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Request for clarification/insight on 2019-nCoV recombination question.
#1
Greetings,

I hope this is the correct sub-forum!

There has been some controversy as to whether the four 3-6 amino acid residue sequence additions found in the spike protein of 2019-nCoV could be of potential significance. Some had argued all four matching samples of HIV-1 was of interest, while others have suggested the comparatively short sequences and presence of sequence gaps potentially matching hundreds of other candidates (though not necessarily all four as with HIV-1), made it less helpful for identifying a possible intermediate carrier.

The main study which originally identified these additions has been hotly debated in its wording and conclusions and is currently withdrawn for review by its authors, however the presence of these sequences and their persistence has not been challenged: https://www.biorxiv.org/content/10.1101/...1.full.pdf

Taking these findings in a different direction, I wanted to clarify whether it would be theoretically possible for these four potential HIV-1 matches to inherit larger HIV-1 spike components from a co-infection of HIV-1 and 2019-nCoV within a single human host cell via recombination, using these fragments as a translation template?

I imagine it would depend on modeling whether the location and spacing of these four template markers could potentially match an equivalent range in a candidate HIV-1 sequence that, if transferred by recombination, could constitute any significant change in functional capacity of the 2019-nCoV receptor site (where these 4 markers are located).

Obviously the main concern being whether the ability to infect HIV-1 target receptors could be inherited through such a hypothetical transfer.

Please bear in mine I have no real world experience in molecular biology or genetics as my background is Computer Science and IT.

Are there any know analogs for such a recombination naturally of material from one viral source to another with large sequence gaps? If so I was mainly interested in probability for and against such a scenario occurring given the present expression of these four candidate sequence markers and their locations.

As a possible mechanism for co-infection, I considered a hypothetical scenario where an individual previously infected with HIV-1 subsequently contracted 2019-nCoV. During the later disease progression, the patient develops hemoptysis.

Could there be a possible mechanism whereby HIV-1 infected blood in the airways could transfer HIV-1 into a 2019-nCoV infected cell?

Is there any other mechanism whereby a person infected with both diseases might see them co-infect the same cell and transfer material, despite the fact they target different receptors, possibly through some Gag particle assembly mechanism or other known process?

While many have been quick to dismiss the likelihood of 2019-nCoV inheriting parts of HIV-1, they also point out it is not altogether impossible. This is the part I am unclear on. They largely base their conclusions on the assumption of a scenario where the material is inherited from an intermediary animal, while indicating more research is needed to determine if that is indeed the case, as such a candidate animal has yet to be found.

It seems remarkable that these four additions or 'inserts' (debate exists on the classification) appear to be conserved in all available 2019-nCoV sequences. It COULD tend to reinforce an artificial origin, in a hypothetical scenario where such recombination was theoretically possible yet necessitated long term stability of the template to facilitate what may require very rare circumstances (the probability equation) and many random recombinations to achieve.

Admittedly the scenario seems unlikely. It also may be that I am simply ignorant to the reasons why both virus entering the same cell and recombining in such a way is not actually possible. However, I felt compelled to ask.

Best regards,

-James
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#2
So in researching this further on my own I came upon the following papers which have helped to clarify this for me somewhat:

This paper talks about how the likelihood of recombination of non-homologous RNA depends on sequence similarity of the inserts (and probably also their location): https://www.ncbi.nlm.nih.gov/pmc/article...3-0383.pdf

This one addresses the findings of the disputed paper linked in my original post, specifically noting that "all four insertions are located outside the Receptor Binding Domain (RBD) of spike" which, combined with the exceptionally small sequences of the inserts, seems to suggest it would be extremely unlikely for recombination of HIV-1 components to be inherited by 2019-nCoV in a way that would modify its receptor binding behavior: https://arxiv.org/ftp/arxiv/papers/2002/2002.03173.pdf

(There is also some knowledge about these sort of small inserts being mobile in the larger sequence, and it doesn't perform any in-depth analysis of potential convergence in the receptor region relative to an HIV-1 analog as to explore potential recombination scenarios, so there is still uncertainty here, at least for me.)

Finally this last link is to the above author's bioinformatics lab page on 2019-nCoV where you can explore the various structures of the virus, their known or predicted function (based on database matches of highly homologous analogs), with sequence strings and interactive 3D models: https://zhanglab.ccmb.med.umich.edu/C-I-...2019-nCov/
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