The cytoplasmic body component TRIM5alpha restricts HIV-1 infection in Old World monkeys.
Host cell barriers to the early phase of immunodeficiency virus replication explain the current distribution of these viruses among human and non-human primate species. Human immunodeficiency virus type 1 (HIV-1), the cause of acquired immunodeficiency syndrome (AIDS) in humans, efficiently enters the cells of Old World monkeys but encounters a block before reverse transcription. This species-specific restriction acts on the incoming HIV-1 capsid and is mediated by a dominant repressive factor. Here we identify TRIM5alpha, a component of cytoplasmic bodies, as the blocking factor. HIV-1 infection is restricted more efficiently by rhesus monkey TRIM5alpha than by human TRIM5alpha. The simian immunodeficiency virus, which naturally infects Old World monkeys, is less susceptible to the TRIM5alpha-mediated block than is HIV-1, and this difference in susceptibility is due to the viral capsid. The early block to HIV-1 infection in monkey cells is relieved by interference with TRIM5alpha expression. Our studies identify TRIM5alpha as a species-specific mediator of innate cellular resistance to HIV-1 and reveal host cell components that modulate the uncoating of a retroviral capsid.
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA.
Matthew
M
Stremlau
Christopher M
CM
Owens
Michel J
MJ
Perron
Michael
M
Kiessling
Patrick
P
Autissier
Joseph
J
Sodroski
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D022083:Cytoplasmic Structures / Q000737:chemistry* / Q000378:metabolism; D004198:Disease Susceptibility; D014644:Genetic Variation / Q000235:genetics; D015658:HIV Infections / Q000378:metabolism* / Q000662:veterinary / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015302:Simian Immunodeficiency Virus / Q000502:physiology; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication
D020033:Protein Isoforms; D011506:Proteins; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases