Effective treatment of experimental cytomegalovirus-induced encephalo-meningitis in immunocompromised rats with HPMPC

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 experi...

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Bibliographic Details
Published in:	Antiviral research Vol. 35; no. 2; pp. 105 - 112
Main Authors:	Kloover, J.S., Vanagt, W.Y.R., Stals, F.S., Bruggeman, C.A.
Format:	Journal Article
Language:	English
Published:	Amsterdam Elsevier B.V 01-07-1997 Elsevier
Subjects:	Acquired immunodeficiency syndrome AIDS/HIV Animals Antibiotics. Antiinfectious agents. Antiparasitic agents Antiviral agents Antiviral Agents - therapeutic use Biological and medical sciences Brain - pathology Cytomegalovirus Cytomegalovirus Infections - drug therapy Cytosine - analogs & derivatives Cytosine - therapeutic use Disease Models, Animal Drug Therapy, Combination Encephalomeningitis Ganciclovir - therapeutic use HPMPC Human cytomegalovirus Immune Sera Immunocompromised Host Male Medical sciences Meninges - pathology Meningitis, Viral - drug therapy Organophosphonates Organophosphorus Compounds - therapeutic use Pharmacology. Drug treatments Rats Rats, Inbred BN Time Factors Cytomegalovirus Encephalomeningitis HPMPC Acquired immunodeficiency syndrome Rat Betaherpesvirinae Antiviral Complication Meningitis Immunopathology Nervous system diseases Acyclic nucleotide Herpesviridae Rodentia AIDS Cidofovir Immune deficiency Infection Virus Vertebrata Chemotherapy Experimental disease Mammalia Treatment Viral disease Animal Central nervous system disease Pyrimidine nucleotide
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Summary:	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.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0166-3542 1872-9096
DOI:	10.1016/S0166-3542(97)00019-3