HIV: from discovery to uncovering features of pathogenesis and long-term survival.
Int Conf AIDS 1994 Aug 7-12; 10:6 (abstract no. TS2) Levy JA; Cancer Research Institute, School of Medicine, Univ. of California, San Francisco 94143-0128.
The discovery of HIV over ten years ago sparked research efforts that uncovered many properties of the virus that could influence pathogenesis. Its heterogeneous features, reflected by cellular tropism, replication kinetics, cytopathicity, and sensitivity to antiviral antibodies, have helped to distinguish strains that destroy the immune system and those associated with disease in the brain and bowel. Alterations in the viral genome over time depend on the extent of HIV replication and consequent mutation. HIV evolution in the host appears to occur selectively in certain organs and can be linked to pathogenesis. This viral heterogeneity has been associated with progression to disease and selective transmission, particularly from mother to child. The major immune response, mediated by CD8+ cells, can act early in infection and suppress the emergence of viral variants with different pathogenic potential. This anti-HIV activity can reduce viral load, prevent superinfection and control HIV production for long periods of time. The CD8+ cell antiviral response is enhanced by Th1 type cytokines (e.g. IL-2) and inhibited by Th2 type cytokines (e.g. IL-10). The reduction caused by Th2 cytokines can be reversed by the Th1 cytokines. This antiviral activity can be demonstrated in the blood as well as in lymph nodes of asymptomatic individuals. Its mechanism appears to be via a novel cytokine, CAF, that arrests transcription via the viral LTR. A model for evaluating this pathogenic pathway has recently been developed in the baboon infected with HIV-2. Viremia, CD8+ cell antiviral responses and pathologic conditions including lymphoid lysis, lymphocytic interstitial pneumonia and fibromatosis have been demonstrated. These observations on virus-host interactions provide insights into the steps involved in HIV infection and pathogenesis. They could lead to new approaches for assuring long term survival for all infected individuals.
Keywords: AEGIS, HIV, HIV Infections, Virus Replication, HIV-2, Viral Load, HIV Long-Term Survivors, HIV Long Terminal Repeat, Antigens, CD8, Viremia, HIV Core Protein p24, Cytokines, HIV Envelope Protein gp120, Interleukin-10, Interleukin-2, Survival, Child, Human, mortality, virology, genetics, ICA10
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