AEGiS-12IAC: Evolutionary fate of a molecularly cloned simian-human immunodeficiency virus in vivo: the envelope gene.

12th International AIDS Conference


Geneva, Switzerland - June 28-July 3, 1998

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Evolutionary fate of a molecularly cloned simian-human immunodeficiency virus in vivo: the envelope gene.

Int Conf AIDS 1998 Jun 28-Jul 3; 12:26 (abstract no. 11219)

Bernardin F, Beyer C, Gloeckler L, Gut JP, Einius S, Kirn A, Aubertin AM
Unite Inserm 74-Institute de Virologie, Strasbourg, France.

BACKGROUND: Chimeric lentiviruses (SHIV) composed of SIVmac239 (gag, pol, vif, vpr and vpx) and HIV (env, tat, rev and vpu) have become relevant to mimic HIV infection in non human primates. To validate this model, we characterized virological and immunological markers during infection of macaques.

METHODS: Three Chinese rhesus macaques and two cynomolgus monkeys were inoculated intravenously with SHIVsbg constructed with HIV-1 Lai genes. During the period of follow-up, the cellular viral load, the pattern of antibody recognition of linear epitopes encompassed in the V3-V5 Env region were determined as well as its influence on the genetic variability.

RESULTS: After an initial peak at two weeks post-infection (w.p.i.), the cellular viral load dropped to values near 0-1 infected cell per million from 22-43 w.p.i. The analysis of the antibody response demonstrated a strong recognition of the V3 loop, while limited in the CT part of C4. Nucleotide sequence of the V3-V5 region revealed a mean variability of 0.22% with a predominance of transitions. The dNS/dS ratio is low for rhesus macaques and shows an increase with time in cynomolgus monkeys. The mean frequency of peptide changes is 0.37% with a fluctuating dNC/dC ratio. Moreover, mutations are essentially localized in the C3 and C4 parts, the latter including the CD4-binding domain.

CONCLUSION: These results highlight the low variability of the SHIVsbg in vivo and the limited heterogeneity of variable regions. Of these, the V3 loop apex is well conserved. This study also indicates that the macaque and human immune systems recognize similar linear 13-cell epitopes on envelope glycoprotein.

Keywords: AEGIS, Lentiviruses, Primate, HIV-1, Viral Load, HIV Infections, Macaca mulatta, Macaca fascicularis, Base Sequence, Cloning, Organism, Animal, Human, genetics, ICA12KWDaegis,lentiviruses,primate,hiv-1,viralload,hivinfections,macacamulatta,macacafascicularis,basesequence,cloning,organism,animal,human,genetics,ica12
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Copyright © 1998 - International AIDS Society (IAS). Reproduction of this abstract (other than one copy for personal reference) must be cleared through the IAS.