       Document 0805
 DOCN  M9460805
 TI    Modulation of the effector function of human monocytes for Mycobacterium
       avium by human immunodeficiency virus-1 envelope glycoprotein gp120.
 DT    9404
 AU    Shiratsuchi H; Johnson JL; Toossi Z; Ellner JJ; Department of Medicine,
       Case Western Reserve University,; University Hospitals, Cleveland, Ohio.
 SO    J Clin Invest. 1994 Feb;93(2):885-91. Unique Identifier : AIDSLINE
       MED/94157110
 AB    Disseminated Mycobacterium avium infection in AIDS is associated with
       high tissue burdens (10(9)-10(10) mycobacteria/g tissue) of organism.
       The basis for the extraordinary susceptibility of AIDS to M. avium
       infection is unclear. HIV or its constituents may alter mononuclear
       phagocyte functions resulting in enhanced intracellular M. avium growth.
       The effects of an envelope glycoprotein (gp120), a transmembrane protein
       (p121), and core proteins of HIV-1 on M. avium infection of human
       monocytes were examined. Preculturing monocytes with gp120 inhibited M.
       avium phagocytosis and consistently enhanced intracellular growth of six
       M. avium strains. Pretreatment with p121, gag5, or p24 did not inhibit
       phagocytosis nor enhance intracellular growth of M. avium. Incubation of
       gp120 with soluble CD4 before addition to monocyte cultures or
       pretreatment of monocytes with OKT4A abrogated gp120 effects on M. avium
       phagocytosis and intracellular growth. gp120 also augmented cytokine
       production by infected monocytes. These results suggest that gp120, but
       not p121 or core proteins, modulate monocyte phagocytosis and enhance
       intracellular growth of M. avium at least in part through monocyte CD4
       receptors. Direct effects of HIV-1 products may, therefore, contribute
       to the diathesis of AIDS to develop disseminated M. avium infection and
       to the extensive replication of the organisms within tissue macrophages.
 DE    Antibodies, Monoclonal/PHARMACOLOGY  Antigens, CD/METABOLISM  Antigens,
       CD4/METABOLISM  AIDS-Related Opportunistic Infections/PHYSIOPATHOLOGY
       Cells, Cultured  Disease Susceptibility  Dose-Response Relationship,
       Drug  Human  HIV Envelope Protein gp120/*PHARMACOLOGY  HIV
       Seronegativity  HIV-1/*PHYSIOLOGY  Monocytes/DRUG
       EFFECTS/*MICROBIOLOGY/PHYSIOLOGY  Mycobacterium avium/DRUG
       EFFECTS/*PHYSIOLOGY/PATHOGENICITY  Neutralization Tests
       Phagocytosis/DRUG EFFECTS  Recombinant Proteins/PHARMACOLOGY  Support,
       U.S. Gov't, P.H.S.  Tuberculosis/PHYSIOPATHOLOGY  Virulence/DRUG EFFECTS
       JOURNAL ARTICLE

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

