title: Interferon alfacon-1 protects hamsters from lethal pichinde virus infection.
abstract: 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.
authors.affiliation: Institute for Antiviral Research, 5600 Old Main Hill, Utah State University, Logan, UT 84322, USA. bgowen@cc.usu.edu
authors.forename: Brian B
authors.initials: BB
authors.lastname: Gowen
authors.forename: Dale L
authors.initials: DL
authors.lastname: Barnard
authors.forename: Donald F
authors.initials: DF
authors.lastname: Smee
authors.forename: Min-Hui
authors.initials: MH
authors.lastname: Wong
authors.forename: Anne M
authors.initials: AM
authors.lastname: Pace
authors.forename: Kie-Hoon
authors.initials: KH
authors.lastname: Jung
authors.forename: Scott G
authors.initials: SG
authors.lastname: Winslow
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Bailey
authors.forename: Lawrence M
authors.initials: LM
authors.lastname: Blatt
authors.forename: Robert W
authors.initials: RW
authors.lastname: Sidwell
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001117:Arenaviridae Infections / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology; D006477:Arenaviruses, New World / Q000187:drug effects; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D007370:Interferon Type I / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016898:Interferon-alpha; D018052:Pichinde virus / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; C050739:interferon alfacon-1