The S Genome Segment Is Sufficient to Maintain Pathogenicity in Intra-Clade Lassa Virus Reassortants in a Guinea Pig Model

Welch, Stephen R.; Scholte, Florine E. M.; Albariño, César G.; Kainulainen, Markus H.; Coleman-McCray, JoAnn D.; Guerrero, Lisa Wiggleton; Chakrabarti, Ayan K.; Klena, John D.; Nichol, Stuart T.; Spengler, Jessica R.; Spiropoulou, Christina F.

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The S Genome Segment Is Sufficient to Maintain Pathogenicity in Intra-Clade Lassa Virus Reassortants in a Guinea Pig Model

Supporting Files

July 11 2018
By Welch, Stephen R. ; Scholte, Florine E. M. ; Albariño, César G. ; ...

File Language:

English

Details

Alternative Title:

Front Cell Infect Microbiol
Personal Author:

Welch, Stephen R. ; Scholte, Florine E. M. ; Albariño, César G. ; Kainulainen, Markus H. ; Coleman-McCray, JoAnn D. ; Guerrero, Lisa Wiggleton ; Chakrabarti, Ayan K. ; Klena, John D. ; Nichol, Stuart T. ; Spengler, Jessica R. ; Spiropoulou, Christina F.
Description:

Genome reassortment in Lassa virus (LASV) has been reported in nature, but phenotypic consequences of this phenomenon are not well described. Here we characterize, both | and |, reassortment between 2 LASV strains: the prototypic 1976 Josiah strain and a more recently isolated 2015 Liberian strain. | analysis showed that although cis- and trans-acting elements of viral RNA synthesis were compatible between strains, reassortants demonstrated different levels of viral replication. These differences were also apparent |, as reassortants varied in pathogenicity in the guinea pig model of LASV infection. The reassortant variant containing the Josiah S segment retained the virulence of the parental Josiah strain, but the reassortant variant containing the S segment of the Liberian isolate was highly attenuated compared to both parental strains. Contrary to observations in reassortants between LASV and other arenavirus species, which suggest that L segment-encoded factors are responsible for virulence, these studies highlight a role for S segment-encoded virulence factors in disease, and also suggest that inefficient interactions between proteins of heterologous strains may limit the prevalence of reassortant LASV variants in nature.
Subjects:

Animals Disease Models, Animal Guinea Pigs Lassa Fever Reassortant Viruses Virulence Virulence Factors Virus Replication
Source:

Front Cell Infect Microbiol. 2018; 8
Pubmed ID:

30050872
Pubmed Central ID:

PMC6050391
Document Type:

Journal Article
Funding:

R01 AI109008/AI/NIAID NIH HHS/United States
Volume:

8
Collection(s):

CDC Public Access
Main Document Checksum:

urn:sha256:8b482cd72bcff666ea8935163c6154ed3721e64e4fae8fc55ab6292948133686
Download URL:

https://stacks.cdc.gov/view/cdc/89847/cdc_89847_DS1.pdf
File Type:

[PDF - 7.16 MB ]

File Language:

English

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