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Effect of several antiviral agents on human lymphocyte functions and marrow progenitor cell proliferation
Abstract:
Toxicity to hematopoiesis and lymphocytic function are major considerations in the clinical applicability of antiviral agents. We have examined the toxicities of five antiviral agents showing activity against herpesviruses: vidarabine, acyclovir, (E)-5-(2-bromovinyl)-2'-deoxyuridine, trifluorothymidine, and (S)-9-(2,3-dihydroxypropyl)adenine. The drugs were tested in vitro for inhibition of herpes simplex virus type 1 and human cytomegalovirus replication, effects on marrow progenitor cell growth, effects on lymphocyte responses to mitogen and alloantigen stimulation, and effects on several lymphocyte cytotoxic responses. In general, lymphocyte proliferative responses were inhibited by the various drugs at lower concentrations than were cytotoxic activities. Acyclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine were the least toxic drugs tested, with antiviral indices exceeding 10,000. Vidarabine and trifluorothymidine were more toxic, with antiviral indices generally between 10 and 100. (S)-9-(2,3-dihydroxypropyl)-adenine was the most toxic, with several antiviral indices between 1 and 10.
Insights
This study evaluated five antiviral drugs for herpesvirus infections, assessing their toxicity to blood cell production and immune cell function. Acyclovir and (E)-5-(2-bromovinyl)-2'-deoxyuridine demonstrated the lowest toxicity, making them promising candidates for clinical use.
Area of Science:
- Virology
- Immunology
- Toxicology
Background:
- Clinical use of antiviral drugs requires understanding their impact on hematopoiesis and immune function.
- Herpesviruses pose significant health challenges, necessitating effective and safe antiviral therapies.
Purpose of the Study:
- To evaluate the in vitro toxicity of five antiviral agents against herpes simplex virus type 1 and human cytomegalovirus.
- To compare the effects of these antivirals on hematopoietic progenitor cells and various lymphocyte functions.
Main Methods:
- In vitro testing of five antiviral drugs: vidarabine, acyclovir, (E)-5-(2-bromovinyl)-2 '-deoxyuridine, trifluorothymidine, and (S)-9-(2,3-dihydroxypropyl)adenine.
- Assessed inhibition of viral replication, effects on marrow progenitor cell growth, and impacts on lymphocyte proliferation, mitogen responses, and cytotoxic activities.
Main Results:
- Lymphocyte proliferation was generally more sensitive to drug inhibition than cytotoxic activities.
- Acyclovir and (E)-5-(2-bromovinyl)-2 '-deoxyuridine exhibited high antiviral indices (>10,000), indicating low toxicity.
- Vidarabine and trifluorothymidine showed moderate toxicity (antiviral indices 10-100), while (S)-9-(2,3-dihydroxypropyl)adenine was the most toxic (antiviral indices 1-10).
Conclusions:
- Acyclovir and (E)-5-(2-bromovinyl)-2 '-deoxyuridine are the safest antiviral agents among those tested for herpesvirus infections.
- Drug toxicity varies significantly, impacting the clinical applicability of antiviral therapies for hematologic and immunologic safety.