Document 0198
 DOCN  M9440198
 TI    Viral multiplicity of attachment and its implications for human
       immunodeficiency virus therapies.
 DT    9404
 AU    Spouge JL; National Center for Biotechnology Information, National
       Library; of Medicine, Bethesda, Maryland 20894.
 SO    J Virol. 1994 Mar;68(3):1782-9. Unique Identifier : AIDSLINE
       MED/94149872
 AB    The multiplicity of attachment (MOA) of a virion in any particular time
       interval is the average number of cellular attachment opportunities that
       must be blocked to keep the virion in suspension. MOA is usually
       proportional to incubation time and cell concentration. Low MOA (like
       low multiplicity of infection) is required for reproducible assay of
       adsorptive blockers, and high MOA by itself can produce spurious
       synergies between adsorptive blockers, e.g., soluble CD4 (sCD4) and some
       antibodies. Poliovirus and human immunodeficiency virus (HIV) data show
       that viral neutralization conforms quantitatively to MOA and kinetic
       theory over large ranges of incubation times and target cell
       concentrations. Extrapolating sCD4 data beyond conditions achievable in
       vitro to those in vivo predicts that sCD4 concentrations above the
       strain-specific sCD4-gp120 dissociation constant are required to block
       lymphoid HIV significantly, in at least semiquantitative agreement with
       clinical results. The extrapolation is applicable to humoral
       neutralization data as well. MOA analysis also indicates that although
       completely stopping the attachment of individual virions to cells may
       still be an effective therapeutic strategy against established HIV
       infection, merely retarding attachment probably is not. The concept of
       MOA holds great promise for improving the therapeutic relevance of in
       vitro data and can be applied to any infectious agent, to many processes
       that impair or enhance infection steps, and to many assay end points,
       not just infection.
 DE    Antigens, CD4/METABOLISM/PHARMACOLOGY  Dose-Response Relationship, Drug
       Human  HIV/DRUG EFFECTS/*GROWTH & DEVELOPMENT/PATHOGENICITY  HIV
       Envelope Protein gp120/METABOLISM  HIV Infections/*DRUG THERAPY
       *Models, Theoretical  Neutralization Tests  Polioviruses/DRUG
       EFFECTS/GROWTH & DEVELOPMENT/PATHOGENICITY  Protein Binding  JOURNAL
       ARTICLE

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