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

  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},
  • 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… 
Human immunodeficiency virus type 1 Vpr: functions and molecular interactions.
Study of the interactions between Vpr and cellular proteins may help to understand the mechanism(s) of HIV-1 pathogenicity, and some possible roles proposed for this protein are described.
HIV-1 Vpr Induces Adipose Dysfunction in Vivo Through Reciprocal Effects on PPAR/GR Co-Regulation
A pathogenic role is investigated for the HIV-1 accessory protein viral protein R (Vpr), which can coactivate the glucocorticoid receptor (GR) and co-repress peroxisome proliferator–activated receptor γ (PPARγ) in vitro, in HIV-associated adipose dysfunction.
HIV-1 Infection Alters Gene Expression in Adipose Tissue, Which Contributes to HIV-1/Haart-Associated Lipodystrophy
A role of HIV-1 infection itself in eliciting adipose tissue alterations that are worsened by HAART, which ultimately leads to HALS is indicated.
Pathogenesis and Treatment of HIV Infection: The Cellular, the Immune System and the Neuroendocrine Systems Perspective
An up-to-date overview of HIV-host interactions at the cellular, the immune system and the neuroendocrine systems level is provided and it is suggested that the causal relationships between the complex sets of viral and immunological processes that contribute to protection or disease pathogenesis are still poorly understood.
Differential Regulation of host cellular gene expression by HIV-1 Viral protein R (Vpr): Implications for host cell function
A molecular basis for changes induced in the host cell by HIV-1 Vpr is presented and two potential pathways for the design of anti-retroviral therapeutics targeting HIV- 1 Vpr are elucidated.
Allopregnanolone and neuroHIV: Potential benefits of neuroendocrine modulation in the era of antiretroviral therapy
The clinical and preclinical evidence for neuroendocrine dysfunction in HIV, the capacity for hormone therapeutics to play an ameliorative role and the future steroid‐based therapeutics that may have efficacy as novel adjunctives to cART are reviewed.
AIDS/HPA Axis - Endotext - NCBI Bookshelf
This chapter discusses interaction between AIDS/HIV and the HPA axis, a major machinery coordinating adaptive response to stress with the 3 components, brain hypothalamus, pituitary gland and adrenal cortex, and its endeffectors glucocorticoids, which is reviewed and discussed.
Immunoendocrine Interactions during HIV-TB Coinfection: Implications for the Design of New Adjuvant Therapies
The use of adrenal hormones and their derivatives in immune-therapy and the use of some of these compounds like the adjuvant for the prevention and treatment of TB in HIV patients are evaluated.
Cardiovascular Risk in Patients with HIV Infection
Important clinical aspects of treating middle-aged HIV-positive patients who have an increased risk of experiencing a cardiovascular event are discussed, including blood pressure and the influence of the individual drugs on blood pressure.
Lipodystrophy in HIV 1-infected patients: lessons for obesity research
The recognition of a local pro-inflammatory environment in lipoatrophic adipose tissue from affected patients, including macrophage infiltration and enhanced expression of chemokines and cytokines, points to events paradoxically similar to those in the hypertrophied adipose tissues in obesity.


AIDS-related lipodystrophy/insulin resistance syndrome.
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?
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
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
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.
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.
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.
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.
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.