This interaction leads to conformational rearrangements in gp120 forming or revealing CD4 induced (CD4i) epitopes which are critical for the subsequent recognition of the co-receptor required for viral entry. The

CD4-bound state of gp120 has been considered a potential immunogen for HIV-1 vaccine development. Here we report on an alternative means to induce gp120 into the CD4i conformation.

Results: Combinatorial phage display peptide libraries were screened against HIV-1 gp120 and short (14aa) peptides were selected that bind the viral envelope and allosterically induce the CD4i conformation. The lead peptide was subsequently systematically optimized for higher affinity as well as more efficient inductive activity. The peptide: gp120 complex was scrutinized with a panel of neutralizing anti-gp120 monoclonal antibodies and CD4 itself, illustrating that peptide binding does not interfere with or obscure the CD4 binding site.

Conclusions: Two apoptosis inhibitor click here surfaces of gp120 are considered targets for the development of cross neutralizing antibodies against HIV-1; the CD4 binding site and CD4i epitopes. By implementing novel peptides that allosterically induce the CD4i epitopes we have generated a viral envelope that presents both of these surfaces simultaneously.”
“Background: Following mucosal human immunodeficiency virus

type 1 (HIV-1) transmission, type 1 interferons (IFNs) are rapidly induced at sites of initial virus replication in the mucosa and draining lymph nodes. However, the role played by IFN-stimulated antiviral activity in restricting HIV-1 replication during the initial stages of infection is not clear. We hypothesized AZD1480 in vitro that if type 1 IFNs exert selective pressure on HIV-1 replication in the earliest stages of infection, the founder viruses that succeed in establishing systemic infection would be more IFN-resistant than viruses replicating during chronic infection, when type 1 IFNs are produced at much lower levels. To address this hypothesis, the relative resistance of virus isolates

derived from HIV-1-infected individuals during acute and chronic infection to control by type 1 IFNs was analysed.

Results: The replication of plasma virus isolates generated from subjects acutely infected with HIV-1 and molecularly cloned founder HIV-1 strains could be reduced but not fully suppressed by type 1 IFNs in vitro. The mean IC50 value for IFNa2 (22 U/ml) was lower than that for IFN beta (346 U/ml), although at maximally-inhibitory concentrations both IFN subtypes inhibited virus replication to similar extents. Individual virus isolates exhibited differential susceptibility to inhibition by IFNa2 and IFN beta, likely reflecting variation in resistance to differentially up-regulated IFN-stimulated genes. Virus isolates from subjects acutely infected with HIV-1 were significantly more resistant to in vitro control by IFNa than virus isolates generated from the same individuals during chronic, asymptomatic infection.