Lim Efrem S, Emerman Michael
Department of Microbiology, University of Washington, Seattle, Washington, USA.
J Virol. 2009 Nov;83(22):11673-81. doi: 10.1128/JVI.00569-09. Epub 2009 Sep 2.
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 SIVagm 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 SIVagm 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 SIVagm. Although SIVagm Nef had an effect at low levels of AGM tetherin/BST-2, simian immunodeficiency virus SIVmus Vpu, from a virus that infects the related monkey Cercopithecus cephus, is able to antagonize even at high levels of AGM tetherin/BST-2 restriction. We propose that since the replication of SIVagm does not induce interferon production in vivo, tetherin/BST-2 is not induced, and therefore, SIVagm 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.
起源于导致人类免疫缺陷病毒1型的灵长类慢病毒谱系的Vpu辅助基因是人类束缚素/BST-2限制的拮抗剂。大多数其他灵长类慢病毒谱系，包括来自非洲绿猴（AGM）的猴免疫缺陷病毒SIVagm所代表的谱系，都不编码Vpu。虽然一些灵长类谱系编码除Vpu之外的克服束缚素/BST-2的基因产物，但我们发现SIVagm不会拮抗生理相关水平的AGM束缚素/BST-2。AGM束缚素/BST-2可由低水平的I型干扰素诱导，并能有效限制两种独立的SIVagm毒株。虽然SIVagm Nef在低水平的AGM束缚素/BST-2时具有作用，但来自感染相关猴子白顶白眉猴的病毒的猴免疫缺陷病毒SIVmus Vpu，即使在高水平的AGM束缚素/BST-2限制下也能发挥拮抗作用。我们提出，由于SIVagm的复制在体内不会诱导干扰素产生，束缚素/BST-2不会被诱导，因此，SIVagm不需要Vpu。这表明灵长类慢病毒只有在自然感染的典型过程中遇到束缚素时才会进化出诸如Vpu或Nef等束缚素拮抗剂。
