Cytokine Cascades in HIV Infection

  • Guido Poli
  • Anthony S. Fauci


Since the recognition of human immunodeficiency virus type 1 (HIV-1) as the causative agent of the acquired immunodeficiency syndrome (AIDS), the search to unravel the viral and cellular factors controlling its replicative ability has become an important goal of both basic and applied research. Cellular transcription factors, such as NF-κB, as well as viral proteins may activate HIV transcription in cells latently infected with HIV. In this regard, certain studies indicate that latent infection is the predominant virological state of infected cells in vivo (Embretson et al., 1993), although a fraction of cells express virus in lymphoid organs throughout the entire course of disease (Pantaleo et al., 1993). In addition, plasma viremia can be detected throughout the entire course of HIV disease (Piatak et al., 1993). Furthermore, both HIV and CD4+ T lymphocytes (the predominant target of HIV infection) rapidly turn over, particularly in the advanced stages of HIV disease. This has been ascertained from studies on patients treated with antiretroviral agents, including nucleoside analogues and inhibitors of HIV protease that can dramatically, but transiently, decrease circulating HIV until drug-resistant strains repopulate the plasma compartment (Wei et al., 1995; Ho et al., 1995). However, residual virus invariably is unaffected by antiretroviral agents, at least those currently in use. An important component of this residual HIV burden is in the form of integrated proviruses that exist in the latent state and are refractory to agents such as zidovudine that affect the preintegration steps of HIV replication (Perno et al., 1989; Poli et al., 1989). Thus, understanding the regulatory mechanisms controlling HIV replication in infected cells that are not actively expressing virus will be critical for the development of strategies aimed at eliminating or at least curtailing virus spread in the host.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Virus Expression Cytokine Cascade Soluble Cytokine Receptor 
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Copyright information

© Springer Science+Business Media New York 1996

Authors and Affiliations

  • Guido Poli
    • 1
  • Anthony S. Fauci
    • 2
  1. 1.AIDS Immunopathogenesis UnitDIBIT, San Raffaele Scientific InstituteMilanItaly
  2. 2.Laboratory of ImmunoregulationNational Institute of Allergy and Infectious Diseases, National Institutes of HealthBethesdaUSA

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