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

Although simian/human immunodeficiency virus (SHIV) strain DH12 replicates to high titers and causes immunodeficiency in pig-tailed macaques, virus lo ads measured in SHIVDH12-infected rhesus monkeys are consistently 100-fold lower and none of 22 inoculated animals have developed disease. We previous ly reported that the administration of anti-human CD8 mAb to rhesus macaque s at the time of primary SHIVDH12 infection resulted in marked elevations o f virus loads. One of the treated animals experienced rapid and profound de pletions of circulating CD4+ T lymphocytes. Although the CD4(+) T cell numb er partially recovered, this monkey subsequently suffered significant weigh t loss and was euthanized. A tissue culture Virus stock derived from this a nimal, designated SHIVDH12R, induced marked and rapid CD4(+) cell loss afte r i.v, inoculation of rhesus monkeys. Retrospective analyses of clinical sp ecimens, collected during the emergence of SHIVDH12R indicated: (i) the inp ut cloned SHIV remained the predominant Virus during the first 5-7 months o f infection; (ii) Variants bearing only a few of the SHIVDH12R consensus ch anges first appeared 7 months after the administration of anti-CD8 mAb;(iii ) high titers of neutralizing antibody directed against the input SHIV were detected by week 10 and persisted throughout the infection; and (iv) no ne utralizing antibody against SHIVDH12R ever developed.