HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Roberts, J. Articles by McGregor, W. G. Search for Related Content PubMed PubMed Citation Articles by Roberts, J. Articles by McGregor, W. G. Agricola Articles by Roberts, J. Articles by McGregor, W. G.

Inhibition of mouse retroviral disease by bioactive glutaminase-asparaginase

W. Glenn McGregor

Department of Basic Pharmaceutical Sciences, College of Pharmacy, The University of South Carolina, Columbia, South Carolina 29208, U.S.A.

Glutamine depletion strongly inhibits the replication of Rauscher murine leukaemia retrovirus (RLV) in vitro. Pseudomonas 7A glutaminase-asparaginase (PGA), capable of depleting glutamine and asparagine for prolonged periods, was used to determine the therapeutic effectiveness of glutamine depletion in mice infected with RLV or Friend virus. During PGA treatment of viraemic animals, serum reverse transcriptase activity fell to control levels and infected animals did not develop splenomegaly. The therapeutic results obtained with PGA compared favourably with those of azidothymidine given intraperitoneally at 30 mg/kg/day. Western blots performed on splenic tissue from control and treated animals indicated that glutamine depletion prevented readthrough of an amber codon at the gag-pol junction, stopping translation of viral mRNA at that point. Treatment of RLV-infected animals with PGA resulted in nearly a 200% increase in mean survival time even when therapy was initiated late in the course of the disease. To our knowledge, this is the first demonstration that a nutrient required for viral replication can be enzymically depleted in vivo to inhibit viral replication.

Present address: Carcinogenesis Laboratory, Department of Microbiology and Department of Biochemistry Michigan State University, East Lansing, Michigan 48824, U.S.A.

Received 18 July 1990; accepted 18 October 1990.

This article has been cited by other articles:

				A. Spittler, R. Oehler, P. Goetzinger, S. Holzer, C. M. Reissner, F. Leutmezer, V. Rath, F. Wrba, R. Fuegger, G. Boltz-Nitulescu, et al. Low Glutamine Concentrations Induce Phenotypical and Functional Differentiation of U937 Myelomonocytic Cells J. Nutr., November 1, 1997; 127(11): 2151 - 2157. [Abstract] [Full Text]