       Document 0701
 DOCN  M9620701
 TI    Therapeutic approaches to HIV infection based on virus structure and the
       host pathogen interaction.
 DT    9602
 AU    Pauza CD; Streblow DN; Department of Pathology and Laboratory Medicine,
       University of; Wisconsin, Madison 53706, USA.
 SO    Curr Top Microbiol Immunol. 1995;202:117-32. Unique Identifier :
       AIDSLINE MED/96004232
 AB    The HIV-1 infection of central nervous system, with attendant neuropathy
       and dementia, poses a unique challenge for antiviral therapy. For
       practical considerations, it is important to define carefully the
       precise therapeutic objectives. (1) Is it necessary to inhibit spreading
       HIV-1 infection in the central nervous system? (2) What is the role of
       inflammatory responses in central nervous system disease during HIV-1
       infection? (3) Is there a correlation between pathology and dementia?
       (4) Are virions or virus gene products toxic in the central nervous
       system? (5) Is there a role for immune suppression and opportunistic
       pathogens in AIDS dementia? The development of therapeutic agents for
       HIV-1 infection is guided by our knowledge of virus structure, the
       function of viral proteins, the interactions with host components, and
       detailed features of the virus life cycle. In each case, unique features
       of the virus can be identified and established as targets for unique
       antiviral compounds. Drugs acting as inhibitors of virus enzymatic
       functions are plagued by the rapid development in vivo of drug-resistant
       virus variants, although combination or alternating chemotherapeutic
       regimens may obviate some of these concerns. Novel approaches to
       inhibiting virus are flourishing. In vitro studies show the value of
       agents as diverse as molecular decoys for tat activity to efforts to
       mutagenize integrated proviruses by modified oligonucleotides that form
       triple helices with chromosomal genes. As each particular clinical
       situation is better defined, the design and application of these agents
       can be refined to inhibit HIV-1 replication and reduce the associated
       morbidity.
 DE    Antiviral Agents/*THERAPEUTIC USE  Biological Response
       Modifiers/*THERAPEUTIC USE  Cyclosporine/THERAPEUTIC USE  Drug Design
       Drug Resistance, Microbial  Gene Products, rev/GENETICS/THERAPEUTIC USE
       Human  HIV/*DRUG EFFECTS/PATHOGENICITY/ULTRASTRUCTURE  HIV
       Infections/*DRUG THERAPY/THERAPY  HIV Protease Inhibitors/THERAPEUTIC
       USE  RNA-Directed DNA Polymerase/DRUG EFFECTS  Variation (Genetics)
       Virion/DRUG EFFECTS  JOURNAL ARTICLE  REVIEW  REVIEW, TUTORIAL

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

