Project Details
Description
Schmallenberg virus (SBV) is an emerging arbovirus. After its identification
in 2011, SBV spread rapidly in several European countries. Although it is
rather clinically innocuous in adult ruminant, SBV causes severe
malformations in newborn. Genetic analysis revealed that SBV belongs to
the genus Orthobunyavirus within the Bunyaviridae family and is related to
the Simbu serogroup. Its tripartite genome is composed of negative sense
RNA segments (S, M and L), encoding 6 proteins in total. These genomic
segments, consist of a coding region flanked by nontranslated regions (5’
and 3’ NTR) that are transcribed into complementary RNAs and mRNAs.
Through SBV mRNA termini characterization, we found that viral mRNAs
acquired 5’cap after cap-snatching from host mRNAs but lack poly(A) tail at
their 3’end. Since poly(A) tail is crucial for the mRNA stability and
translation, mRNA devoid of poly(A) tail must adopt alternative strategies
that will be investigated in this proposal. In silico analyses revealed a
conserved hairpin and a putative transcription termination signal both
localized in the 3’NTR of the SBV S segment. Their localization and their
conservation within the Simbu serogroup suggest that these two signals are
crucial determinants for viral replication. Different biological questions will
be investigated in this proposal: (i) What are the viral sequences triggering
termination of mRNA transcription and activation of viral RNA translation?
(ii) What are the protein networks associated with transcription
initiation/termination and poly(A)-independent translation during SBV
replication? (iii) Are the candidate proteins identified in the different
RNA/protein complexes functionally relevant in the context of SBV
replication? These questions will be addressed by using mainly reporter
assays and RNA-affinity purifications follow by mass spectrometry. Thus,
this proposal aims for better understanding Bunyavirus replication
mechanisms.
in 2011, SBV spread rapidly in several European countries. Although it is
rather clinically innocuous in adult ruminant, SBV causes severe
malformations in newborn. Genetic analysis revealed that SBV belongs to
the genus Orthobunyavirus within the Bunyaviridae family and is related to
the Simbu serogroup. Its tripartite genome is composed of negative sense
RNA segments (S, M and L), encoding 6 proteins in total. These genomic
segments, consist of a coding region flanked by nontranslated regions (5’
and 3’ NTR) that are transcribed into complementary RNAs and mRNAs.
Through SBV mRNA termini characterization, we found that viral mRNAs
acquired 5’cap after cap-snatching from host mRNAs but lack poly(A) tail at
their 3’end. Since poly(A) tail is crucial for the mRNA stability and
translation, mRNA devoid of poly(A) tail must adopt alternative strategies
that will be investigated in this proposal. In silico analyses revealed a
conserved hairpin and a putative transcription termination signal both
localized in the 3’NTR of the SBV S segment. Their localization and their
conservation within the Simbu serogroup suggest that these two signals are
crucial determinants for viral replication. Different biological questions will
be investigated in this proposal: (i) What are the viral sequences triggering
termination of mRNA transcription and activation of viral RNA translation?
(ii) What are the protein networks associated with transcription
initiation/termination and poly(A)-independent translation during SBV
replication? (iii) Are the candidate proteins identified in the different
RNA/protein complexes functionally relevant in the context of SBV
replication? These questions will be addressed by using mainly reporter
assays and RNA-affinity purifications follow by mass spectrometry. Thus,
this proposal aims for better understanding Bunyavirus replication
mechanisms.
| Short title | BUTAN-Bunyavirus Translation Alternative |
|---|---|
| Status | Finished |
| Effective start/end date | 1/01/17 → 31/12/18 |
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