The Herpes Simplex Virus Type 1 (HSV-1) Glycoprotein K(gK) is Essential for Viral Corneal Spread and Neuroinvasiveness

Author: David Andrew   Baghian A.   Foster T. P.   Chouljenko V. N.   Kousoulas K. G.  

Publisher: Informa Healthcare

ISSN: 0271-3683

Source: Current Eye Research, Vol.33, Iss.5-6, 2008-05, pp. : 455-467

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Abstract

Purpose: To determine the role of herpes simplex virus-1 (HSV-1) glycoprotein K(gK) in corneal infection, neuroinvasion, and virus latency in trigeminal ganglia of mice. Methods: The recombinant virus HSV-1 (McKrae) ∆ gK (MK∆ gK) carrying a deletion of the gK gene was constructed by insertional/deletion mutagenesis and replaced by a gene cassette constitutively expressing the enhanced green fluorescence protein. The gK deletion of the MK∆ gK virus was rescued to produce the wild-type-like virus MKgK. Balb/c mice were infected ocularly with either virus, and the infection pattern in the eye, clinical disease progression, and establishment of viral latency was monitored. Results: Mice infected with the MK∆ gK strain produced in a gK complementing cell line did not exhibit clinical signs when compared with mice infected with the MKgK virus. Direct visualization of infected eyes revealed that the MK∆ gK virus was unable to spread in mouse corneas, while the MKgK rescued virus spread efficiently. Nineteen of 20 scarified and 5/12 unscarified mice infected with the MKgK virus produced infectious virus after coculture with permissive cells, while 0/20 scarified and 0/12 unscarified mice infected with the MK∆ gK virus produced infectious virus. HSV DNA was detected in trigeminal ganglia by PCR in 19/20 scarified and 9/12 unscarified mice inoculated with MKgK, while HSV DNA was detected in the trigeminal ganglia of 3/20 scarified and 0/12 unscarified mice inoculated with MK∆ gK. Conclusions: The results show that HSV-1 gK is essential for efficient replication and spread in the corneal epithelium and trigeminal ganglia neuroinvasion in MK∆ gK inoculated mice.