Comparison of the replication and persistence of simian-human immunodeficiency viruses expressing Vif proteins with mutation of the SLQYLA or HCCH domains in macaques

Abstract 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 ex...

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Bibliographic Details
Published in:Virology (New York, N.Y.) N.Y.), 2010-09, Vol.404 (2), p.187-203
Main Authors: Schmitt, Kimberly, Hill, M. Sarah, Liu, Zhenqian, Ruiz, Autumn, Culley, Nathan, Pinson, David M, Stephens, Edward B
Format: Article
Language:English
Subjects:
Alanine
Animal models
Animals
Antibodies
Antibodies, Viral
APOBEC3F
APOBEC3G
BC box
CD4 antigen
Cell Line
Gene Products, vif - genetics
Gene Products, vif - metabolism
HIV-1 - genetics
HIV-1 - physiology
Humans
Immunodeficiency
Infectious Disease
Lentivirus
Lymphocytes - virology
Lymphocytes T
Lymphoid tissue
Macaca
Macaca mulatta
Mutagenesis, Site-Directed
Mutation
Nef protein
Pathogenicity
Primates
proteasomes
Protein Structure, Tertiary
Replication
Rhesus macaques
SHIV
Simian Acquired Immunodeficiency Syndrome - virology
Simian Immunodeficiency Virus - genetics
Simian Immunodeficiency Virus - physiology
Simian-human immunodeficiency virus
Vif
Vif protein
Viral Load
Virus Replication - physiology
Zn binding motif
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Summary:Abstract 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 SLQYLA (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 6 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 SLQYLA domains are critical in vivo , there may exist APOBEC3 negative reservoirs that allow for low levels of viral replication and persistence but not disease.
ISSN:0042-6822
1096-0341
DOI:10.1016/j.virol.2010.04.017