Wmjm. Bogers et al., Characteristics of primary infection of a European human immunodeficiency virus type 1 clade B isolate in chimpanzees, J GEN VIROL, 79, 1998, pp. 2895-2903
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.