The 3′ Untranslated Regions of Influenza Genomic Sequences Are 5′PPP-Independent Ligands for RIG-I

Davis, William G.; Bowzard, J. Bradford; Sharma, Suresh D.; Wiens, Mayim E.; Ranjan, Priya; Gangappa, Shivaprakash; Stuchlik, Olga; Pohl, Jan; Donis, Ruben O.; Katz, Jacqueline M.; Cameron, Craig E.; Fujita, Takashi; Sambhara, Suryaprakash

doi:10.1371/journal.pone.0032661

i

The 3′ Untranslated Regions of Influenza Genomic Sequences Are 5′PPP-Independent Ligands for RIG-I

Supporting Files Public Domain

Mar 15 2012
By Davis, William G. ; Bowzard, J. Bradford ; Sharma, Suresh D. ; ...

File Language:

English

Details

Alternative Title:

PLoS One
Personal Author:

Davis, William G. ; Bowzard, J. Bradford ; Sharma, Suresh D. ; Wiens, Mayim E. ; Ranjan, Priya ; Gangappa, Shivaprakash ; Stuchlik, Olga ; Pohl, Jan ; Donis, Ruben O. ; Katz, Jacqueline M. ; Cameron, Craig E. ; Fujita, Takashi ; Sambhara, Suryaprakash
Description:

Retinoic acid inducible gene-I (RIG-I) is a key regulator of antiviral immunity. RIG-I is generally thought to be activated by ssRNA species containing a 5'-triphosphate (PPP) group or by unphosphorylated dsRNA up to ~300 bp in length. However, it is not yet clear how changes in the length, nucleotide sequence, secondary structure, and 5' end modification affect the abilities of these ligands to bind and activate RIG-I. To further investigate these parameters in the context of naturally occurring ligands, we examined RNA sequences derived from the 5' and 3' untranslated regions (UTR) of the influenza virus NS1 gene segment. As expected, RIG-I-dependent interferon-β (IFN-β) induction by sequences from the 5' UTR of the influenza cRNA or its complement (26 nt in length) required the presence of a 5'PPP group. In contrast, activation of RIG-I by the 3' UTR cRNA sequence or its complement (172 nt) exhibited only a partial 5'PPP-dependence, as capping the 5' end or treatment with CIP showed a modest reduction in RIG-I activation. Furthermore, induction of IFN-β by a smaller, U/A-rich region within the 3' UTR was completely 5'PPP-independent. Our findings demonstrated that RNA sequence, length, and secondary structure all contributed to whether or not the 5'PPP moiety is needed for interferon induction by RIG-I.
Subjects:

Binding Sites Cell Line DEAD-box RNA Helicases Genome, Viral Host-Pathogen Interactions Humans Influenza A Virus Interferon-beta Kinetics Ligands Nucleic Acid Conformation RNA, Viral Viral Nonstructural Proteins
Source:

PLoS One. 2012; 7(3).
Document Type:

Journal Article
Volume:

7
Issue:

3
Collection(s):

CDC Public Access
Main Document Checksum:

urn:sha256:129b7d50c32b32645fd1699726c5e0b2fa480bdd775df701bb25b006a24d8e25
Download URL:

https://stacks.cdc.gov/view/cdc/8163/cdc_8163_DS1.pdf
File Type:

[PDF - 967.15 KB ]

File Language:

English

ON THIS PAGE

Details Supporting Files

CDC STACKS serves as an archival repository of CDC-published products including scientific findings, journal articles, guidelines, recommendations, or other public health information authored or co-authored by CDC or funded partners.

As a repository, CDC STACKS retains documents in their original published format to ensure public access to scientific information.