Recombinant host cell with heterologous nucleic acids encoding SHREK proteins
Recombinant viruses include one or more SHREK proteins and are thereby rendered non-infective and can be safely used in vaccines, e.g. to treat or prevent infections and to eliminate e.g. latent virus reservoirs.
1. A recombinant host cell comprising
one or more vectors comprising heterologous nucleic acid sequences encoding
one or more Surface-Hinged, Rigidly-Extended Killer (SHREK) proteins selected from the group consisting of CD43, TMEM123, CD164, Tim-1, CD34, PODXL2, CD45, CD44, Madcam1, glycam1, Cd68, CD148, CX3CL1, CD107a, CD99, and CD7, and
a viral genome selected from the group consisting of coronavirus, a lentivirus, a hepadnavirus, and an influenza virus.
2. The host cell of claim 1 , wherein the host cell is a mammalian cell.
3. The recombinant host cell of claim 1 wherein the viral genome is a lentivirus.
4. The recombinant host cell of claim 3 wherein the lentivirus is HIV-1.
5. The recombinant host cell of claim 1 wherein the viral genome is a coronavirus.
6. The recombinant host cell of claim 5 wherein the coronavirus is SARS-CoV-2.
7. The recombinant host cell of claim 1 wherein the viral genome is a hepadnavirus.
8. The recombinant host cell of claim 7 wherein the hepadnavirus is HBV.
9. A method of producing virions, comprising
I) introducing into a host cell
a nucleic acid sequence encoding at least one Surface-Hinged, Rigidly-Extended Killer (SHREK) protein, wherein the at least one SHREK protein is selected from the group consisting of CD43, TMEM123, CD164, Tim-1, CD34, PODXL2, CD45, CD44, Madcam1, glycam1, Cd68, CD148, CX3CL1, CD107a, CD99, and CD7, and
one or more nucleic acid sequences encoding a viral genome;
II) culturing the host cell in a culture medium under conditions that permit
i) over-expression of the SHREK protein from the nucleic acid sequence and over-expression of viral proteins and viral nucleic acids from the one or more nucleic acid sequences, and
ii) assembly of the viral proteins and viral nucleic acids into virions comprising the SHREK protein; and
III) recovering the virions from the culture medium.
10. The method of claim 9 wherein the host cell is a mammalian cell.
11. The method of claim 9 wherein the viral genome is selected from the group consisting of coronavirus, a lentivirus, a hepadnavirus, and an influenza virus.
12. The method of claim 11 wherein the viral genome is a lentivirus.
13. The method of claim 12 wherein the lentivirus is HIV-1.