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PMID: 2158102 Published · ppublish English Journal Article

Suppression of feline immunodeficiency virus infection in vivo by 9-(2-phosphonomethoxyethyl)adenine.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 87 ·No. 8 ·1990-04-00 ·Pages 3087-91

Egberink H, Borst M, Niphuis H, Balzarini J, Neu H, Schellekens H, De Clercq E, Horzinek M, Koolen M

Abstract

The acyclic purine nucleoside analogue 9-(2-phosphonomethoxyethyl)adenine [PMEA; formerly referred to as 9-(2-phosphonylmethoxyethyl)adenine] is a potent and selective inhibitor of human immunodeficiency virus replication in vitro and of Moloney murine sarcoma virus-induced tumor formation in mice. In the latter system PMEA has stronger antiretroviral potency and selectivity than 3'-azido-3'-thymidine (AZT). We have now investigated the effect of the drug in cats infected with the feline immunodeficiency virus (FIV). In vitro, PMEA was found to efficiently block FIV replication in feline thymocytes (50% effective dose, 0.6 microM). When administered to cats at doses of 20, 5, or 2 mg/kg per day, PMEA caused a dose-dependent suppression of FIV replication and virus-specific antibody production. Seropositive field cats with signs of opportunistic infection (gingivitis, stomatitis, and diarrhea) showed clinical improvement during PMEA therapy (5 mg/kg per day) and recurrence of the disease after treatment was discontinued. Thus, FIV infection in cats is an excellent model to test the efficacy of selective anti-human immunodeficiency virus agents in vivo.

MeSH Terms
Adenine/analogs & derivatives,pharmacology,therapeutic use Animals Antiviral Agents/therapeutic use Cats Cell Line HIV/drug effects,physiology Immunologic Deficiency Syndromes/complications,drug therapy,microbiology Opportunistic Infections/prevention & control Organophosphonates Retroviridae/drug effects,growth & development,physiology Retroviridae Infections/complications,drug therapy,microbiology T-Lymphocytes/microbiology Virus Replication/drug effects Zidovudine/pharmacology
Chemicals
Antiviral Agents Organophosphonates Zidovudine adefovir Adenine
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Egberink H
Department of Infectious Diseases and Immunology, School of Veterinary Medicine, State University of Utrecht, The Netherlands.
Borst M
Niphuis H
Balzarini J
Neu H
Schellekens H
De Clercq E
Horzinek M
Koolen M
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.87.8.3087
Published
1990-04-00
Pages
3087-91
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC53839
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.87.8.3087 PMC Full Text View journal details
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