Ancient Origin of a Deletion in Human BST2/Tetherin that Confers Protection Against Viral Zoonoses

作者：Sauter Daniel; Vogl Michael; Kirchhoff Frank^*

来源：Human Mutation, 2011, 32(11): 1243-1245.

DOI：10.1002/humu.21571

• host restriction factors
• viral antagonists
• posi-tive selection
• BST2
• tetherin

Bone marrow stromal antigen 2 (BST2)/Tetherin is an antiviral factor that blocks the release of enveloped virions from infected cells. Recent data suggest that efficient BST2 antagonism was a prerequisite for the global spread of HIV/AIDS. Most simian immunodeficiency viruses (SIVs), including the direct precursors of HIV, use their Nef protein to antagonize BST2 of their respective host species. Human BST2, however, contains a five amino acid deletion in its cytoplasmic domain that confers resistance to Nef. Thus, this antiviral factor constitutes a major barrier to effective zoonotic transmissions of SIVs to humans. Here, we show that this protective deletion has already been present in Neanderthal and Denisovan BST2 and thus evolved at least 800,000 years ago. This ancient origin helps to explain why effectively spreading zoonotic transmissions of SIVs to humans have been rare, although SIVs are widespread in African non-human primates and humans must have been exposed to these viruses many times. Hum Mutat 32: 1243-1245, 2011.

• 出版日期2011-11