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Journal of Virology, July 2009, p. 6357-6362, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00019-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Development of Infectious Clones for Virulent and Avirulent Pichinde Viruses: a Model Virus To Study Arenavirus-Induced Hemorrhagic Fevers {triangledown} ,{dagger}

Shuiyun Lan, Lisa McLay Schelde, Jialong Wang, Naveen Kumar, Hinh Ly,* and Yuying Liang*

Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322

Received 5 January 2009/ Accepted 15 April 2009

Several arenaviruses can cause hemorrhagic fever diseases (VHFs) in humans, the pathogenic mechanism of which is poorly understood due to their virulent nature and the lack of molecular clones. A safe, convenient, and economical small animal model of arenavirus hemorrhagic fever is based on guinea pigs infected by the arenavirus Pichinde (PICV). PICV does not cause disease in humans, but an adapted strain of PICV (P18) causes a disease in guinea pigs that mimics arenavirus hemorrhagic fever in humans in many aspects, while a low-passaged strain (P2) remains avirulent in infected animals. In order to identify the virulence determinants within the PICV genome, we developed the molecular clones for both the avirulent P2 and virulent P18 viruses. Recombinant viruses were generated by transfecting plasmids that contain the antigenomic L and S RNA segments of PICV under the control of the T7 promoter into BSRT7-5 cells, which constitutively express T7 RNA polymerase. By analyzing viral growth kinetics in vitro and virulence in vivo, we show that the recombinant viruses accurately recapitulate the replication and virulence natures of their respective parental viruses. Both parental and recombinant virulent viruses led to high levels of viremia and titers in different organs of the infected animals, whereas the avirulent viruses were effectively controlled and cleared by the hosts. These novel infectious clones for the PICV provide essential tools to identify the virulence factors that are responsible for the severe VHF-like disease in infected animals.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322. Phone: (404) 727-3243. Fax: (404) 727-8538. E-mail for Yuying Liang: yliang5{at}emory.edu. E-mail for Hinh Ly: hly{at}emory.edu

{triangledown} Published ahead of print on 22 April 2009.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, July 2009, p. 6357-6362, Vol. 83, No. 13
0022-538X/09/$08.00+0     doi:10.1128/JVI.00019-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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