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Translation of Giardiavirus (GLV) mRNA is initiated at an internal ribosome entry site (IRES) in the viral transcript. The IRES localizes to a downstream portion of 5′ untranslated region (UTR) and a part of the early downstream coding region of the transcript. Recent studies indicated that the IRES does not require a pre-initiation complex to initiate translation but may directly recruit the small ribosome subunit with the help of a number of  trans -activating protein factors. A La autoantigen homologue in the viral host  Giardia lamblia , GlLa, was proposed as one of the potential  trans -activating factors based on its specific binding to GLV-IRES  in vitro . In this study, we further elucidated the functional role of GlLa in GLV-IRES mediated translation in  Giardia  by knocking down GlLa with antisense morpholino oligo, which resulted in a reduction of GLV-IRES activity by 40%. An over-expression of GlLa in  Giardia  moderately stimulated GLV-IRES activity by 20%. A yeast inhibitory RNA (IRNA), known to bind mammalian and yeast La autoantigen and inhibit Poliovirus and Hepatitis C virus IRES activities  in vitro  and  in vivo , was also found to bind to GlLa protein  in vitro  and inhibited GLV-IRES function  in vivo . The C-terminal domain of La autoantigen interferes with the dimerization of La and inhibits its function. An over-expression of the C-terminal domain (200–348aa) of GlLa in  Giardia  showed a dominant-negative effect on GLV-IRES activity, suggesting a potential inhibition of GlLa dimerization. HA tagged GlLa protein was detected mainly in the cytoplasm of  Giardia , thus supporting a primary role of GlLa in translation initiation in Giardiavirus.

A La Autoantigen Homologue Is Required for the Internal Ribosome Entry Site Mediated Translation of Giardiavirus