Journal article
Point mutation in the glycoprotein of lymphocytic choriomeningitis virus is necessary for receptor binding, dendritic cell infection, and long-term persistence
Proceedings of the National Academy of Sciences - PNAS, Vol.108(7), pp.2969-2974
02/15/2011
DOI: 10.1073/pnas.1019304108
PMCID: PMC3041138
PMID: 21270335
Abstract
Arenaviruses are a major cause of hemorrhagic fevers endemic to Sub-Saharan Africa and South America, and thus a major public health and medical concern. The prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) is widely used as a model system for studying persistent and acute infections, as well as for gaining an understanding of mammalian immune function. When originally characterized three decades ago, the LCMV isolate, Armstrong, which causes an acute infection in adult mice, was found to differ from the LCMV Clone 13 strain that causes a persistent infection by two amino acid changes, one within the virus surface glycoprotein (GP1: F260L) and the other within the virus L polymerase (K1076Q). Mutation F260L was considered solely responsible for the exceptionally strong binding affinity of Clone 13 (L at GP1 260) to its cellular receptor, α-dystroglycan, which among cells of the immune system is preferentially expressed on dendritic cells, and consequently, alters dendritic cell function leading to viral persistence. Recently, we noted a previously overlooked nucleotide difference between these two strains that results in an additional amino acid change in GP1, N176D. To investigate the potential contribution of this newly identified mutation to the Clone 13 phenotype, we used reverse-genetics approaches to generate recombinant LCM viruses with each of these individual mutations. Phenotypic characterization of these rLCMV showed that mutation F260L, but not N176D, in the GP1 of LCMV is essential for mediating the long-term persistence of Clone 13 infections. This work emphasizes the importance of subtle differences in viral strains that determine disease outcomes.
Details
- Title: Subtitle
- Point mutation in the glycoprotein of lymphocytic choriomeningitis virus is necessary for receptor binding, dendritic cell infection, and long-term persistence
- Creators
- Brian M Sullivan - Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, andSébastien F Emonet - Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, andMegan J Welch - Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, andAndrew M Lee - Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, andKevin P Campbell - The Howard Hughes Medical Institute, Department of Molecular Physiology and Biophysics, Departments of Neurology and Internal MedicineJuan C de la Torre - Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, andMichael B Oldstone - Viral-Immunobiology Laboratory, Department of Immunology and Microbial Science, and
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.108(7), pp.2969-2974
- DOI
- 10.1073/pnas.1019304108
- PMID
- 21270335
- PMCID
- PMC3041138
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 02/15/2011
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute
- Record Identifier
- 9984020877102771
Metrics
21 Record Views