Simian Immunodeficiency Virus SIV agm from African Green Monkeys Does Not Antagonize Endogenous Levels of African Green Monkey Tetherin/BST-2

Abstract

ABSTRACT The Vpu accessory gene that originated in the primate lentiviral lineage leading to human immunodeficiency virus type 1 is an antagonist of human tetherin/BST-2 restriction. Most other primate lentivirus lineages, including the lineage represented by simian immunodeficiency virus SIV agm from African green monkeys (AGMs), do not encode Vpu. While some primate lineages encode gene products other than Vpu that overcome tetherin/BST-2, we find that SIV agm does not antagonize physiologically relevant levels of AGM tetherin/BST-2. AGM tetherin/BST-2 can be induced by low levels of type I interferon and can potently restrict two independent strains of SIV agm . Although SIV agm Nef had an effect at low levels of AGM tetherin/BST-2, simian immunodeficiency virus SIV mus Vpu, from a virus that infects the related monkey Cercopithecus c ephus , is able to antagonize even at high levels of AGM tetherin/BST-2 restriction. We propose that since the replication of SIV agm does not induce interferon production in vivo, tetherin/BST-2 is not induced, and therefore, SIV agm does not need Vpu. This suggests that primate lentiviruses evolve tetherin antagonists such as Vpu or Nef only if they encounter tetherin during the typical course of natural infection.