Mutations of the segment-specific nucleotides at the 3' end of influenza virus NS segment control viral replication

[tetano]

Virology. 2019 Nov 1;539:104-113. doi: 10.1016/j.virol.2019.10.015. [Epub ahead of print] Mutations of the segment-specific nucleotides at the 3' end of influenza virus NS segment control viral replication.

Rodriguez P¹, Marcos-Villar L¹, Zamarre?o N¹, Y?ng?ez E¹, Nieto A².
Author information

1 Centro Nacional de Biotecnolog?a, C.S.I.C. Darwin 3, Cantoblanco, 28049, Madrid, Spain; CIBER de Enfermedades Respiratorias CIBERES, Spain. 2 Centro Nacional de Biotecnolog?a, C.S.I.C. Darwin 3, Cantoblanco, 28049, Madrid, Spain; CIBER de Enfermedades Respiratorias CIBERES, Spain. Electronic address: anieto@cnb.csic.es.

Abstract

The vRNAs of influenza A viruses contain 12 and 13 nucleotide-long sequences at their 3' and 5' termini respectively that are highly conserved and constitute the vRNA promoter. These sequences and the next three segment-specific nucleotides show inverted partial complementarity and are followed by several unpaired nucleotides of poorly characterized function at the 3' end. We have performed systematic point-mutations at the segment-specific nucleotides 15-18 of the 3'-end of a NS-like vRNA segment. All NS-like vRNAs containing mutations at position 15, and some at positions 16-18 showed reduced transcription/replication efficiency in a transfection/infection system. In addition, the replication of recombinant viruses containing mutations at position 15 was impaired both in single and multi-cycle experiments. This reduction was the consequence of a decreased expression of the NS segment. The data indicate that NS1 plays a role in the transcription/replication of its own segment, which elicits a global defect on virus replication.
Copyright ? 2019. Published by Elsevier Inc.


KEYWORDS:

Gene expression; Influenza virus; NS segment; Segment-specific nucleotides

PMID: 31706162 DOI: 10.1016/j.virol.2019.10.015