title: Effective treatment of experimental cytomegalovirus-induced encephalo-meningitis in immunocompromised rats with HPMPC.
abstract: Cytomegalovirus (CMV)-induced encephalomeningitis is a dramatic complication in patients with the acquired immunodeficiency syndrome (AIDS) and treatment of this infection remains a major clinical problem. In order to study the pathogenesis and treatment of CMV-induced encephalomeningitis, we experimentally induced intracranial rat CMV (RCMV) infection in rats that were immunosuppressed by total body X-irradiation. CMV infection was monitored by viral plaque assay for estimation of the viral load. CMV-induced pathology, the presence of CMV-infected cells, as well as the presence of T-lymphocytes and monocytes/macrophages were studied by histopathologic and immunohistochemical staining techniques. The meninges showed CMV infection in mononuclear infiltrative cells and in endothelium of small blood vessels 8 days after intracerebral inoculation. This was accompagnied by multiple haemorraghes and inflammatory cell infiltration. The infection and inflammatory response persisted for at least 21 days p.i. Animals were treated with (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMPC), 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), hyperimmune serum (HIS) and both DHPG and HIS combined. Treatment with one dosage of HPMPC at 20 mg/kg effectively reduced virus titers. However, all other treatment modalities were not effective. In conclusion, the pathology of RCMV-induced encephalomeningitis in immunocompromised rats closely resembles that of AIDS patients. The infection is effectively treated by HPMPC.
authors.affiliation: Department of Medical Microbiology, University of Maastricht, The Netherlands.
authors.forename: J S
authors.initials: JS
authors.lastname: Kloover
authors.forename: W Y
authors.initials: WY
authors.lastname: Vanagt
authors.forename: F S
authors.initials: FS
authors.lastname: Stals
authors.forename: C A
authors.initials: CA
authors.lastname: Bruggeman
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000627:therapeutic use*; D001921:Brain / Q000473:pathology; D000077404:Cidofovir; D003586:Cytomegalovirus Infections / Q000188:drug therapy*; D003596:Cytosine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D015774:Ganciclovir / Q000627:therapeutic use; D007106:Immune Sera; D016867:Immunocompromised Host; D008297:Male; D008578:Meninges / Q000473:pathology; D008587:Meningitis, Viral / Q000188:drug therapy*; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000627:therapeutic use*; D051381:Rats; D011914:Rats, Inbred BN; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D007106:Immune Sera; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D003596:Cytosine; D000077404:Cidofovir; D015774:Ganciclovir