A human TRIM5alpha B30.2/SPRY domain mutant gains the ability to restrict and prematurely uncoat B-tropic murine leukemia virus.
Human TRIM5alpha restricts N-tropic murine leukemia virus (N-MLV) but not B-tropic MLV (B-MLV) infection. Here we study B30.2/SPRY domain mutants of human TRIM5alpha that acquire the ability to inhibit B-MLV infection prior to reverse transcription without losing the ability to restrict N-MLV infection. Remarkably, these mutants gain the ability to decrease the amount of particulate B-MLV capsids in the cytosol of infected cells. In addition, these mutants gain the ability to restrict SIV(mac) and HIV-2 infection. B-MLV and SIV(mac) infections were blocked by the mutant TRIM5alpha proteins prior to reverse transcription. Thus, the range of retroviruses restricted by human TRIM5alpha can be increased by changes in the B30.2/SPRY domain, which also result in the ability to cause premature uncoating of the restricted retroviral capsid.
Diaz-Griffero
Felipe
F
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Department of Pathology, Division of AIDS, Harvard Medical School, Boston, MA 02115, USA.
Perron
Michel
M
McGee-Estrada
Kathleen
K
Hanna
Robert
R
Maillard
Pierre V
PV
Trono
Didier
D
Sodroski
Joseph
J
D000090103:Antiviral Restriction Factors; D002213:Capsid / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D003593:Cytoplasm / Q000821:virology; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000032:analysis / Q000235:genetics; D015498:HIV-2 / Q000276:immunology; D006801:Humans; D009052:Leukemia Virus, Murine / Q000276:immunology* / Q000502:physiology; D020125:Mutation, Missense; D017434:Protein Structure, Tertiary; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D000070584:Tripartite Motif Proteins; D049452:Green Fluorescent Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases