Synthesis of antigenomic RNA of human respiratory syncytial virus

Stable Identifier
R-HSA-9834736
Type
Reaction [omitted]
Species
Homo sapiens
Related Species
Human respiratory syncytial virus A
Compartment
cytosol
ReviewStatus
5/5
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Synthesis of antigenomic RNA of human respiratory syncytial virus
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After the primary round of transcription, accumulation of the M2-2 protein leads to a rearrangement of the ribonucleocapsid of the human respiratory syncytial virus (RSV), likely through direct interaction of M2-2 with the ribonucleocapid (Blanchard et al. 2020). M2-2 promotes the switch from transcription of viral genes to replication of the viral genome for virion assembly (Bermingham et and Collins 1999) through M2-2-mediated structural rearrangement of the nucleocapsid (Blanchard et al. 2020). M2-2 does not interfere with the secondary round of transcription. The mechanism of M2-2 action has not been elucidated (Blanchard et al. 2020). The level of M2-2 expression has to be tightly regulated as overexpression of M2-2 inhibits replication (Cheng et al. 2005). RSV lacking M2-2 grows less efficiently, with reduced production of genomic RNA and increased production of viral proteins (Bermingham and Collins 1999).

The replication of the RSV negative sense single stranded RNA genome proceeds through synthesis of a positive sense RNA genome intermediate, also known as antigenomic RNA. Antigenomic RNA is produced at very low levels (Blanchard et al. 2020).

A cis element in the first 11 nucleotides of the 44 nucleotide-long leader region at the 3' terminus of the negative sense RSV genome is needed for the initiation of the replication. Nucleotides 16-34 of the leader region are needed for production of the full-length positive-sense RSV antigenome and encapsidation of the antigenome, which happens concurrently with replication (McGivern et al. 2005).

M2-1 acts as a transcription processivity factor and its function depends on the Cys3-His1 motif consisting of 3 conserved cysteine residues C7, C15, and C21, and one conserved histidine residue, H25 (Tang et al. 2001).

The RNA-dependent RNA polymerase (RdRP) complex of RSV starts the replication of viral RNA by incorporating the correct first nucleotide (ATP) independently of the template allowing highly accurate initiation of replication (Noton et al. 2010).

Replication of RSV is positively regulated by the heat shock protein, HSP90, which has been shown to bind directly to the viral L polymerase (Geller et al. 2013; Munday et al. 2015).
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Catalyst Activity

RNA-dependent RNA polymerase activity of RdRP:p-M2-1:hRSV A nucleocapsid [cytosol]

Physical Entity
RdRP:p-M2-1:hRSV A nucleocapsid [cytosol] (Human respiratory syncytial virus A)
Activity
RNA-dependent RNA polymerase activity (GO:0003968)
This event is regulated
Positively by
Regulator
HSP90 dimer [cytosol] (Homo sapiens)
Active Unit
HSP90 dimer [cytosol]
Requirements
Disease
Authored
Orlic-Milacic, M  (2023-05-10)
Reviewed
Bergeron, HC  (2023-11-03)
Created
Orlic-Milacic, M  (2023-05-10)
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