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

Virology
Kimberly SchmittEdward B Stephens

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 (SHIV(Vif5A)) or HCCH (SHIV(VifHCCH(-))) 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.

References

Sep 1, 1992·Virology·L Fan, K Peden
Jan 28, 1998·Journal of Virology·R C DesrosiersR P Johnson
Sep 25, 1998·Journal of Medical Primatology·S V JoagO Narayan
Jun 18, 2003·Cell·Reuben S HarrisMichael H Malim
Jul 16, 2003·Cell·Roberto MarianiNathaniel R Landau
Apr 21, 2004·Nature Structural & Molecular Biology·Qin YuNathaniel R Landau
May 14, 2004·Journal of Virology·Yong-Hui ZhengB Matija Peterlin
Oct 7, 2004·The Journal of Biological Chemistry·Qin YuNathaniel R Landau
Aug 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Kun LuoXiao-Fang Yu
Dec 17, 2005·Nature Immunology·Wayne C KoffRonald C Desrosiers
Apr 26, 2006·The Journal of Biological Chemistry·Andrew MehleDana Gabuzda
Jun 27, 2006·AIDS Research and Human Retroviruses·M Sarah HillEdward B Stephens
Sep 20, 2006·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·M Sarah HillEdward B Stephens
Apr 27, 2007·Virology·Yiliang YangLawrence Kleiman
Sep 18, 2007·Journal of Molecular Biology·Zuoxiang XiaoXiao-Fang Yu
Oct 19, 2007·Journal of Virology·Cesar A Virgen, Theodora Hatziioannou
Feb 6, 2008·Journal of Neuroimmune Pharmacology : the Official Journal of the Society on NeuroImmune Pharmacology·Joanne K MarcarioPaul D Cheney
Feb 27, 2008·The Journal of Biological Chemistry·Ying DangYong-Hui Zheng

❮ Previous
Next ❯

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.