Conserved and exposed epitopes on intact, native, primary human immunodeficiency virus type 1 virions of group M

We have examined the exposure and conservation of antigenic epitopes on the surface envelope glycoproteins (gp120 and gp41) of 26 intact, native, prim ary human immunodeficiency virus type 1 (HIV-1) group hi virions of clades A to H. For this, 47 monoclonal antibodies (MAbs) derived from HIV-1-infect ed patients were used which were directed at epitopes of gp120 (specificall y V2, C2, V3, the CD4-binding domain [CD4bd], and C5) and epitopes of gp41 (clusters I and II). Of the five regions within gp120 examined, MAbs bound best to epitopes in the V3 and C5 regions. Only moderate to weak binding wa s observed by most MAbs to epitopes in the V2, C2, and CD4bd regions. Two a nti-gp41 cluster I MAbs targeted to a region near the tip of the hydrophili c immunodominant domain bound strongly to >90% of isolates tested. On the o ther hand, binding of anti-gp41 cluster II MAbs was poor to moderate at bes t. Binding was dependent on conformational as well as linear structures on the envelope proteins of the virions. Further studies of neutralization dem onstrated that MAbs that bound to virions did not always neutralize but all MAbs that neutralized bound to the homologous virus. This study demonstrat es that epitopes in the V3 and C5 regions of gp120 and in the cluster I reg ion of gp41 are well exposed on the surface of intact, native, primary HIV- I isolates and that cross-reactive epitopes in these regions are shared by many viruses from clades A to H. However, only a limited number of MAbs to these epitopes on the surface of HIV-1 isolates can neutralize primary isol ates.