Replication of Nonsegmented Negative Strand RNA Viruses

The influenza A virus genome is comprised of eight single-stranded negative-sense viral RNA (vRNA) segments. Each of the eight vRNA segments contains segment-specific nonconserved noncoding regions (NCRs) of similar sequence and length in different influenza A virus strains. However, in the subtype-determinant segments, encoding haemagglutinin (HA) and neuraminidase (NA), the segment-specific noncoding regions are subtype-specific, varying significantly in sequence and length at both the 3´ and 5´ termini among different subtypes. The significance of these subtype-specific noncoding regions (ssNCR) in the influenza virus replication cycle is not fully understood. In this study, we show that truncations of the 3´-end H1-subtype-specific noncoding region (H1-ssNCR) resulted in recombinant viruses with decreased HA vRNA replication and attenuated growth phenotype, although the vRNA replication was not affected in single-template RNP reconstitution assays. The attenuated viruses were unstable and point mutations at nucleotide position 76 or 56 in the adjacent coding region of HA vRNA were found after serial passage. The mutations restored the HA vRNA replication and reversed the attenuated virus growth phenotype. We propose that the terminal noncoding and adjacent coding regions act synergistically to ensure optimal levels of HA vRNA replication in a multi-segment environment. These results, provide novel insights into the role of the 3´-end nonconserved noncoding regions and adjacent coding regions on template preference in multiple-segmented negative-strand RNA viruses. IMPORTANCE While most influenza A virus vRNA segments contain segment-specific nonconserved noncoding regions of similar length and sequence, these regions vary considerably both in length and sequence in the segments encoding HA and NA, the two major antigenic determinants of influenza A viruses. In this study, we investigated the function of the 3´-end H1-ssNCR and observed a synergistic effect between the 3´-end H1-ssNCR nucleotides and adjacent coding nucleotide(s) of HA segment on template preference in a multi-segment environment. The results unravel an additional level of complexity in the regulation of RNA replication in multiple-segmented negative-strand RNA viruses.

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Transcription and Replication of Nonsegmented Negative-Strand RNA Viruses

Current Topics in Microbiology and Immunology - Biology of Negative Strand RNA Viruses: The Power of Reverse Genetics ◽

10.1007/978-3-662-06099-5_3 ◽

2004 ◽

pp. 61-119 ◽

Cited By ~ 52

Author(s):

S. P. J. Whelan ◽

J. N. Barr ◽

G. W. Wertz

Keyword(s):

Rna Viruses ◽

Negative Strand ◽

Transcription And Replication

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Processing of Genome 5′ Termini as a Strategy of Negative-Strand RNA Viruses to Avoid RIG-I-Dependent Interferon Induction

PLoS ONE ◽

10.1371/journal.pone.0002032 ◽

2008 ◽

Vol 3 (4) ◽

pp. e2032 ◽

Cited By ~ 198

Author(s):

Matthias Habjan ◽

Ida Andersson ◽

Jonas Klingström ◽

Michael Schümann ◽

Arnold Martin ◽

...

Keyword(s):

Rna Viruses ◽

Negative Strand ◽

Interferon Induction

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Special Issue “Recent Advances in Morbillivirus Vaccine Development and Oncolytic Virotherapy”

Viruses ◽

10.3390/v12030341 ◽

2020 ◽

Vol 12 (3) ◽

pp. 341

Author(s):

Liang-Tzung Lin

Keyword(s):

Vaccine Development ◽

Rna Viruses ◽

Oncolytic Virotherapy ◽

Special Issue ◽

Negative Strand ◽

Recent Advances

Members of the Morbillivirus genus are enveloped, negative-strand RNA viruses that include a number of highly contagious pathogens important to humans and animals [...]

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Re-assessing the diversity of negative strand RNA viruses in insects

PLoS Pathogens ◽

10.1371/journal.ppat.1008224 ◽

2019 ◽

Vol 15 (12) ◽

pp. e1008224 ◽

Cited By ~ 16

Author(s):

Simon Käfer ◽

Sofia Paraskevopoulou ◽

Florian Zirkel ◽

Nicolas Wieseke ◽

Alexander Donath ◽

...

Keyword(s):

Rna Viruses ◽

Negative Strand

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Double-Stranded RNA Is Produced by Positive-Strand RNA Viruses and DNA Viruses but Not in Detectable Amounts by Negative-Strand RNA Viruses

Journal of Virology ◽

10.1128/jvi.80.10.5059-5064.2006 ◽

2006 ◽

Vol 80 (10) ◽

pp. 5059-5064 ◽

Cited By ~ 578

Author(s):

Friedemann Weber ◽

Valentina Wagner ◽

Simon B. Rasmussen ◽

Rune Hartmann ◽

Søren R. Paludan

Keyword(s):

Viral Infections ◽

Rna Viruses ◽

Innate Immune ◽

Genome Replication ◽

Dna Viruses ◽

Double Stranded Rna ◽

Positive Strand ◽

Negative Strand ◽

A Genome ◽

Positive Strand Rna

ABSTRACT Double-stranded RNA (dsRNA) longer than 30 bp is a key activator of the innate immune response against viral infections. It is widely assumed that the generation of dsRNA during genome replication is a trait shared by all viruses. However, to our knowledge, no study exists in which the production of dsRNA by different viruses is systematically investigated. Here, we investigated the presence and localization of dsRNA in cells infected with a range of viruses, employing a dsRNA-specific antibody for immunofluorescence analysis. Our data revealed that, as predicted, significant amounts of dsRNA can be detected for viruses with a genome consisting of positive-strand RNA, dsRNA, or DNA. Surprisingly, however, no dsRNA signals were detected for negative-strand RNA viruses. Thus, dsRNA is indeed a general feature of most virus groups, but negative-strand RNA viruses appear to be an exception to that rule.

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