Prophylactic and therapeutic intervention of Punta Toro virus (Phlebovirus, Bunyaviridae) infection in hamsters with interferon alfacon-1.
Punta Toro virus (PTV) is a member of the Bunyaviridae family, genus Phlebovirus, related to the highly pathogenic Rift Valley fever virus (RVFV). It produces a disease in hamsters that models severe Rift Valley fever (RVF) in humans. The recent outbreak of RVF in Kenya stresses the need to identify prophylactic and therapeutic measures for preventing and treating severe forms of disease. To this end, interferon (IFN) alfacon-1 (consensus IFN-alpha) was evaluated in cell culture against RVFV and PTV, and in the hamster PTV infection model. Survival outcome following treatment initiated pre- and post-virus challenge and the suppression of viral burden and liver disease in infected hamsters was determined. Pre-treatment of cell cultures with IFN alfacon-1 induced marked antiviral activity against both viruses. Intraperitoneal treatment of hamsters initiated 4 h prior to infection with PTV was highly protective and greatly limited liver disease and systemic and liver viral burden. Complete protection from a highly lethal challenge dose was afforded by treatment initiated 36 h following viral inoculation. Although efficacy was much reduced, IFN alfacon-1 therapy was still beneficial when started as late as 3-5 days post-virus exposure. These studies suggest that IFN alfacon-1 may be an effective treatment for early intervention following infection with RVFV.
Gowen
Brian B
BB
Institute for Antiviral Research and Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT 84322-5600, USA. bgowen@cc.usu.edu
Wong
Min-Hui
MH
Jung
Kie-Hoon
KH
Blatt
Lawrence M
LM
Sidwell
Robert W
RW
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D002044:Bunyaviridae Infections / Q000188:drug therapy* / Q000276:immunology / Q000517:prevention & control*; D002460:Cell Line; D002470:Cell Survival; D006224:Cricetinae; D005260:Female; D000882:Haplorhini; D007370:Interferon Type I / Q000494:pharmacology / Q000627:therapeutic use*; D016898:Interferon-alpha; D007565:Jaundice / Q000821:virology; D008099:Liver / Q000821:virology; D008647:Mesocricetus; D016856:Phlebovirus / Q000187:drug effects*; D011994:Recombinant Proteins; D012296:Rift Valley fever virus / Q000187:drug effects; D044967:Serum / Q000821:virology; D016019:Survival Analysis; D016896:Treatment Outcome
D000998:Antiviral Agents; D007370:Interferon Type I; D016898:Interferon-alpha; D011994:Recombinant Proteins; C050739:interferon alfacon-1; D000410:Alanine Transaminase