Weiler Andrea M, Das Arpita, Akinyosoye Oluwasayo, Cui Sherry, O'Connor Shelby L, Scheef Elizabeth A, Reed Jason S, Panganiban Antonito T, Sacha Jonah B, Rakasz Eva G, Friedrich Thomas C, Maness Nicholas J
Wisconsin National Primate Research Center, Madison, Wisconsin, USA.
Division of Microbiology, Tulane National Primate Research Center, Covington, Louisiana, USA.
J Virol. 2015 Dec 4;90(4):2119-26. doi: 10.1128/JVI.01975-15. Print 2016 Feb 15.
Nef-specific CD8(+) T lymphocytes (CD8TL) are associated with control of simian immunodeficiency virus (SIV) despite extensive nef variation between and within animals. Deep viral sequencing of the immunodominant Mamu-B*017:01-restricted Nef165-173IW9 epitope revealed highly restricted evolution. A common acute escape variant, T170I, unexpectedly and uniquely degraded Nef's major histocompatibility complex class I (MHC-I) downregulatory capacity, rendering the virus more vulnerable to CD8TL targeting other epitopes. These data aid in a mechanistic understanding of Nef functions and suggest means of immunity-mediated control of lentivirus replication.
尽管动物之间以及动物体内的Nef存在广泛变异，但Nef特异性CD8(+) T淋巴细胞（CD8TL）与猿猴免疫缺陷病毒（SIV）的控制有关。对免疫显性的Mamu-B*017:01限制性Nef165-173IW9表位进行深度病毒测序，揭示了高度受限的进化。一种常见的急性逃逸变体T170I意外且独特地降低了Nef的主要组织相容性复合体I类（MHC-I）下调能力，使病毒更容易受到靶向其他表位的CD8TL的攻击。这些数据有助于从机制上理解Nef的功能，并提示免疫介导的慢病毒复制控制手段。
