Human Immunodeficiency Virus Type‐1 Accessory Protein Vpr: A Causative Agent of the AIDS‐Related Insulin Resistance/Lipodystrophy Syndrome?

@article{Kino2004HumanIV,
  title={Human Immunodeficiency Virus Type‐1 Accessory Protein Vpr: A Causative Agent of the AIDS‐Related Insulin Resistance/Lipodystrophy Syndrome?},
  author={Tomoshige Kino and George P. Chrousos},
  journal={Annals of the New York Academy of Sciences},
  year={2004},
  volume={1024}
}
  • T. Kino, G. Chrousos
  • Published 1 June 2004
  • Biology, Medicine
  • Annals of the New York Academy of Sciences
Abstract: Recent advances in the development of three different types of antiviral drugs, the nucleotide and non‐nucleotide analogues acting as reverse transcriptase inhibitors (NRTIs) and the nonpeptidic viral protease inhibitors (PI), and their introduction in the management of patients with AIDS, either alone or in combination, have dramatically improved the clinical course of the disease and prolonged life expectancy in patients with AIDS. The increase in life expectancy in association with… 
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References

SHOWING 1-10 OF 103 REFERENCES
AIDS-related lipodystrophy/insulin resistance syndrome.
TLDR
The current understanding of the pathogenesis of this severe AIDS-associated lipodystrophy/insulin resistance syndrome is reviewed, which appears to be multi-factorial and may induce the pathologic changes of this syndrome or increase the vulnerability of patients to the adverse effect of the therapeutic compounds.
Mitochondria in the pathogenesis of lipodystrophy induced by anti-HIV antiretroviral drugs: actors or bystanders?
TLDR
Data concerning the role of mitochondria in the pathogenesis of lipodystrophy is reviewed, and a unifying hypothesis involving either direct or indirect effects of the drugs employed during HAART is advanced.
The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle
TLDR
It is shown that infected cells are unable to progress normally through the cell cycle and became arrested in the G2 + M phase and the HIV-1 vpr gene product is identified as being both necessary and sufficient for eliciting this cell cycle arrest.
Metabolic Disorders Among HIV‐Infected Patients Treated With Protease Inhibitors: A Review
  • N. Graham
  • Medicine, Biology
    Journal of acquired immune deficiency syndromes
  • 2000
TLDR
Prospective controlled studies are needed to define whether protease inhibitors currently under development are less prone to produce the lipodystrophy syndrome, and whether complete normalization of fast‐wasted body regions is possible.
Human immunodeficiency virus type 1 vpr protein transactivation function: mechanism and identification of domains involved.
TLDR
The mutagenic analysis indicates that the transactivation mediated by Vpr is not dependent on the ability of the protein to localize in the nucleus or to be packaged in the virions.
The immunopathogenesis of human immunodeficiency virus infection.
TLDR
The human immunodeficiency virus is probably the most intensively studied virus in the history of biomedical research, and many of the pathogenic mechanisms associated with HIV infection that lead to clinical disease have been established.
The Vpr protein of human immunodeficiency virus type 1 influences nuclear localization of viral nucleic acids in nondividing host cells.
TLDR
Redundant nucleophilic determinants of HIV-1 that independently permit nuclear localization of viral nucleic acids and virus replication in nondividing cells such as monocyte-derived macrophages are demonstrated.
The glucocorticoid receptor type II complex is a target of the HIV-1 vpr gene product.
TLDR
Together these data directly link the activity of the vpr gene product to the glucocorticoid steroid pathway and provide a biochemical mechanism for the cellular and viral activity of Vpr, as well as suggest that a unique class of antivirals, which includes mifepristone (RU486), may influence HIV-1 replication.
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