Δ382, a milder Variant of SARS2 dropped an entire Open Reading Frame (ORF8 was designed to suppress T-cells)

submitted by infocom6502 from medium.com

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[–]infocom6502[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (2 children)

the ∆382 variant has a 382-nucleotide deletion that removed the gene that codes for the ORF8 protein. What does the ORF8 protein do?

....

the ORF8 protein inhibits the MHC class I molecules that are required for activating cytotoxic T-cells that kill infected cells. Basically, the ORF8 protein helps SARS-CoV-2 to avoid detection and killing by T-cells.

(Normally T-cells will kill cells where clusters of Viruses are incubating---with the mechanism in ORF8, this is somewhat inhibited.)

[–]infocom6502[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (1 child)

Update: It seems the ORF8 is almost the same for two related coronaviruses. The ratg13, as well as ZC45 (SARS like bat CoV, also known as "Bat CoV SL-CoV ZC45" which was sampled in Feb 2017.

See figure 4 in this study:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812859/

[–]infocom6502[S] 1 insightful - 1 fun1 insightful - 0 fun2 insightful - 1 fun -  (0 children)

A Pangolin CoV also has a somewhat similar ORF8, however without the insertion (see below) that's found in the three CoV's above. The amino acid sequence for the insertion is:

IELCVDEVGSKSPICYI

blastp gives a few matches, some partial matching fragments to organisms like soybeans, house mouse, and even zebrafish. Some more interesting matches are:

Select seq ref|NP_991180.1| cilia- and flagella-associated protein 206 [Danio rerio] Danio rerio 23.5 38.6 47% 65 100.00% 624 NP_991180.1

Ig-like domain-containing protein Shewanella oneidensis Shewanella oneidensis 23.5 23.5 35% 65 100.00% 826 WP_011073787.1

RNA helicase, putative [Leishmania donovani] Leishmania donovani 23.5 23.5 35% 65 100.00% 1234 XP_003858688.1

hypothetical protein, conserved [Leishmania donovani] Leishmania donovani 23.5 39.0 52% 65 100.00% 1268 XP_003859050.1

hypothetical protein DDB_G0276125 Dictyostelium discoideum AX4 [Slime mold] AX4 23.5 39.0 58% 65 88.89% 1338 XP_643252.1

Regarding the Leishmania, the actions of this pathogen sound similar to the new Sars:

[Leishmania donovani] are able to survive and replicate inside these primary immune systems. The parasites manipulate the cell signalling pathway of the macrophages, such as down-regulating of Jak/stat signalling, NO and TNF-α production, and also by blocking the NF-κB-dependent pathway. There are two major mechanisms of immune evasion such as induction of immune suppressive IL-10 responses....