Malays. Appl. Biol. (1997) 26(1): 25-32
ANTIVIRAL ACTIVITY OF (S)-9-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL) ADENINE (HPMPA) AGAINST EQUINE HERPESVIRUS TYPE-1 (EHV-1) IN MICE
MOHD-AZMI, ML.*1 and FIELD, H.J.2
1 Department of Veterinary Pathology & Microbiology, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor, Malaysia
2 Centre for Veterinary Science, Cambridge University Veterinary School, Madingley Road, Cambridge CBS OES, United Kingdom
ABSTRACT
The potential of (s)-9-(3-hydroxy-2-phosphonylmethoxypropyl) adenine (HPMPA) as a chemotherapeutic agent againsl equine herpesvirus type-1 (EHV-1) was studied in BALB/c mice. The results showed that prophylactic doses of HPMPA were more effective than therapeutic doses in reducing of EHV-1 replication in mice. Thus 60% mortality was noted in untreated-mice infected with EHV-1 but no mortality was observed when mice were treated prophylactically with HPMPA at a dose of 50 mg/kg/day beginning from 1 day before virus inoculation. Mice treated with HPMPA beginning from 1 day after virus inoculation exhibited 20% mortality; virus titres were reduced compared to untreated control but at a lower rate than those observed in the mice treated beginning from 1 day before virus inoculation. IgG antibody reponses were reduced following administration of HPMPA. Mice previously treated with HPMPA beginning from 1 day before virus inoculation and recovered from the disease were not fully protected upon a subsequent exposure to EHV-1. The protection was conferred in mice treated with HPMPA beginning from 1 day after primary virus inoculation and the untreated control. This study indicated that HPMPA is an effective chemotherapeutic antiviral agent, but prophylactic and therapeutic doses appeared to give undesired effects to subsequent IgG antibody responses and development of protective immunity against EHV-1.
ABSTRAK
Potensi (s)-9-(3-hidroksi-2-fosfonimetoksipropil) adenin (HPMPA) sebagai agen terapikimia terhadap virus herpes ekuin tip-1 (EHV-1) di kaji pada mencit BALB/c. Keputusan menunjukkan bahawa dos profilaksis HPMPA lebih berkesan daripada dos terapeutik bagi mengurangkan pengreplikatan EHV-1 dalam mencit. Mortaliti sebanyak 60% dicatat pada mencit tak dirawat yang dijangkiti dengan EHV-1 tetapi tiada mortaliti berlaku apabila mencit dirawat secara profilaksis dengan HPMPA pada dos 50 mg/kg/sehari bermula daripada 1 hari sebelum penginoculatan virus. Mencit yang dirawat dengan HPMPA bermula dari 1 hari selepas penginokulatan virus mempamerkan mortaliti sebanyak 20%; liter virus berkurang berbanding dengan kawalan yang tidak dirawat tetapi pada kadar yang lebih rendah daripada yang ditunjukkan oleh mencit yang mula dirawat mulai dari 1 hari sebelum penginokulatan virus. Gerakbalas antibodi IgG berkurang berikutan pemberian HPMPA. Mencit yang terdahulunya dirawat dengan HPMPA mulai dari 1 hari selepas penginokulatan primer virus dan sembuh daripada penyakit tidak terlindung sepenuhnya terhadap suatu pendedahan berikut EHV-1. Perlindungan berlaku pada mencit yang dirawat dengan HPMPA mulai dari 1 hari sebelum penginokulatan primer virus dan kawalan tidak dirawat. Kajian ini menunjukkan HPMPA adalah suatu agen antivirus terapikimia, tetapi dos profilaksis dan terapeutik kelihatan memberikan kesan buruk kepada gerakbalas antibodi IgG dan pengembangan keimunijR berikutnya terhadap EHV-1.
Key words: Antibody response, EHV-1, HPMPA, protection, viremia
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