Phosphonylmethoxyalkyl purine and pyrimidine derivatives for treatment of opportunistic cytomegalovirus and herpes simplex virus infections in murine AIDS.

Journal Article (Journal Article)

Murine acquired immunodeficiency syndrome (MAIDS) was induced in C57BL/6 mice following infection with the LP-BM5 retrovirus complex. Infected mice developed splenomegaly, lymphadenopathy and loss of B- and T-cell functions 100 days after virus inoculation. Mice with AIDS were highly susceptible to opportunistic murine cytomegalovirus (MCMV) and herpes simplex virus (HSV-1) infections. The therapeutic activities of two phosphonylmethoxyalkyl derivatives, 9-(2-phosphonylmethoxyethyl)adenine (PMEA) and (S)-1-(3-hydroxy-2-phosphonylmethoxy-propyl)cytosine (HPMPC), were evaluated in MAIDS immunosuppressed mice infected with MCMV or HSV-1. MCMV infection resulted in extensive viral replication in lung, liver and spleen and death occurred five to twelve days post-infection. Treatment with either HPMPC or ganciclovir (DHPG) reduced mortality and viral replication in target organs; however, HPMPC was as effective as DHPG at one-fifth the DHPG dose. Moreover, when a single dose (100 mg/kg) of HPMPC was administered 24 h prior to MCMV infection, it suppressed virus replication at seven and 14 days post-infection, thus resulting in a significant prolongation of life. PMEA was effective against opportunistic HSV-1 infections, but appeared to be less effective than HPMPC against MCMV infections. These results indicate that MAIDS can be used as a model for evaluating antivirals in an immunocompromised host, and suggest that both PMEA and HPMPC may be useful in the treatment of opportunistic CMV and HSV-1 infections.

Full Text

Duke Authors

Cited Authors

  • De Castro, LM; Kern, ER; De Clercq, E; Ghaffar, A; Mayer, EP; Vogt, PE; Gangemi, JD

Published Date

  • July 1991

Published In

Volume / Issue

  • 16 / 1

Start / End Page

  • 101 - 114

PubMed ID

  • 1663726

International Standard Serial Number (ISSN)

  • 0166-3542

Digital Object Identifier (DOI)

  • 10.1016/0166-3542(91)90062-v

Language

  • eng

Conference Location

  • Netherlands