Emergence of a highly pathogenic simian/human immunodeficiency virus in a rhesus macaque treated with anti-CD8 mAb during a primary infection with a nonpathogenic virus

摘要

Although simian/human immunodeficiency virus (SHIV) strain DH12replicates to high titers and causes immunodeficiency in pig-tailedmacaques, virus loads measured in SHIVDH12-infected rhesusmonkeys are consistently 100-fold lower and none of 22 inoculatedanimals have developed disease. We previously reported that theadministration of anti-human CD8 mAb to rhesus macaques at the time ofprimary SHIVDH12 infection resulted in marked elevations ofvirus loads. One of the treated animals experienced rapid and profounddepletions of circulating CD4+ T lymphocytes. Although theCD4+ T cell number partially recovered, this monkeysubsequently suffered significant weight loss and was euthanized. Atissue culture virus stock derived from this animal, designatedSHIVDH12R, induced marked and rapid CD4+ cellloss after i.v. inoculation of rhesus monkeys. Retrospective analysesof clinical specimens, collected during the emergence ofSHIVDH12R indicated: (i) the input clonedSHIV remained the predominant virus during the first 5–7 months ofinfection; (ii) variants bearing only a few of theSHIVDH12R consensus changes first appeared 7 months afterthe administration of anti-CD8 mAb; (iii) high titers ofneutralizing antibody directed against the input SHIV were detected byweek 10 and persisted throughout the infection; and (iv)no neutralizing antibody against SHIVDH12R ever developed.