Transcription of the influenza virus genome

Hay, Alan J.; Lomniczi, B.; Bellamy, A R; Skehel, J.J.

doi:10.1016/0042-6822(77)90179-9

Cited by 235 publications

(233 citation statements)

References 25 publications

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“…1B). These results are in agreement with previous findings that actinomycin D does not affect viral RNA replication directly and that the accumulation of viral replication products is dependent on viral protein expression (1,12,13). Preexpression of NP and wild-type catalytically active viral RdRp resulted not only in cRNA accumulation but also in genomic replication (linear accumulation of vRNA) (Fig.…”

supporting

confidence: 83%

“…In contrast, cRNAs are stabilized by the association of viral factors, i.e., the viral RdRp and NP, which together form a cRNP structure similar to that of vRNPs. During infection, viral mRNAs can be detected initially, while cRNAs become detectable only after the onset of viral protein synthesis (12). This has been interpreted to mean that a switch of polymerase function from a transcriptase to a replicase is required for cRNA synthesis, and various models have been proposed that implicate viral and host factors, as well as small viral RNAs (svRNAs), in the switching (reviewed in reference 17).…”

mentioning

confidence: 99%

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Stabilization of Influenza Virus Replication Intermediates Is Dependent on the RNA-Binding but Not the Homo-Oligomerization Activity of the Viral Nucleoprotein

Vreede

Shaw

et al. 2011

J Virol

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The influenza virus nucleoprotein (NP) is believed to play a central role in directing a switch from RNA genome transcription to replication by the viral RNA polymerase. However, this role has recently been disputed with the proposal of alternative regulatory mechanisms. It has been suggested that the expression of viral polymerase and NP allows genome replication by stabilization of cRNA replication intermediates and complementary ribonucleoprotein (cRNP) assembly. Here, we demonstrate that the RNA-binding activity of NP is necessary for stabilization of cRNA, whereas, surprisingly, homo-oligomerization of NP is not essential. However, both RNA binding and homo-oligomerization activities are essential for genome replication.Influenza virus, a member of the Orthomyxoviridae family, contains a segmented, negative-sense, single-stranded RNA (ssRNA) genome. Each viral RNA (vRNA) segment is bound by the viral RNA-dependent RNA polymerase (RdRp) and nucleoprotein (NP) to form viral ribonucleoprotein (vRNP) complexes. Within the vRNP, the RdRp binds to the corkscrew structure formed by the partially complementary conserved 5Ј and 3Ј ends of the vRNA representing the vRNA promoter. The rest of the vRNA interacts with multiple copies of NP, each molecule covering approximately 24 nucleotides (reviewed in reference 17). NP binds ssRNA with high affinity but little or no sequence specificity (2, 9, 22) and has been shown to homo-oligomerize and interact with the PB1 and PB2 subunits of the viral RdRp (4,8,14,15,23). Although cryoelectron microscopy reconstitution images of a mini-RNP containing nine NP molecules have been obtained (6), a detailed high-resolution structure of the vRNP is still lacking.During the viral life cycle, the vRNA is transcribed into mRNA and replicated through a cRNA intermediate into more copies of vRNA by the viral RdRp (reviewed in references 10, 17, and 18). Viral mRNAs associate with cellular factors normally associating with host mRNAs, e.g., nuclear and cytoplasmic cap-binding proteins, leading to the stabilization of viral mRNAs and their processing, nuclear export, and translation (3,16,21). In contrast, cRNAs are stabilized by the association of viral factors, i.e., the viral RdRp and NP, which together form a cRNP structure similar to that of vRNPs. During infection, viral mRNAs can be detected initially, while cRNAs become detectable only after the onset of viral protein synthesis (12). This has been interpreted to mean that a switch of polymerase function from a transcriptase to a replicase is required for cRNA synthesis, and various models have been proposed that implicate viral and host factors, as well as small viral RNAs (svRNAs), in the switching (reviewed in reference 17). However, an alternative interpretation is that both mRNA and cRNA are synthesized from early on in a stochastic manner but cRNA is degraded by host nucleases until sufficient amounts of viral RdRp and NP accumulate to stabilize it (20). In agreement with this interpretation, the overexpression of catalytically...

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supporting

confidence: 83%

mentioning

confidence: 99%

Stabilization of Influenza Virus Replication Intermediates Is Dependent on the RNA-Binding but Not the Homo-Oligomerization Activity of the Viral Nucleoprotein

Vreede

Shaw

et al. 2011

J Virol

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“…Upon entry into the nucleus, parental RNPs are first transcribed (primary transcription) and the synthesis of new virus proteins is necessary to proceed to RNA replication. 9 The transcription process is initiated by cap-snatching, i.e., the cleavage of 5'-capped RNA fragments from host premRNAs. 10 Subsequently, these are used as primers to copy the template and the mRNAs are finally polyadenylated.…”

Section: The Influenza Rna Synthesis Machinementioning

confidence: 99%

The influenza virus RNA synthesis machine

et al. 2011

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“…Both the MS1 and NS2 mRNAs are transcribed from genome segment 8 of influenza virus (4,5), and since the NS1 mDRNA is an almost complete transcript of the vRNA (8), it follows that the sequences of the NS2 mRNA must also be present on the MS1 MRNA but in a form which precludes their expression. We used reverse transcriptase to synthesise complementary DNA copies of mRNAs from FPV-infected cells.…”

Section: Discussionmentioning

confidence: 99%

“…These genes are expressed independently in the infected cell through separate species of polyadenylated mRNA. The mRNA encoding NS1 is synthesised early in infection (8,9), and represents virtually a complete transcript of vRNA segment 8 (10); the NS1 mRNA must therefore also contain the coding sequences for NS2. However the NS2 polypeptide is ©) IRL Press Umited, 1 Falconberg Court, London W1V 5FG, U.K.…”

Section: Introductionmentioning

confidence: 99%

Relationship between the messenger RNAs transcribed from two overlapping genes of influenza virus

Inglis¹,

Gething²,

Brown³

1980

Nucl Acids Res

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The relationship of the mRNAs encoding the NS1 and NS2 polypeptides of influenza virus has been investigated through synthesis and characterisation of complementary DNA copies of the mRNAs. Previous work had shown that both mRNAs are encoded by virion RNA segment 8, and that the sequences comprising the smaller of the two mRNAs (the NS2 mRNA) were also present on the NS1 mRNA. Our results indicate that the mRNA encoding the NS2 polypeptide of the avian influenza, fowl plague virus, is approximately 400 ntds long, and that its sequences correspond largely with the 3'-terminal region of the NSl mRNA.

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Transcription of the influenza virus genome

Cited by 235 publications

References 25 publications

Stabilization of Influenza Virus Replication Intermediates Is Dependent on the RNA-Binding but Not the Homo-Oligomerization Activity of the Viral Nucleoprotein

Stabilization of Influenza Virus Replication Intermediates Is Dependent on the RNA-Binding but Not the Homo-Oligomerization Activity of the Viral Nucleoprotein

The influenza virus RNA synthesis machine

Relationship between the messenger RNAs transcribed from two overlapping genes of influenza virus

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