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The phosphoprotein genes of measles viruses from subacute sclerosing panencephalitis cases encode functional as well
E L Millar1, L J Rennick2, B Weissbrich3
1Centre for Infection and Immunity, School of Medicine, Dentistry and Biomedical Sciences, The Queen's University of Belfast, Belfast, BT9 7BL Northern Ireland, UK.
Abstract:
Products expressed from the second (P/V/C) gene are important in replication and abrogating innate immune responses during acute measles virus (MV) infection. Thirteen clone sets were derived from the P/V/C genes of measles virus (MV) RNA extracted from brains of a unique collection of seven cases of subacute sclerosing panencephalitis (SSPE) caused by persistent MV in the central nervous system (CNS). Whether these functions are fully maintained when MV replicates in the CNS has not been previously determined. Co-transcriptional editing of the P mRNAs by non-template insertion of guanine (G) nucleotides, which generates mRNAs encoding the viral V protein, occurs much less frequently (9%) in the SSPE derived samples than during the acute infection (30-50%). Thus it is likely that less V protein, which is involved in combatting the innate immune response, is produced. The P genes in MV from SSPE cases were not altered by biased hypermutation but exhibited a high degree of variation within each case. Most but not all SSPE derived phospho-(P) proteins were functional in mini genome replication/transcription assays. An eight amino acid truncation of the carboxyl-terminus made the P protein non-functional while the insertion of an additional glycine residue by insertion of G nucleotides at the editing site had no effect on protein function.
Insights
Subacute sclerosing panencephalitis (SSPE) measles virus (MV) shows reduced P/V/C gene editing, likely decreasing viral V protein production and immune evasion. Most derived phospho-(P) proteins remained functional despite variations.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- The measles virus (MV) P/V/C gene products are crucial for viral replication and suppressing innate immunity during acute infections.
- Subacute sclerosing panencephalitis (SSPE) results from persistent MV infection in the central nervous system (CNS).
- The functional impact of MV replication within the CNS on P/V/C gene products and immune evasion is not well understood.
Purpose of the Study:
- To investigate the P/V/C gene products of MV in SSPE cases.
- To determine if MV functions, particularly immune evasion, are maintained during CNS persistence.
- To analyze the editing frequency and protein functionality of MV P genes derived from SSPE brains.
Main Methods:
- RNA extraction from MV-infected SSPE brain tissues.
- Cloning and sequencing of P/V/C genes from seven SSPE cases.
- Analysis of co-transcriptional editing frequency of P mRNAs.
- Functional assessment of derived phospho-(P) proteins using mini genome replication/transcription assays.
Main Results:
- MV P/V/C genes were isolated from seven SSPE cases.
- Co-transcriptional editing of P mRNAs was significantly reduced in SSPE samples (9%) compared to acute MV infection (30-50%).
- Most SSPE-derived phospho-(P) proteins were functional, though variations and a non-functional carboxyl-terminal truncation were observed. Editing site insertions did not affect function.
Conclusions:
- Reduced P mRNA editing in SSPE suggests lower V protein production, potentially impairing viral immune evasion in the CNS.
- MV P genes in SSPE exhibit high variation but retain functionality, indicating adaptability during persistent CNS infection.
- Further research is needed to fully elucidate the role of V protein in MV pathogenesis within the CNS.
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