Interferon-gamma, macrophages, and virus spread after HSV-1 injection

Invest Ophthalmol Vis Sci. 2011 Jun 7;52(7):3984-93. doi: 10.1167/iovs.10-6449.

Abstract

Purpose: After uniocular anterior chamber (AC) injection of HSV-1, the anterior segment of BALB/c mice becomes inflamed and infected; however, virus does not spread from the anterior segment to cause retinitis in the injected eye. The purpose of these studies was to determine whether interferon (IFN-)-γ and Mac-1(+) cells play a role in preventing direct anterior-to-posterior spread of HSV-1 in the injected eye.

Methods: One AC of adult female BALB/c mice was injected with HSV-1 (KOS). The location of IFN-α, IFN-β, and IFN-γ in the injected eye was determined by immunofluorescence, and mRNA expression was quantified by qPCR. Injected eyes of IFN-γ knockout or clodronate-treated macrophage-depleted mice were examined to determine whether the absence of IFN-γ or Mac-1(+) macrophages affected the sites or timing of virus spread.

Results: IFN-α, IFN-β, and IFN-γ were observed in the anterior segment of injected eyes through 72 hours and mRNA levels of IFN-β and IFN-γ were increased in virus-infected eyes 48 to 120 hours after infection. However, the absence of IFN-γ or macrophages did not affect either the sites or the timing of HSV-1 infection in injected eyes.

Conclusions: Protection of the retina of the injected eye does not depend on a single cell type or cytokine. In addition, in the eye, as in other sites of the body, there are redundancies in the innate response to virus infection.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anterior Chamber / immunology
  • Anterior Chamber / virology
  • Female
  • Herpes Simplex / immunology*
  • Herpes Simplex / virology*
  • Herpesvirus 1, Human / growth & development
  • Herpesvirus 1, Human / immunology*
  • Interferon-alpha / genetics
  • Interferon-alpha / immunology
  • Interferon-alpha / metabolism
  • Interferon-beta / genetics
  • Interferon-beta / immunology
  • Interferon-beta / metabolism
  • Interferon-gamma / genetics
  • Interferon-gamma / immunology
  • Interferon-gamma / metabolism
  • Interferons* / genetics
  • Interferons* / immunology
  • Interferons* / metabolism
  • Macrophage-1 Antigen / metabolism
  • Macrophages / immunology
  • Macrophages / metabolism
  • Macrophages / virology*
  • Mice
  • Mice, Inbred BALB C
  • Polymerase Chain Reaction
  • Posterior Eye Segment / immunology
  • Posterior Eye Segment / virology

Substances

  • Interferon-alpha
  • Macrophage-1 Antigen
  • Interferon-beta
  • Interferon-gamma
  • Interferons