Competing pathways control host resistance to virus via tRNA modification and programmed ribosomal frameshifting

Molecular Systems Biology

Nathaniel D Maynard²  Derek N Macklin²  Karla Kirkegaard¹ 

[1] Department of Microbiology and Immunology, Stanford University, Stanford, CA, USA;Department of Bioengineering, Stanford University, Stanford, CA, USA

关键词: bacteriophage lambda;    host‐virus;    iron‐sulfur clusters;    programmed ribosomal frameshifting;    tRNA modification;   

DOI  :  10.1038/msb.2011.101

来源: Wiley

【 摘 要 】

Abstract

Viral infection depends on a complex interplay between host and viral factors. Here, we link host susceptibility to viral infection to a network encompassing sulfur metabolism, tRNA modification, competitive binding, and programmed ribosomal frameshifting (PRF). We first demonstrate that the iron-sulfur cluster biosynthesis pathway in Escherichia coli exerts a protective effect during lambda phage infection, while a tRNA thiolation pathway enhances viral infection. We show that tRNA^Lys uridine 34 modification inhibits PRF to influence the ratio of lambda phage proteins gpG and gpGT. Computational modeling and experiments suggest that the role of the iron-sulfur cluster biosynthesis pathway in infection is indirect, via competitive binding of the shared sulfur donor IscS. Based on the universality of many key components of this network, in both the host and the virus, we anticipate that these findings may have broad relevance to understanding other infections, including viral infection of humans.

Synopsis

Viral infection depends on a complex interplay between host and viral factors. Here, the authors link host susceptibility to viral infection to a network encompassing sulfur metabolism, tRNA modification, competitive binding, and programmed ribosomal frameshifting.

• The iron-sulfur cluster biosynthesis pathway in Escherichia coli exerts a protective effect during lambda phage infection, while a tRNA thiolation pathway enhances viral infection.
• tRNALys uridine 34 modification inhibits programmed ribosomal frameshifting to influence the ratio of lambda phage proteins gpG and gpGT.
• The role of the iron-sulfur cluster biosynthesis pathway in infection is indirect, via competitive binding of the shared sulfur donor IscS.
• Based on the universality of many key components of this network, in both the host and the virus, these findings may have broad relevance to understanding other infections, including viral infection of humans.

【 授权许可】

CC BY-NC-SA   
Copyright © 2012 EMBO and Macmillan Publishers Limited

Creative Commons Attribution License, which permits distribution, and reproduction in any medium, provided the original author and source are credited. This license does not permit commercial exploitation without specific permission.