PMID- 15507126 OWN - NLM STAT- MEDLINE DCOM- 20061226 LR - 20181113 IS - 1743-422X (Electronic) IS - 1743-422X (Linking) VI - 1 DP - 2004 Sep 23 TI - Persistent expression of chemokine and chemokine receptor RNAs at primary and latent sites of herpes simplex virus 1 infection. PG - 5 AB - Inflammatory cytokines and infiltrating T cells are readily detected in herpes simplex virus (HSV) infected mouse cornea and trigeminal ganglia (TG) during the acute phase of infection, and certain cytokines continue to be expressed at lower levels in infected TG during the subsequent latent phase. Recent results have shown that HSV infection activates Toll-like receptor signaling. Thus, we hypothesized that chemokines may be broadly expressed at both primary sites and latent sites of HSV infection for prolonged periods of time. Real-time reverse transcriptase-polymrease chain reaction (RT-PCR) to quantify expression levels of transcripts encoding chemokines and their receptors in cornea and TG following corneal infection. RNAs encoding the inflammatory-type chemokine receptors CCR1, CCR2, CCR5, and CXCR3, which are highly expressed on activated T cells, macrophages and most immature dendritic cells (DC), and the more broadly expressed CCR7, were highly expressed and strongly induced in infected cornea and TG at 3 and 10 days postinfection (dpi). Elevated levels of these RNAs persisted in both cornea and TG during the latent phase at 30 dpi. RNAs for the broadly expressed CXCR4 receptor was induced at 30 dpi but less so at 3 and 10 dpi in both cornea and TG. Transcripts for CCR3 and CCR6, receptors that are not highly expressed on activated T cells or macrophages, also appeared to be induced during acute and latent phases; however, their very low expression levels were near the limit of our detection. RNAs encoding the CCR1 and CCR5 chemokine ligands MIP-1alpha, MIP-1beta and RANTES, and the CCR2 ligand MCP-1 were also strongly induced and persisted in cornea and TG during the latent phase. These and other recent results argue that HSV antigens or DNA can stimulate expression of chemokines, perhaps through activation of Toll-like receptors, for long periods of time at both primary and latent sites of HSV infection. These chemokines recruit activated T cells and other immune cells, including DC, that express chemokine receptors to primary and secondary sites of infection. Prolonged activation of chemokine expression could provide mechanistic explanations for certain aspects of HSV biology and pathogenesis. FAU - Cook, W James AU - Cook WJ AD - Millennium Pharmaceuticals Inc., Cambridge, MA 02139, USA. JCook@glycofi.com FAU - Kramer, Martha F AU - Kramer MF FAU - Walker, Russell M AU - Walker RM FAU - Burwell, Timothy J AU - Burwell TJ FAU - Holman, Holly A AU - Holman HA FAU - Coen, Donald M AU - Coen DM FAU - Knipe, David M AU - Knipe DM LA - eng GR - P01 NS035138/NS/NINDS NIH HHS/United States GR - P01 NS35138/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20040923 PL - England TA - Virol J JT - Virology journal JID - 101231645 RN - 0 (Chemokines) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Chemokine) SB - IM MH - Animals MH - Chemokines/*genetics MH - Cornea/metabolism MH - Ganglia/metabolism MH - *Gene Expression Regulation MH - Herpes Simplex/*genetics/*virology MH - Herpesvirus 1, Human/*physiology MH - Leukocytes/metabolism MH - Mice MH - Mice, Inbred ICR MH - RNA, Messenger/genetics/metabolism MH - Receptors, Chemokine/*genetics MH - *Virus Latency PMC - PMC524517 EDAT- 2004/10/28 09:00 MHDA- 2006/12/27 09:00 PMCR- 2004/09/23 CRDT- 2004/10/28 09:00 PHST- 2004/05/25 00:00 [received] PHST- 2004/05/28 00:00 [accepted] PHST- 2004/10/28 09:00 [pubmed] PHST- 2006/12/27 09:00 [medline] PHST- 2004/10/28 09:00 [entrez] PHST- 2004/09/23 00:00 [pmc-release] AID - 1743-422X-1-5 [pii] AID - 10.1186/1743-422X-1-5 [doi] PST - epublish SO - Virol J. 2004 Sep 23;1:5. doi: 10.1186/1743-422X-1-5.