Genetic characterization of near full length SIVdrl genomes from four captive drills (Mandrillus leucophaeus).

We sequenced near full length SIVdrl genomes from four captive drills (Mandrillus leucophaeus). All four animals were born in captivity in German zoos. Although serologically SIV negative before acquisition in zoo A in 2008 and 2009, during a routine analysis all four animals were determined to be SIV antibody positive in 2011. Comparisons of the four new SIVdrl sequences showed high identity among each other (90.7-97.7% in env) and to the only published full length sequence SIVdrl FAO (90.5-92.8% in env), which is also derived from a captive drill. SIVdrl infections seem to be highly prevalent in captive drills, probably resulting from frequent animal transfers between the zoos in an effort to maintain this highly endangered species and its genetic diversity. This should be kept in mind as SIVdrl may be transmitted to uninfected animals in open groups and potentially also to animal keepers having contact with these nonhuman primates.

Mimotopes selected with antibodies from HIV-1-neutralizing long-term non-progressor plasma.

A promising approach to identify HIV-1 vaccine candidates is to dissect the natural immune response against the virus in persons controlling the infection over decades without any antiviral therapy. Here we focus on a group of such persons, eight long-term non-progressors (LTNP), in which we proved the presence of broadly neutralizing antibodies against HIV-1 in the plasma as very likely cause for their LTNP status. The aim of this study was to identify the epitopes for these neutralizing antibodies, as these should represent immunogens potentially able to elicit neutralizing antibodies upon vaccination. We screened random peptide phage libraries with plasma antibodies from eight LTNP. After several rounds of positive and negative selection, about 700 HIV-specific mimotopes were sequenced. The mimotope sequences were analyzed for homology to HIV-1 Env, in particular for their capacity to represent conformational epitopes on the surface of the gp120 structure using our software 3DEX. Related phage groups were analyzed for crossreactivity with the LTNP plasma by ELISA as well as for their capacity to induce HIV-1-neutralizing antibodies in mice. Based on this study interesting mimotopes can now be selected for further immunization studies.

Genetic and biological characterization of recombinant HIV type 1 with Env derived from long-term nonprogressor (LTNP) viruses.

Multiple factors are known to contribute to nonprogressive disease in long-term nonprogressors (LTNP). We previously selected LTNPs, in which broadly neutralizing antibodies against HIV-1 very likely contribute to disease prevention. Here, we characterize those LTNPs further. We analyzed sequences of the viral genes env, nef, vpr, tat, and rev as well as the cellular ccr5, HLA-B*5701, and HLA-B*27 genes derived from eight LTNPs, as mutations in these genes have been associated with the LTNP status in some studies. Furthermore, we compared the replication rates of recombinant reporter viruses carrying envelope proteins from LTNPs to control viruses from patients with similar CD4 count and viral load. Concerning the cellular factors, none of the eight LTNPs showed the 32-base pair deletion in the ccr5 gene, and HLA-B*5701 and HLA-B*27 alleles were detected in only one LTNP, respectively. The reading frames for the regulatory genes nef, vpr, tat, and rev were all open. Although Env sequences from LTNPs differed from those of control patients with respect to the length of variable domains and the number of N-glycosylation sites, these differences were not statistically significant and did not lead to differences in infectivity of recombinant reporter viruses.