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Antimicrobial Agents and Chemotherapy, June 2005, p. 2378-2386, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2378-2386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Interferon Alfacon-1 Protects Hamsters from Lethal Pichinde Virus Infection

Brian B. Gowen,1* Dale L. Barnard,1 Donald F. Smee,1 Min-Hui Wong,1 Anne M. Pace,1 Kie-Hoon Jung,1 Scott G. Winslow,1 Kevin W. Bailey,1 Lawrence M. Blatt,2 and Robert W. Sidwell1

Institute for Antiviral Research, Utah State University, Logan, Utah,1 InterMune, Brisbane, California2

Received 5 November 2004/ Returned for modification 29 December 2004/ Accepted 11 February 2005

Hemorrhagic fever of arenaviral origin is a frequently fatal infectious disease of considerable priority to the biodefense mission. Historically, the treatment of arenaviral infections with alpha interferons has not yielded favorable results. Here we present evidence that interferon alfacon-1, a nonnaturally occurring bioengineered alpha interferon approved for the treatment of chronic hepatitis C, is active against Pichinde and Tacaribe arenaviruses in cell culture. In the hamster model of Pichinde virus (PCV) infection, interferon alfacon-1 treatment significantly protected animals from death, prolonged the survival of those that eventually died, reduced virus titers, and limited liver damage characteristic of PCV-induced disease. Moreover, interferon alfacon-1 also demonstrated therapeutic activity, to a lesser degree, when the initiation of treatment was delayed up to 2 days post-virus challenge. Despite the observed advantages of interferon alfacon-1 therapy, efforts to stimulate the immune system with the known interferon inducer poly(I:C12U) (Ampligen) offered only limited protection against lethal PCV challenge. Taken together, these data suggest that the increased potency of the bio-optimized interferon alfacon-1 molecule may be critical to the observed antiviral effects. These data are the first report demonstrating efficacious treatment of acute arenaviral disease with alpha interferon therapy, and further study is warranted.

* Corresponding author. Mailing address: Institute for Antiviral Research, 5600 Old Main Hill, Utah State University, Logan, UT 84322. Phone: (435) 797-3112. Fax: (435) 797-3959. E-mail: bgowen{at}cc.usu.edu.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2378-2386, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2378-2386.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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