Therapeutic Strategies Employing CD4, the HIV Receptor

  • Per Ashorn
  • Bernard Moss
  • Edward A. Berger
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 312)


Infection of T-lymphocytes and macrophages by human immunodeficiency virus (HIV) is initiated by binding of the external subunit of the viral envelope glycoprotein (gp120) to CD4 molecules on the target cell membrane (1). Recombinant soluble forms of CD4 retain the capacity for high affinity binding to gp120 (2, 3, 4, 5, 6, 7), suggesting potential therapeutic uses of CD4 derivatives. The diverse concepts for exploiting the CD4/gp120 interaction for therapy are outlined in Figure 1. The initial concept was based on the finding that soluble truncated forms of CD4 (sCD4) are able to neutralize HIV infectivity in vitro (2, 3, 4, 5, 6) (Figure 1A). Several “second generation” applications of this neutralizing concept are under development, including attachment of the CD4 to immunoglobulin constant region sequences (8, 9, 10, 11, 12), or presentation of the CD4 in association with erythrocytes (13). These modifications provide the advantages of increased plasma half-life compared to sCD4, and possibly enhanced efficiency of neutralization due to multivalency. Recent findings indicate that sCD4 is capable of “stripping” gp120 from the envelope glycoprotein complex (14, 15, 16), suggesting that the mechanism of sCD4 neutralization of HIV infectivity might involve more than simple competition for gp120 binding to CD4 on the surface of the target cell.


Human Immunodeficiency Virus Human Immunodeficiency Virus Type Human Immunodeficiency Virus Infection Envelope Glycoprotein Human Immunodeficiency Virus Replication 
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Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • Per Ashorn
    • 1
  • Bernard Moss
    • 1
  • Edward A. Berger
    • 1
  1. 1.Laboratory of Viral DiseasesNational Institute of Allergy and Infectious Diseases National Institutes of HealthBethesdaUSA

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