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Genomic and biological characterization of aggressive and docile strains of lymphocytic choriomeningitis virus rescued from a plasmid-based reverse-genetics system

Minjie Chen^1,

Shuiyun Lan^1,

Rong Ou^1,

Graeme E. Price^1,,

¹ Center for Molecular Chaperones/Radiobiology and Cancer Virology, Medical College of Georgia, Augusta, GA 30912, USA
² Molecular Integrative Neuroscience Department (MIND), The Scripps Research Institute, La Jolla, CA 92037, USA

Correspondence
Demetrius Moskophidis
dmoskophidis{at}mcg.edu

Arenaviruses include several causative agents of haemorrhagic fever disease in humans. In addition, the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is a superb model for the study of virus–host interactions, including the basis of viral persistence and associated diseases. There is little understanding about the molecular mechanisms concerning the regulation and specific role of viral proteins in modulating arenavirus–host cell interactions either associated with an acute or persistent infection, and associated disease. Here, we report the genomic and biological characterization of LCMV strains ‘Docile’ (persistent) and ‘Aggressive’ (not persistent) recovered from cloned cDNA via reverse genetics. Our results confirmed that the cloned viruses accurately recreated the in vivo phenotypes associated with the corresponding natural Docile and Aggressive viral isolates. In addition, we provide evidence that the ability of the Docile strain to persist is determined by the nature of both S and L RNA segments. Thus, our findings provide the foundation for studies aimed at gaining a detailed understanding of viral determinants of LCMV persistence in its natural host, which may aid in the development of vaccines to prevent or treat the diseases caused by arenaviruses in humans.

These authors contributed equally to this work.

Present address: Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration, 1401 Rockville Pike HFM 730, Rockville, MD 20852-1448, USA.

Supplementary material is available with the online version of this paper.