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 Fingerote, R. J. Articles by Levy, G. A. Search for Related Content PubMed PubMed Citation Articles by Fingerote, R. J. Articles by Levy, G. A. Agricola Articles by Fingerote, R. J. Articles by Levy, G. A.

A 2',5'-oligoadenylate analogue inhibits murine hepatitis virus strain 3 (MHV-3) replication in vitro but does not reduce MHV-3-related mortality or induction of procoagulant activity in susceptible mice

¹ Toronto General Hospital, Norman Urquhart Wing 10-151, 621 University Avenue, Toronto, Ontario, Canada M5G 2C4
² Hahnemann University, Philadelphia
and³ Temple University, Philadelphia, Pennsylvania, USA

Exposure of inbred mice to murine hepatitis virus strain 3 (MHV-3) causes a strain dependent spectrum of disease symptoms which correlates with induction of procoagulant activity (PCA) by macrophages. Previous studies have demonstrated a role for interferons in resistance to MHV-3 infection. These cytokines have both antiviral and immunoregulatory effects which may be crucial for MHV-3 resistance. One of their antiviral effects is the ability to induce 2',5'-oligoadenylate (2-5A) synthetase leading to activation of the latent endoribonuclease RNase L. Once activated, RNase L degrades ssRNA thereby inhibiting viral-induced protein synthesis. These studies were undertaken to determine the effects of Oragen 0004 (Oragen), an RNase L activating 2-5A analogue, on MHV-3 replication and induction of PCA in vitro and on the course of MHV-3 infection in susceptible BALB/cJ mice in vivo. Oragen inhibited MHV-3 replication in peritoneal macrophages derived from resistant A/J and susceptible BALB/cJ mice in a dose-dependent fashion. Concentrations of Oragen greater than 110 µg/2 x 10⁶ macrophages decreased viral replication by greater than 89% in peritoneal macrophages in vitro obtained from both BALB/cJ and A/J mice and by 86% in livers from MHV-3-infected mice in vivo. However, Oragen failed to inhibit induction of PCA following in vitro exposure of BALB/cJ mice-derived peritoneal macrophages to MHV-3 and failed to prevent the development of fulminant hepatitis in BALB/cJ mice in vivo. Thus, these studies demonstrate clearly that induction of 2-5A synthase and inhibition of viral replication is not sufficient to prevent MHV-3-related hepatocellular injury, and these data further support the role of PCA in the pathogenesis of MHV-3 infection.

^* Author for correspondence. Fax +1 416 340 3492. e-mail GLEVY@GPU.UTCC.UTORONTO.CA

Received 23 May 1994; accepted 16 September 1994.

This article has been cited by other articles:

				B. W. Neuman, D. A. Stein, A. D. Kroeker, A. D. Paulino, H. M. Moulton, P. L. Iversen, and M. J. Buchmeier Antisense Morpholino-Oligomers Directed against the 5' End of the Genome Inhibit Coronavirus Proliferation and Growth{dagger} J. Virol., June 1, 2004; 78(11): 5891 - 5899. [Abstract] [Full Text] [PDF]