Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees

The aim of the study was to select, from a panel of candidate European huma n immunodeficiency virus type 1 (HIV-1) clade B primary virus isolates, one isolate based on replication properties in chimpanzee peripheral blood mon onuclear cells (PBMC). Secondly, to evaluate the in vivo kinetics of primar y infection of the selected isolate at two different doses in two mature, o utbred chimpanzees (Pan troglodytes). Four different low passage, human PBM C-cultured 'primary' HIV-1 isolates with European clade B consensus sequenc e were compared for their ability to replicate in vitro in chimpanzee versu s human PBMC. The isolate which yielded the highest titre and most vigorous cytopathic effect in chimpanzee PBMC was evaluated for coreceptor usage an d chosen for evaluation in vivo. Only the HIV-1(Han2) isolate replicated in chimpanzee PBMC in vitro at detectable levels. This isolate was demonstrat ed to utilize CCR4, CCR5 and CXCR4 coreceptors and could be inhibited by be ta-chemokines. Infection of chimpanzees was demonstrated by viral RNA and D NA FCR analysis, both in plasma as well as in PBMC and lymph node cells as early as 3 weeks after inoculation. Antibodies developed within 6 weeks and continued to increase to a maximum titre of approximately 12800, thereafte r remaining in this range over the follow-up period of 2 years. Compared to cell line-adapted HIV-1 isolates there were slight but no dramatic differe nces in the kinetics of infection of chimpanzees with this particular prima ry isolate.