Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques.
Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques.
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DOI:
10.1016/j.virol.2010.04.017
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发表时间:
2010-09-01
期刊:
影响因子:
3.7
通讯作者:
Stephens EB
中科院分区:
文献类型:
--
作者:
Schmitt K;Hill MS;Liu Z;Ruiz A;Culley N;Pinson DM;Stephens EB
The Vif protein of primate lentiviruses interacts with APOBEC3 proteins, which results in shunting of the APOBEC3-Vif complex to the proteosome for degradation. Using the simian-human immunodeficiency virus (SHIV)/macaque model, we compared the replication and pathogenicity of SHIVs that express a Vif protein in which the entire SLQ(Y/F)LA (SHIVVif5A) or HCCH (SHIVVifHCCH(−)) domains were substituted with alanine residues. Each virus was inoculated into three macaques and various viral and immunological parameters followed for six months. All macaques maintained stable circulating CD4+ T cells, developed low viral loads, maintained the engineered mutations, yielded no histological lesions, and developed immunoprecipitating antibodies early post-inoculation. Sequence analysis of nef and vpu from three lymphoid tissues revealed a high percentage of G-to-A-substitutions. Our results show that while the presence of HCCH and SLQ(Y/F)LA domains are critical in vivo, there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.
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影响因子:
3.7
作者:
Hill, M. Sarah;Ruiz, Autumn;Stephens, Edward B.
通讯作者:
Stephens, Edward B.
影响因子:
64.5
作者:
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通讯作者:
Malim, MH
影响因子:
4.8
作者:
Mehle, A;Strack, B;Gabuzda, D
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Gabuzda, D
影响因子:
4.8
作者:
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影响因子:
1.5
作者:
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通讯作者:
Stephens, Edward B.