After a cup of coffee, it occurs to me that more likely than a fused polypeptide is that the genome annotators missed a splice site, and that these are two distinct proteins. (As I’m sure you know, adenoviruses are splicing nightmares.)

As far as I can tell from the literature, no one has really looked at E3gp19k function in most adenovirus subgroups other than subgroup C. (I won’t swear there’s nothing in the literature, though. Searching for “A” or “F” in publemd doesn’t really help narrow the field much.) I have a student who is running through representatives of the various subgroups (fairly superficially, though) and we’ll see if we can figure out something.

I did find the AdF CR1 as weakly homologous to gp19k. CR1 is supposedly a complement receptor, and other ad subgroups have CR1s as well. At the time I tried comparing the putative AdF CR1 to other CR1s and to gp19ks and at the time I convinced myself that it was a more plausible CR1 than gp19k

I have observed something similar, but after having a closer look I think that these similarities are based on different parts of the sequence. The AdF CR1 proteins have two domains, a V-set like Ig domain (which has similarity to CR1 proteins from other adenovirus classes but not to gp19k) and a 2nd extracellular part that is related to gp19k but not to other CR1 proteins. I would interpret this as a kind of fusion of CR1 and gp19k into one protein for the AdF viruses. By the way, are you sure that the CR1 proteins are supposedly complement receptors? From reading the database entries and a little literature, the “CR1″ probably just means “conserved region 1″.

Interestingly, the Ig domain of the adenovirus CR1s is related to several CMV genes that are involved in cell tropism – maybe they have a similar role in the adenoviruses. It would seem a strange idea to have a cell tropism domain and an MHC evasion domain on the same polypeptide. Without having any real evidence, I would guess that the gp19k proteins mainly do something different from messing with MHCs.

I did find the AdF CR1 as weakly homologous to gp19k. CR1 is supposedly a complement receptor, and other ad subgroups have CR1s as well. At the time I tried comparing the putative AdF CR1 to other CR1s and to gp19ks and at the time I convinced myself that it was a more plausible CR1 than gp19k; I didn’t keep notes on how I did the comparisons or what the similarities were, and quickly re-running those comparisons I’m not so convinced any more; the similarity to other CR1 is not great either. I don’t know the basis on which the AdF gene was termed CR1 — whether there was a functional basis for it. In any case, it’s certainly way divergent.

To clarify a point, I think it’s well established that immune evasion in general is important to viruses; I’m restricting my question here to the specific subset of immune evasion that supposedly reduces MHC class I-restricted recognition. There are some very impressive experiments showing that some immune evasion genes, especially cytokine inhibitors and decoys, are very important for virus pathogenesis, and that’s true for a wide range of viruses.

In your post, you raise the interesting question if some adenoviruses can do without a gp19k or if it is too divergent to be recognized. I have briefly looked into that issue using our sequence comparison methods, which are more sensitive than BLAST. I got mixed results: there are very divergent gp19k versions in class F adenoviruses (human ADV41 and ADV52, simian ADV1) but I was not able to find anything in murine adenoviruses. The class-F gp19k homologs (typcially called RL2 or CR1-beta1) are not only divergent but also have an additional Ig-like domain at the N-terminus. The similarity is restricted to the ectodomain of gp19k, which probably also resembles an Ig-fold.

This does not answer the question if immune evasion is generally important for viruses. I would guess that it is, but probably using a variety of mechanisms, not all of which can be recapitulated in vitro.