Capsid processing requirements for abrogation of Fv1 and Ref1 restriction.
Murine leukemia virus is restricted in mouse cells lines by a host factor known as Fv1 and in human cell lines by Ref1. Genetic evidence indicates that these restriction factors target the virus capsid (CA) protein. Restriction can be overcome by adding virus at a high multiplicity of infection, indicating that the restriction factors can be saturated. Cells preexposed to restricted virus will allow infection by a second virus which would normally be restricted. This phenomenon is known as abrogation; it provides us with a tool with which to study the interaction of virus with restriction factors. We tested the abilities of several Gag processing mutants to abrogate restriction. Our results show that CA must be cleaved from both p12 and nucleocapsid in order for the incoming virion to interact with the restriction factor. Endogenous expression of properly processed CA, however, failed to abrogate restriction. These results suggest that as well as being processed, CA must also be properly assembled in the form of a condensed viral core in order to interact with Fv1 and Ref1. This polymeric structure may contain restriction factor binding sites not present in monomeric CA.
Dodding
Mark P
MP
Medical Research Council, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, United Kingdom.
Bock
Michael
M
Yap
Melvyn W
MW
Stoye
Jonathan P
JP
D000818:Animals; D041702:BALB 3T3 Cells; D002213:Capsid / Q000378:metabolism*; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000502:physiology*; D015683:Gene Products, gag / Q000378:metabolism; D006801:Humans; D009052:Leukemia Virus, Murine / Q000502:physiology*; D051379:Mice; D041681:NIH 3T3 Cells; D011506:Proteins / Q000502:physiology*; D014771:Virion / Q000502:physiology
C103189:Fv1 protein, mouse; D015683:Gene Products, gag; D011506:Proteins; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase