Two surface-exposed elements of the B30.2/SPRY domain as potency determinants of N-tropic murine leukemia virus restriction by human TRIM5alpha.
Human TRIM5alpha (TRIM5alpha(hu)) potently restricts N-tropic (N-MLV), but not B-tropic, murine leukemia virus in a manner dependent upon residue 110 of the viral capsid. Rhesus monkey TRIM5alpha (TRIM5alpha(rh)) inhibits N-MLV only weakly. The study of human-monkey TRIM5alpha chimerae revealed that both the v1 and v3 variable regions of the B30.2/SPRY domain contain potency determinants for N-MLV restriction. These variable regions are predicted to be surface-exposed elements on one face of the B30.2 domain. Acidic residues in v3 complement basic residue 110 of the N-MLV capsid. The results support recognition of the retroviral capsid by the TRIM5alpha B30.2 domain.
Perron
Michel J
MJ
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, JFB 824, Boston, MA 02115, USA.
Stremlau
Matthew
M
Sodroski
Joseph
J
D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000187:drug effects / Q000276:immunology*; D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000502:physiology; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000494:pharmacology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000737:chemistry / Q000187:drug effects* / Q000472:pathogenicity; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000494:pharmacology; D012192:Retroviridae Infections / Q000503:physiopathology / Q000517:prevention & control*; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000956:Antigens, Viral; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D011506:Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases