PMID- 18055810 OWN - NLM STAT- MEDLINE DCOM- 20080129 LR - 20220208 IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 48 IP - 12 DP - 2007 Dec TI - Macrophages are important determinants of acute ocular HSV-1 infection in immunized mice. PG - 5605-15 AB - PURPOSE: 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. FAU - Mott, Kevin AU - Mott K AD - Center for Neurobiology and Vaccine Development, Ophthalmology Research Laboratories, Cedars-Sinai Medical Center Burns and Allen Research Institute, Los Angeles, California 90048, USA. FAU - Brick, David J AU - Brick DJ FAU - van Rooijen, Nico AU - van Rooijen N FAU - Ghiasi, Homayon AU - Ghiasi H LA - eng GR - R01 EY014966/EY/NEI NIH HHS/United States GR - EY14966/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Antibodies, Viral) RN - 0 (Cytokines) RN - 0 (Herpes Simplex Virus Vaccines) RN - 0 (Vaccines, DNA) RN - 0 (Viral Envelope Proteins) RN - 3OWL53L36A (Mannitol) RN - 9007-81-2 (Freund's Adjuvant) SB - IM MH - Acute Disease MH - Animals MH - Antibodies, Viral/blood MH - Blepharitis/prevention & control/virology MH - Cytokines/metabolism MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Freund's Adjuvant/therapeutic use MH - Herpes Simplex Virus Vaccines/*therapeutic use MH - Herpesvirus 1, Human/*physiology MH - Keratitis, Dendritic/mortality/*prevention & control/virology MH - Macrophages/*physiology MH - Mannitol/analogs & derivatives/therapeutic use MH - Mice MH - Mice, Inbred BALB C MH - Vaccination MH - Vaccines, DNA/*therapeutic use MH - Viral Envelope Proteins/genetics/immunology MH - Virus Latency MH - Virus Replication/physiology EDAT- 2007/12/07 09:00 MHDA- 2008/01/30 09:00 CRDT- 2007/12/07 09:00 PHST- 2007/12/07 09:00 [pubmed] PHST- 2008/01/30 09:00 [medline] PHST- 2007/12/07 09:00 [entrez] AID - 48/12/5605 [pii] AID - 10.1167/iovs.07-0894 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5605-15. doi: 10.1167/iovs.07-0894.