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Purine-loading as a general immune evasive strategy

Posted by forsdyke on 30 Dec 2012 at 19:52 GMT

Zalumbide et al. (2007) attributed the immunosuppressive power of the repeat sequence in the LANA-1-encoding gene, to function at the protein level. Likewise, Kwun et al. (2007), while noting similarities between the EBNA-1 and LANA-1 repeats at the mRNA level (indicating a shift in reading frame, which we can call "Nature's experiment"), still maintained that immunosuppressive function would be at the protein level.

In a remarkable tour de force that extends their earlier studies, Tellam et al. (2012) have now formally repeated “Nature’s experiment” and changed the reading frame of the main EBNA-1 repeat so that the protein sequence of the repeat is drastically altered, while the mRNA sequence remains essentially unchanged (still heavily purine-loaded). Since this does not change the host cell’s ability to decrease immune recognition, they conclude that the cis-inhibitory effect of the repeat sequences of gammaherpesviruses operates at the nucleotide level, (see and associated "End Notes").

It has taken a long time for recognition of these RNA-level viral effects (Cristillo et al. 2001). Hopefully, the idea that this phenomenon can be part of a "general immune evasive strategy" will now be entertained more frequently. For example, the 'antisense' transcript of GC-rich HTLV-1 is heavily purine-loaded and its translation product (HBZ; Cook et al. 2012) may have some functional similarity to EBNA-1.

Cook LB, Elemans M, Rowan AG, and Asquith B. 2012. HTLV-1: persistence and pathogenesis. Virol 435: 131-140.

No competing interests declared.