TRIM5alpha mediates the postentry block to N-tropic murine leukemia viruses in human cells.
Murine leukemia viruses (MLVs) have been classified as N-tropic (N-MLV) or B-tropic (B-MLV), depending on their ability to infect particular mouse strains. The early phase of N-MLV infection is blocked in the cells of several mammalian species, including humans. This block is mediated by a dominant host factor that targets the viral capsid soon after virus entry into the cell has been achieved. A similar block to HIV-1 in rhesus monkey cells is mediated by TRIM5alpha. Here we show that human TRIM5alpha is both necessary and sufficient for the restriction of N-MLV in human cells. Rhesus monkey TRIM5alpha, which potently blocks HIV-1 infection, exhibited only modest inhibition of N-MLV infection. B-MLV was resistant to the antiviral effects of both human and rhesus monkey TRIM5alpha; susceptibility to TRIM5alpha-mediated restriction was conferred by alteration of residue 110 of the B-MLV capsid protein to the amino acid found in the N-MLV capsid. Our results demonstrate that species-specific variation in TRIM5alpha governs its ability to block infection by diverse retroviruses.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Michel J
MJ
Perron
Matthew
M
Stremlau
Byeongwoon
B
Song
Wes
W
Ulm
Richard C
RC
Mulligan
Joseph
J
Sodroski
D019943:Amino Acid Substitution; D000818:Animals; D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics / Q000494:pharmacology* / Q000502:physiology; D002460:Cell Line; D021984:Cyclophilin A / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006678:HIV / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D017053:Infection Control; D008253:Macaca mulatta; D051379:Mice; D008979:Moloney murine leukemia virus / Q000187:drug effects / Q000502:physiology*; D012190:Retroviridae / Q000187:drug effects / Q000502:physiology; D013045:Species Specificity; D014162:Transfection; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A