK) exacerbates corneal scarring (CS) in mice and rabbits. Here, we investigated the relative impact of gK overexpression on host responses during primary corneal infection and latency in trigeminal ganglia (TG) of infected mice.

METHODS:

Mice were infected ocularly with HSV-gK(3) (expressing two extra copies of gK replacing latency associated transcript [LAT]), HSV-gK(3) revertant (HSV-gK(3)R), or wild-type HSV-1 strain McKrae. Individual corneas on day 5 post infection (PI) and TG on day 28 PI were isolated and used for detection of gB DNA in the TG, HSV-1 receptors in the cornea and TG, and inflammatory infiltrates in TG.

RESULTS:

During primary HSV-1 infection, gK overexpression resulted in altered expression of herpesvirus entry mediator (HVEM), 3-O-sulfated heparin sulfate (3-OS-HS), paired immunoglobulin-like type 2 receptor-α (PILR-α), nectin-1, and nectin-2 in cornea of BALB/c, but not C57BL/6 mice. However, gK overexpression did have an effect on 3-OS-HS, PILR-α, nectin-1, and nectin-2 expression (but not HVEM expression) in TG of C57BL/6 mice during latency. These differences did not affect the level of latency, but instead were correlated with the presence of CS. The presence of LAT increased HVEM expression and this effect was enhanced further by the presence of CS in latently-infected mice. Finally, the presence of LAT, but not overexpression of gK, affected CD4, CD8, TNF-α, Tim-3, PD-1, IL-21, IL-2, and IFN-γ expression in TG.

CONCLUSIONS:

We demonstrate a novel link between gK exacerbation of CS and HSV-1 receptors, suggesting a gK-induced molecular route for the pathogenesis as well as selective advantage of these entry routes for the pathogen during latency-reactivation cycle.

• Authors: Sariah J Allen, Kevin R Mott, Homayon Ghiasi
• Journal: Investigative ophthalmology & visual science (Invest Ophthalmol Vis Sci) Vol. 55 Issue 4 Pg. 2442-51 (Apr 15 2014) ISSN: 1552-5783 [Electronic] United States
• PMID: 24667863 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• RNA, Viral
• Receptors, Virus
• UL53 protein, Human herpesvirus 1
• Viral Proteins
• simplexvirus receptor

Topics

• Animals
• Cells, Cultured
• Cornea (metabolism, pathology, virology)
• Disease Models, Animal
• Female
• Gene Expression Regulation
• Herpesvirus 1, Human (genetics, metabolism)
• Keratitis, Herpetic (genetics, metabolism, virology)
• Mice
• Mice, Inbred BALB C
• Mice, Inbred C57BL
• RNA, Viral (genetics)
• Rabbits
• Real-Time Polymerase Chain Reaction
• Receptors, Virus (biosynthesis, genetics)
• Viral Proteins (biosynthesis, genetics)
• Virus Replication