Human bocavirus (HBoV) was first identified in 2005. HBoV1 infection leads to various clinical manifestations such as pneumonia, bronchiolitis and acute otitis media, which can be life-threatening. The capsid mRNA transcripts of HBoV1 can be generated by alternative splicing from the mRNA precursor transcribed from the P5 promoter. However, the detailed mechanism that regulates the alternative translation of capsid proteins is still not understood.

In the present study, the research group led by Prof. GUAN Wuxiang in Wuhan Institute of Virology of Chinese Academy of Sciences found that the tricistronic capsid mRNA transcript encoded the VP1, VP2 and VP3 proteins both in vivo and in vitro. The 5’UTRs of the capsid mRNAs regulated not only the abundance of RNA transcripts, but also the expression of capsid proteins.

The upstream ATGs (uATGs) in exon 4 of the 5’UTR modulated capsid expression via a leaky scan mechanism and affected progeny virus production. Mutated uATGs in exon 4 before capsid translation start site altered the viral RNA abundance as well as mRNA processing, indicating that the 5’UTR plays an important role in the viral life cycle.

Their study showed that the 5’UTR not only modulated mRNA abundance but also regulated capsid expression. Two uATGs that were upstream of the capsid translation initiation site in the 5’UTR were found to affect viral capsid mRNA polyadenylation, alternative translation and progeny virus production.

The results reveal that uATGs play an important role in the viral life cycle and represent a new layer to regulate HBoV1 RNA processing, which could be a target for gene therapy, which have been published in Journal of Virology entitled "5’UTR of human bocavirus capsid transcripts regulates its mRNA biogenesis and alternative translation".

The study was supported by Ministry of Science and Technology of China, Chinese Academy of Sciences and Open Research Fund Program of CAS Key Laboratory of Special Pathogens and Biosafety, Chinese Academy of Sciences.

5’UTR regulated HBoV1 capsid mRNA abundance and protein translation. Image by GUAN Wuxiang

Contact:

GUAN Wuxiang

E-mail: guanwx@wh.iov.cn

Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China (http://english.whiov.cas.cn/)