Document 0190
 DOCN  M9590190
 TI    HIV and long-term survival.
 DT    9509
 AU    Levy JA; Cancer Research Institute, University of California, San;
       Francisco, USA.
 SO    Annu Conf Australas Soc HIV Med. 1994 Nov 3-6;6:85 (unnumbered
       abstract). Unique Identifier : AIDSLINE ASHM6/95291909
 AB    HIV-1 and HIV-2, the causative agents of AIDS, consist of a wide variety
       of viral strains which differ in their biologic, serologic, and
       molecular properties. These viruses can be distinguished by the cells
       they infect, how well they replicate, whether they kill the cells
       infected, and how sensitive they are to antibody neutralization or
       enhancement. Moreover, their genomes can be distinguished by molecular
       characteristics. Distinct features of each virus have been associated
       primarily with variations in the envelope and regulatory genes. In this
       regard, cellular host range and cytopathology appear determined by the
       conformation of the envelope primarily and not by specific linear
       epitopes. A similar conclusion on envelope conformation was shown
       recently with monoclonal antibodies against specific viral subtypes in
       terms of antibody-mediated neutralization and enhancement. Each
       replicative cycle of the virus can lead to up to ten mutations (many of
       them lethal) but eventually viruses emerge that can be more cytopathic
       or home out in different tissues, such as the brain and bowel. To
       prevent these mutations, the host immune response, both humoral and
       cellular, is important. Antibodies that neutralize HIV can prevent
       infection by free virus. Cellular immunity attacks virus-infected cells
       and can be mediated by NK cells, macrophages, and CD8+ lymphocytes. The
       CD8+ cells can have cytotoxic anti-cellular immune responses, or show
       the ability to suppress HIV replication in infected cells. Our
       laboratory has focused on the latter function of these cells and has
       demonstrated that the CD8+ cells' ability to inhibit virus replication
       is associated with an asymptomatic state and long-term survival. With
       development of symptoms, the ability of CD8+ cells to suppress virus is
       markedly decreased. This antiviral response is mediated by a novel CD8+
       cell antiviral factor (CAF) that appears to block RNA transcription.
       This antiviral response can be noted early in acute infection before
       neutralizing antibodies are detected. Furthermore, this anti-HIV
       response appears to be one of the first to decrease prior to the loss of
       CD4+ cells and progression to disease. Thus, attempts to increase or
       maintain this cellular immune response is a major direction in HIV
       research. We have noted that certain cytokines, particularly those of
       the TH1 type (e.g., IL2, IFN-gamma), enhance CD8+ cell antiviral
       responses, whereas TH2 type cytokines (e.g., IL4, IL10) can inhibit the
       activity. TH1 cytokines can counter the effects of the TH2 cytokine on
       the CD8+ cell response. This observation offers some hope for
       therapeutic intervention. The directions for maintaining long-term
       survival (characterized by low virus yields and an asymptomatic state)
       are increasing TH1-type cytokines within the host, and the strong CD8+
       cell antiviral responses with substantial levels of CAF production. By
       achieving this objective, all infected individuals could maintain a
       long-term asymptomatic state.
 DE    Cytokines/PHYSIOLOGY  Cytotoxicity, Immunologic/IMMUNOLOGY  CD4-Positive
       T-Lymphocytes/IMMUNOLOGY  CD8-Positive T-Lymphocytes/IMMUNOLOGY
       Disease-Free Survival  Human  HIV Infections/IMMUNOLOGY/*MORTALITY
       *HIV-1/IMMUNOLOGY  *HIV-2/IMMUNOLOGY  Survival Analysis  Virus
       Replication/IMMUNOLOGY  MEETING ABSTRACT

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).