title: Flow cytometric method for the detection of gpI antigens of varicella zoster virus and evaluation of anti-VZV agents.
abstract: Varicella zoster virus (VZV) is responsible for a primary infection (varicella) and, upon reactivation, zoster, which in immunocompromised patients, may both lead to life-threatening disseminated disease. There is a great need for antiviral compounds that are effective inhibitors of VZV replication and for rapid and accurate methods for evaluating viral sensitivity to candidate anti-VZV drugs. With the monoclonal antibody (mAb) (VL8), which is directed against the gpI of VZV, and using the fluorescence-activated cell sorter (FACS) we could readily demonstrate expression of the VZV gpI antigen at 3-4 days after VZV infection. (E)-5-(2-Bromovinyl)-2'-deoxyuridine (BVDU), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine (HPMPA) and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine (HPMC) were shown to be potent inhibitors of VZV replication by this assay. HPMPA and HPMPC were also active against thymidine kinase-deficient (TK-) VZV whereas BVDU was not. The flow cytometric method based on the use of mAb VL8 may be of considerable help for the early diagnosis of VZV infection and evaluation of viral sensitivity to antiviral drugs.
authors.affiliation: Rega Institute for Medical Research, Katholieke Universiteit Leuven, Belgium.
authors.forename: R
authors.initials: R
authors.lastname: Snoeck
authors.forename: D
authors.initials: D
authors.lastname: Schols
authors.forename: C
authors.initials: C
authors.lastname: Sadzot-Delvaux
authors.forename: J M
authors.initials: JM
authors.lastname: Cloes
authors.forename: G
authors.initials: G
authors.lastname: Andrei
authors.forename: E
authors.initials: E
authors.lastname: De Clercq
authors.forename: J
authors.initials: J
authors.lastname: Piette
authors.forename: B
authors.initials: B
authors.lastname: Rentier
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D000998:Antiviral Agents / Q000494:pharmacology; D002478:Cells, Cultured; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives / Q000494:pharmacology; D003856:Deoxyuracil Nucleotides / Q000494:pharmacology; D004341:Drug Evaluation; D005434:Flow Cytometry; D014645:Herpesvirus 3, Human / Q000254:growth & development / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D063065:Organophosphonates; D009943:Organophosphorus Compounds / Q000494:pharmacology; D013937:Thymidine Kinase / Q000172:deficiency; D014759:Viral Envelope Proteins / Q000276:immunology* / Q000302:isolation & purification; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; D003856:Deoxyuracil Nucleotides; D063065:Organophosphonates; D009943:Organophosphorus Compounds; D014759:Viral Envelope Proteins; C056913:glycoprotein E, varicella-zoster virus; C033642:5-(2-bromovinyl)-2'-deoxyuridine-5'-triphosphate; D003596:Cytosine; C050127:9-(S)-(3-hydroxy-2-(phosphonomethoxy)propyl)adenine; D013937:Thymidine Kinase; D000225:Adenine; D000077404:Cidofovir