Macrophages are important determinants of acute ocular HSV-1 infection in immunized mice.
OBJECTIVE
To determine the effect of macrophage depletion on herpes simplex virus type (HAV)-1 replication in the eye and on the establishment of latency in trigeminal ganglia (TG) of immunized and ocularly infected mice.


METHODS
BALB/c mice were immunized with five HSV-1 glycoprotein DNA genes or were sham immunized. The virulent HSV-1 strain KOS was used as a positive vaccine control. Immunized mice were depleted of their macrophages by dichloromethylene diphosphonate (Cl(2)MDP) injection. After ocular infection with the HSV-1 strain McKrae, virus replication in the eye, blepharitis, corneal scarring, and dermatitis were determined. Finally, the copy numbers of latency-associated transcript (LAT) and CD4(+) and CD8(+) T-cell transcripts in the TGs of surviving mice 30 days after infection were determined by RT-PCR.


RESULTS
Depletion of macrophages in immunized mice increased HSV-1 replication in the eye of infected mice between days 1 and 5 after ocular infection. Depletion of macrophages did not alter the HSV-1-induced death or corneal scarring in immunized mice. Macrophage depletion, however, resulted in increased blepharitis in immunized mice. Finally, macrophage depletion had no effect on the establishment of latency in immunized mice, as the TGs from both depleted and mock-depleted mice were negative for the presence of the LAT transcript.


CONCLUSIONS
In immunized mice during primary HSV-1 ocular infection, macrophages play an important role in vaccine efficacy against HSV-1 replication in the eye and blepharitis in infected mice. During the latent stage of HSV-1 infection, however, macrophage depletion failed to have any observable effect on HSV-1 latency in the TGs of infected mice.
Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA.
Kevin
K
Mott
David J
DJ
Brick
Nico
N
van Rooijen
Homayon
H
Ghiasi
D000208:Acute Disease; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D001762:Blepharitis / Q000517:prevention & control / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005620:Freund's Adjuvant / Q000627:therapeutic use; D022301:Herpes Simplex Virus Vaccines / Q000627:therapeutic use*; D018259:Herpesvirus 1, Human / Q000502:physiology*; D007635:Keratitis, Dendritic / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D008264:Macrophages / Q000502:physiology*; D008353:Mannitol / Q000031:analogs & derivatives / Q000627:therapeutic use; D051379:Mice; D008807:Mice, Inbred BALB C; D014611:Vaccination; D019444:Vaccines, DNA / Q000627:therapeutic use*; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology; D017735:Virus Latency; D014779:Virus Replication / Q000502:physiology
D000914:Antibodies, Viral; D016207:Cytokines; D022301:Herpes Simplex Virus Vaccines; D019444:Vaccines, DNA; D014759:Viral Envelope Proteins; D008353:Mannitol; D005620:Freund's Adjuvant